APCHG 2019 Proceedings

13th Asia Pacific Conference on Human Genetics
“Advancing Translational Medicine and Collaborations in Genomics”
EVENT PROCEEDINGS
The Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila,
with the support of various partners including the Newborn Screening Foundation, Inc , hosted and
organized the 13th Asia Pacific Conference on Human Genetics with the theme “Advancing
Translational Medicine and Collaborations in Genomics” on November 7-9, 2019 at the Makati
Shangri-La Manila. The presentations focused on the use of new knowledge in genomics into clinical
practice and to incorporate clinical observations and questions into generating further research in the
field of genetics and genomics.
The Asia-Pacific Conference on Human Genetics (APCHG) is a biennial conference hosted by member
countries of the Asia Pacific Society of Human Genetics (APSHG), of which the Philippines is a member.
The APSHG is a non-profit organization founded in 2006, comprising persons involved or interested in
the study of human genetics from all the major countries in the Asia-Pacific region.
Pre-conference workshops were as follows: (1) Wellcome Genome Campus Advanced Course on Next
Generation Sequencing Analysis for Genetic Diseases; (2) Third Genetic Counseling Workshop
coorganized with the Professional Society of Genetic Counselors in Asia: (3) Thalassemia Workshop
for Newborn Screening Implementers co-organized with the Newborn Screening Reference Center;
and the (4) 4th ASEAN Congress on Medical Biotechnology and Molecular Biosciences on Emerging
Issues on Hemoglobinopathies in the Asia Pacific Region. Furthermore, the importance of training the
next generation geneticists and genetic counselors was highlighted in the iGNiTE sessions (Genomic
Networking and Training with the Experts) during the second and third day of the main conference
where students and trainees discussed undiagnosed genetic and metabolic cases with the experts.
These conferences and workshops brought together an outstanding community of faculty, scientists,
researchers, and students from the Asia-Pacific region and different parts of the world and tackled
important developments in genetics and genomics in health.
Meaningful collaborations were made among colleagues in the region and worldwide. The main
conference had a total of 554 attendees of which 52% (287) were foreign delegates and 48% (267)
were local delegates, composed mainly of scientists, clinical geneticists, genetic counselors and
students. The foreign delegates are from 25 countries, namely:Australia, Austria, Canada, China,
Finland, France, Greece, Hong Kong, India, Indonesia, Italy, Japan, Malaysia, Netherlands, Qatar,
Russia, Saudi Arabia, Singapore, South Korea, Sri Lanka, Taiwan, Thailand,United Arab Emirates, USA
and Vietnam.
http://www.apchg2019.org
Program at a glance
November 7, 2019 November 8, 2019 November 9, 2019
7:30AM-8:00AM 7:30AM-8:30AM 7:30AM-8:30AM
Registration iGNiTE Sessions: Genomic Networking and Training iGNiTE Sessions: Genomic Networking and Training
with the Experts (Undiagnosed Interesting Cases) with the Experts (Skeletal dysplasias)
8:00AM-9:30AM 8:30AM-10:00AM 8:30AM-9:15AM
Opening Ceremonies Simultaneous Symposia Plenary Session 6
9. Elucidating the Genetics of Complex Diseases: Where Comprehensive application of multi-omic approaches
Are We Now? for the genetic elucidation of “rare diseases”
10. Understanding Future Trends of Metagenomics,
Proteomics and Metabolomics
11. Solving the Brain Enigma: The Value of Genomics in
Neurpsychiatric Disorders
12. Disorders of Sexual Development: Integrating
Clinical and Genetic Approaches
9:30AM-10:00AM 10:00AM-10:30AM 9:15AM-10:00AM
Opening of Exhibits Coffee Break Plenary 7
Coffee Break Visit to Exhibits Gearing Up for the Phenomics Era
10:00AM-11:00AM 10:30AM-12:00PM 10:00AM-11:00AM
Keynote Plenary Simultaneous Symposia Poster Session 3
Two Tales of Translational Genomics: Pediatric Genetics 13. Improving the Landscape of LSD Care through Coffee Break
and Inherited Breast and Ovarian Cancer diagnosis and therapeutics Visit to Exhibits
14. OMICS Technologies for optimized and personalized
medicine
15. Illumina Genomics Session
16. The Emerging Role of Enhancers in Gene Regulation
17. Inventing the future: MD-PhD’s researches on
spotlight
11:00AM-12:00PM 12:00PM-12:30PM 11:00AM-11:45AM
Plenary Session 2 Visit to Exhibits Closing Plenary
Organs on Chip: Advancing Therapies for Rare and Clinical and Ethical Implications of CRISPR Therapies
Complex Rare Diseases and Tools for Precision
Medicine
12:00PM-1:00PM 12:30PM-1:30PM 12:00PM-1:00PM
Perkin Elmer Luncheon Symposium Genzyme Luncheon Symposium Mead Johnson Luncheon Symposium
1:00PM-2:00PM 1:30PM-2:30PM 1:00PM-1:30PM
Poster Session 1 Visit to Exhibits Closing Ceremonies
Visit to Exhibits
2:00PM-3:30PM 2:30PM-3:30PM 3:00PM-6:00PM
Simultaneous Symposia Global Perspectives in Genomics and Medicine: An Tour of Intramuros: The Walled City (Ticketed Event)
1. Genetic Risk Assessment and Counselling in the Era APSHG-HUGO Plenary Session
of Genomics Precision Medicine: Making Sense of DNA Variants
2. Revolutionizing Newborn Screening: New Oncogenomics: Closing the Cancer Gap
Developments and New Dilemmas
3. Prenatal Genetics: How Genetic Technologies Are
Shaping Reproductive Decision-Making
4. ACMBMB Hemoglobinopathies: Advances in
Diagnosis and Innovative Therapeutics
3:30PM-4:00PM 3:30PM-4:15PM
Coffee Break Plenary Session 4
Visit to Exhibits Rare are Common: How Rare Diseases Reveal Molecular
Pathways for Common Disorders
4:00PM-5:30PM 4:15PM-5:00PM
Simultaneous Symposia Plenary Session 5
5. Advances in the Diagnosis and Therapy of Inherited Precision Public Health for Infectious Diseases in Asia
Metabolic Diseases
6. Discerning the Phenotypes of Genetic Disorders
Through Next Generation Sequencing
7. Patterns and Predictions of Genetic Migration in Asia
8. ACMBMB Hemoglobinopathies
6:00PM-7:30PM 5:00PM-7:00PM
APSHG Biennial Meeting (Members Only) Best Poster Presentations
Coffee Break and Visit to Exhibits
7:00PM-9:00PM
Fellowship Night
A. DETAILS OF THE CONFERENCE
Details of the conference sessions are listed below. There are two simultaneous sessions sponsored by PCHRD on
Day 2, namely SS 14: OMICS Technologies for optimized and personalized medicine; and SS 17: Inventing the future:
MD-PhDs' researches on spotlight. These simultaneous sessions highlighted and recognized the Filipino research
community, disseminated local research findings, and at the same time inspired young people to explore
opportunities for research in genetics and genomics.
Day 1 November 7, 2019

7:30AM - 8:30AM REGISTRATION
8:30AM - 9:30AM OPENING CEREMONIES
OPENING OF EXHIBITS
9:30AM- 10:00AM
COFFEE BREAK
10:00AM -11:00AM KEYNOTE PLENARY (Rizal Ballroom ABC)
Chair: Carmencita D. Padilla
Two Tales of Translational Genomics: Pediatric Genetics and Inherited Breast and Ovarian
Cancer
Mary-Claire King (USA)
11:00AM-12:00PM PLENARY SESSION 2 (Rizal Ballroom ABC)
Chair: Lai Poh San
Organs on Chip: Advancing Therapies for Rare and Complex Diseases and Tools for
Precision Medicine
Danilo A. Tagle (USA)
12:00PM-1:00PM LUNCHEON SYMPOSIUM INDUSTRY SPONSORED: PERKIN ELMER (Rizal Ballroom ABC)
Newborn Screening Pilot for duchenne muscular dystrophy (DMD) using GSP CK-MM kit as
first tier and NGS for confirmatory testing
Veronica Wiley (Australia)
1:00PM-2:00PM POSTER SESSION 1
VISIT TO EXHIBITS
SIMULTANEOUS SYMPOSIA (SS)
2:00PM-3:30PM SS 1: Genetic Risk Assessment and Counselling in the Era of Genomics
(Rizal Ballroom A)
Chair: Felicitas Lacbawan
Moderator: Peter James Abad
2:00PM – 2:20PM A: Genetic Counselling for Cancer: When Somatic Tumor Testing and Germline Mutations
Meet
Mercy Laurino (USA)
2:20PM -2:40PM B: Facilitating Cascade Family Testing: Challenges And Prospects in an Under Resource
Region
Breana Cham (Singapore)
2:40PM – 3:00PM C: Common Ethical Issues in Genetics and Genomics: A Clinic Based Experience
Stephen Lam (Hong Kong)
D: Establishing a statewide genetic counselors’ association through an iterative process
3:00PM-3:10PM Kunal Sanghavi (USA)
E: Reclassification of Variants of Unknown Significant (VUS): Impact on Clinical
Management and Genetic Counseling
3:10PM-3:20PM Rifhan Azwani Mazlan (Malaysia)
OPEN FORUM
3:20PM-3:30PM
2:00PM-3:30PM SS 2:Revolutionizing Newborn Screening: New Developments and New Dilemmas
(Rizal Ballroom B)
Chair: Meow-Keong Thong
Moderator: Leniza de Castro-Hamoy
2:00PM – 2:20PM A: Genomic Sequencing of Newborns

Carmencita D. Padilla (Philippines)
2:20PM -2:40PM B: Newborn Screening Beyond Metabolic Disorders: Successes and Challenges in
Introducing New Tests
2:40PM – 3:00PM C: Newborn Screening for LSDs: Current Status and Future Directions
Yin-Hsiu Chien (Taiwan)
D: Cystic fibrosis in Asia, an underestimated problem
3:00PM-3:10PM Gerard Pals (Netherlands)
E: Newborn Screening for Lysosomal Storage Disorders: Comparing Performance of
3:10PM-3:20PM Tandem Mass Spectrometry and Digital Microfluidics Platforms
Bradford Therrell (USA)
OPEN FORUM
3:20PM-3:30PM
2:00PM-3:30PM SS 3: Prenatal Genetics: How Genetic Technologies Are Shaping Reproductive Decision-
Making
(Rizal Ballroom C)
Chair: Benjamin Roa
Moderator: April Grace Berboso
2:00PM – 2:20PM A: Cytogenomic Array and Prenatal Applications: Diagnostic and Counselling Issues
Brian Chung (Hong Kong)
B: Prenatal Genetic Screening: Current Guidelines and Recommendations Juliana Lee
2:20PM -2:40PM (Malaysia)
C: What Not to Expect When You Are Expecting: Causes of Discordant NIPT Results
2:40PM – 3:00PM Kathleen A. Leppig (USA)
D: Clinical implementation of chromosomal microarray as a primary test for prenatal
diagnosis in Hong Kong
3:00PM-3:10PM Chung Claudia Ching Yan (Hong Kong)
E: Experiences of Chromosome Analysis Confirmation of NIPT for Numerical Chromosome
Abnormality in Indonesia
3:10PM-3:20PM Hannie Kartapradja (Indonesia)
OPEN FORUM
3:20PM-3:30PM
2:00PM-3:30PM SS 4: ACMBMB Hemoglobinopathies: Advances in Diagnosis and Innovative Therapeutics
(Pasay AB)
Chair: Carolyn Hoppe
Moderator: Catherine Lynn Silao
2:00PM – 2:20PM A: Novel Screening for Thalassemia by NGS
Chen Ping (China)
2:20PM -2:40PM B: Diagnosis and Classification of non-transfusion dependent thalassemias
Supachai Ekwattanakit (Thailand)
2:40PM – 3:00PM C: Gene Therapy for Thalassemia: Discoveries in the New Millennium
Suthat Fucharoen (Thailand)
3:00PM-3:20PM D: Global Globin 2020: Asian Perspective
Zilfalil Alwi (Malaysia)
3:20PM-3:30PM OPEN FORUM
COFFEE BREAK
3:30PM-4:00PM VISIT TO EXHIBITS
4:00PM-5:30PM SS 5: Advances in the Diagnosis and Therapy of Inherited Metabolic Diseases
(Rizal Ballroom A)
Chair: Veronica Wiley
Moderator: Mary Ann Abacan
4:00PM-4:20PM A: Inherited Small Molecule Disorders: Current and Future Therapies

Joy Lee (Australia)
4:20PM-4:40PM B: Treatable Inherited Disorders Revisited
MK Thong (Malaysia)
4:40PM-5:00PM C: Broadening the Phenotypes of Inherited Metabolic Diseases: New Discoveries Through
WES
John Christodoulou (Australia)
5:00PM-5:20PM D: Autologous transplantation with genetically edited stem cells for IEM: Pitfalls and
possibilities
Gerard Pals (Netherlands)
4:00PM-5:30PM SS 6: Discerning the Phenotypes of Genetic Disorders Through Next Generation Sequencing
(Rizal Ballroom B)
Chair: Yin-Hsiu Chien
Moderator: Maria Melanie Liberty Alcausin
4:00PM-4:20PM A: Whole Genome Sequencing in Severe Intellectual Disability
Christian Gilissen (Netherlands)
4:20PM-4:40PM B: Next Generation Sequencing: Efficient Tool for the Diagnosis of Rare Genetic Syndromes
Lai Poh San (Singapore)
C: Targeted Sequencing for Skeletal Dysplasia: Paving the Way for Gene Discoveries
4:40PM-5:00PM David Sillence (Australia)
D: Pre and Postanalytical Challenges of NGS: Time for Solutions
Felicitas Lacbawan (USA)
5:20PM-5:30PM
4:00PM-5:30PM SS 7: Patterns and Predictions of Genetic Migration in Asia
Chair: Maria Corazon de Ungria
Moderator: Kristin Grace Guerrero-Gonzalez
4:00PM-4:20PM A: Patterns of Genetic Admixture across the Indonesian Archipelago
Herawati Sudoyo (Indonesia)
4:20PM-4:40PM B: A Filipino Genomes Research Program: Representing the Underrepresented in Genomics
Research
Frederick C. Delfin (Philippines)
4:40PM-5:00PM C: Population Genetic structure in Malaysian Sub-ethnic Groups
5:00PM-5:20PM D: Population Genetics in China in the Context of Precision Medicine
Xu Shuhua (China)
4:00PM-5:30PM SS 8: ACMBMB Hemoglobinopathies
(Pasay AB)
Chair: Suthat Fucharoen
Moderator: Leslie Michelle Dalmacio
4:00PM-4:20PM A: Stem Cell-based Therapies in Thalassemias
Hai Yang Law (Singapore)
4:20PM-4:40PM B: Point of Care Testing for Hemoglobinopathies with focus on Thalassemias
Carolyn Hoppe (USA)
4:40PM-4:50PM C: Vienna Stripassays as an efficient tool for the detection of α and β Thalassemia
mutations
Robin Sandra Roch (Singapore)
4:50PM-5:00PM D: Alpha Beta Globin Gene Cluster Haplotypes of Thalassemia Patients in Indonesia – Are
they useful for population biomarkers?
Ita Margaretha Nainggolan (Indonesia)
5:00PM-5:10PM E: Diagnostic Yield for further investigation of cases with presence of HbH Inclusion Bodies
Wendy Meow Hong Low (Singapore)
OPEN FORUM
5:10PM-5:30PM
APSHG Biennial Meeting (Members only)
6:00PM-7:30PM
(Rizal A)
Keynote Plenary
Two Tales of Translational Genomics: Pediatric Genetics and Inherited Breast and Ovarian Cancer
Mary-Claire King (USA)

American Cancer Society Professor, Department of Medicine and the Department of Genomics
University of Washington
Genetics is a powerful way of thinking about the causes of human disease. In the past 20 years, with the
technological revolution in genomics, we now have the tools to answer the questions that people have been asking
since the dawn of genetics and before. I will discuss two quite different ways that genetics and genomics have
empowered physicians in the care of their patients. The first example will be our collaboration with Vietnamese
colleagues in the identification of genes responsible for severe congenital disorders in children, and the use of this
information in providing pre-gestational diagnosis to assure healthy future pregnancies. The second example will be
the story of the discovery and characterization of BRCA1 and her sister genes, and how gene discovery has been
translated into precision medicine and public health.
Plenary Session 2
Organs on Chip: Advancing Therapies for Rare and Complex Diseases and Tools for Precision Medicine

Associate Director for Special Initiatives, National Center for Advancing Translational Sciences
Approximately 30% of drugs have failed in human clinical trials due to adverse reactions despite promising
pre-clinical studies, and another 60% fail due to lack of efficacy. One of the major causes in the high attrition rate is
the poor predictive value of current preclinical models used in drug development despite promising pre-clinical
studies in 2-D cell culture and animal models. The NIH Microphysiological Systems (Tissue Chips) program led by
NCATS is developing alternative approaches and tools for more reliable readouts of toxicity and efficacy during drug
development. Tissue chips are bioengineered microphysiological systems utilizing human primary or stem cells
seeded on biomaterials manufactured with chip technology and microfluidics that mimic tissue histoarchitecture
and functional units of human organs. These platforms can be a useful tool for predictive toxicology and efficacy
assessments of candidate therapeutics. They can also be used to model disease states, providing new tools for the
understanding of disease mechanisms and pathologies, and assessing effectiveness of new therapies. By emulating
human physiology, these microfabricated devices are useful for modeling human diseases, for studies in precision
medicine and for use as “clinical trials on chips” to inform the design and conduct of human clinical studies. Effective
partnerships with stakeholders, such as regulatory agencies, pharmaceutical companies, patient groups, and other
government agencies is key to widesread adoption of this emerging technology.
Simultaneous Session 1
Genetic Risk Assessment and Counselling in the Era of Genomics
SS1-A
Genetic Counselling for Cancer: When Somatic Tumor Testing and Germline Mutations Meet
Mercy Y. Laurino (USA)

Seattle Cancer Care Alliance
The increasing application of routine tumor genomic profiling is critical to assess therapeutic options for
patients with cancer. The intent of this approach is to identify “driver” gene variants in specific cancer tissues and
thus providing patient access to “actionable” drugs during cancer treatment. Since tumor genomic profiling has been
routinely incorporated as part of a patient’s diagnostic workup, there is growing concern on the lack of
comprehensive pretest counseling to specifically discuss the possibility of discovering underlying germline
pathogenic variants. Published studies have noted that approximately 12% of tumor genomic profiling reports will
reveal an incidental germline pathogenic variant. The likelihood to identify such variants will only increase when a
patient’s personal and family history of cancer is already considered at high risk category. As such, a patient will
need to be aware during the pretest counseling session that a follow-up test may be indicated to further distinguish
between somatic and germline variants. It is also important to note that the recognition of these germline
pathogenic variants not only impacts the patient’s cancer care management and future surveillance, it also provides
the opportunity for cascade genetic testing in at-risk family members. Overall, the treating medical oncologist will
need to incorporate a much needed clinical service framework, in partnership with a cancer genetic counseling team,
for pretest counseling and post-test recommendations when ordering tumor genomic profiling tests.
SS 1-B
Facilitating Cascade Family Testing: Challenges And Prospects in an Under Resource Region
Breana Cham (Singapore)

Principal Genetic Counsellor
KK Women’s and Children’s Hospital
Genetic information is often thought of as personal information and is thought of as unique and identifying
of an individual. Such information, like the majority of our personal health data is thought to be confidential.
However, genetic variants are often shared by one or more family members. When a disease-causing variant is
identified in an individual, they are often counselled on the possibility of the same variant being found in blood
relatives. Cascade testing, or screening, is the practice of systematic testing of family members who are at risk of
inheriting a genetic variant previously identified in the proband. Being able to identify at-risk individuals has the
potential to benefit this population through early screening, medical surveillance or intervention and appropriate
genetic counselling. In spite of these benefits, clinicians face challenges in offering cascade testing. Some of the
barriers to uptake include lack of access to genetics services, financial and insurance considerations, limited
understanding of genetics and the perceived benefits of genetic information. Through achievable adjustments in
care provision, healthcare providers can play a part in overcoming some of these barriers and positively influence
the uptake and outcomes. A series of selected case studies will be used to illustrate the various ethical, social and
legal issues surrounding genetic counselling and genetic testing of extended families. Using these examples, common
considerations that need to be taken into account during the genetic counselling process and the potential barriers
in each situation will be discussed. The talk will also cover the underlying principles of how these barriers may be
reduced and strategies to ensure that informed decision-making takes place in a way that is consistent with the
values and aims of the people we serve.
SS 1-C
Common Ethical Issues in Genetics and Genomics: A Clinic Based Experience
Stephen Lam (Hong Kong)

Honorary Professor, Faculty of Medicine
Chinese University of Hong Kong
Upon the completion of the Human Genome Project in 2003, the clinical practice of medicine has gone into
a new phase. With the massive data and information that had been generated from individuals and populations, the
clinical applications of modern genomics has exponentially increased in the past decade, and with it, discussions on
existing and novel ethical issues. In the field of reproductive medicine, advances in genetics and genomics has
reactivated debates in issues such as ‘design babies’, which is now made possible by technologies as exemplified by
in vitro fertilization plus preimplantation genetic diagnosis and screening. In other fields of medicine, the debate
centers on how best to utilize these new technologies, such as screening for variants that may have health
implications, and how best to offer diagnosis for diseases with a view to provide for personalized medicine, of which
pharmacogenomics and genetic therapies are subjects for scrutiny. In general, the concerns about personal privacy,
individuals’ confidentiality and genetic discrimination are recurrent themes. These concerns are further fueled by
our increasing capability to interrogate our genome, which raises yet other issues such as the security of data
storage, and ownership of these data. These issues will be discussed in this presentation.
SS 1-D
Establishing a statewide genetic counselors’ association through an iterative process
Linda Steinmark1, Maria Gyure2, Karina Brierley3, Ellen Matloff4, John Neary5, Beverly Tenenholz5, Kara Young6, Kunal
Sanghavi1
1
The Jackson Laboratory for Genomic Medicine
2
University of Connecticut, Storrs
3
Yale Smilow Cancer Genetics and Prevention Program
4
MyGeneCounsel
5
The Hospital of Central Connecticut, Hartford Healthcare
6
PerkinElmer Genomics
10
The field of genetic counseling has significantly evolved since its inception in 1955. The purpose of
developing the Connecticut Genetic Counselors’ Association (CTGCA) through an iterative process is to understand
the needs of genetic counselors in the state and identify collaboration areas. The long-term goal is to sustainably
support the integration of genetic counseling expertise in clinical, research, technological, and educational initiatives
in the state including the ethical, legal, social issues (ELSI) and policy considerations. An Institutional Review Board-
approved online survey was administered to GCs in CT. Four in -person and three virtual focus groups were
conducted to inform the development of CTGCA similar to other states in the United States. Additional discussions
were conducted with leaders of statewide GC associations in three other states. Discussion questions were finalized
by CTGCA planning committee and pilot tested with GCs both inside and outside CT. 34/36 (94%) survey respondents
were interested in a statewide association of GCs in CT. Professional issues, educational leadership needs, and GCs
in bioscience topped respondents’ choices on interest areas. Other areas included innovative service delivery
models, state genetics/genomics plans, and genetic counseling student rotation opportunities. All focus groups
participants (31;100%; 29 GCs, 1 clinical geneticist, 1 genetics fellow) thought that CTGCA should play a central role
in professional development and collaborations for GCs with other healthcare providers. Common interest areas
from the focus groups include developing a statewide resource of genetic services, research collaboration, clinical
referrals, and early introduction of genetic counseling at various levels of education. Participants highlighted ELSI
and policy considerations in all discussion questions. Next steps include a thematic analysis from the focus groups
and strategic logistics execution for CTGCA. This iterative process with a cyclical evaluation component provides an
example of professional development opportunities for GCs to establish a statewide GC association. This model
could be applied in different settings and further foster collaborations.
SS 1-E
Reclassification of Variants of Unknown Significance (VUS): Impact on Clinical Management and Genetic
Counseling
Rifhan Azwani Mazlan

University Malaya Medical Centre
Reclassification of a variant of unknown significance (VUS) is expected in every genetic testing. It is crucial
for medical professionals to explain the reclassification of VUS as one of the genetic test outcomes to clients before
a genetic test is done. Variant reclassifications may change the clinical management of clients; information provided
during genetic counseling may have psychosocial impact on the patients, the clients and their families. We described
a case series of reclassification of variant to understand its impact on clinical management and genetic counseling.
Two patients diagnosed clinically with neurofibromatosis (NF) type 1 and spinal muscular atrophy (SMA),
respectively, were referred to the Genetics Clinic, University Malaya Medical Centre (UMMC) for confirmation of
diagnosis and genetic counselling. The first patient (LJY) was found to have a VUS c.3644T>G (p.Met1215Arg) in the
NF1 gene. Even though this variant has been reported in literature in an individual affected with NF type 1 and a
deletion of this codon (p.Met1215del) has been determined to be pathogenic in multiple individuals affected with
NF type 1, the variant was still classified as VUS due to the insufficient available evidence to determine its role in
disease. This variant was classified as VUS because the methionine residue was moderately conserved and did not
present in population databases. A VUS c.1633A>G (p.Asn545Asp), was identified in the BICD gene in the second
patient (LWC). The variant was also classified as VUS because the available evidence was currently insufficient to
determine its role in disease; the asparagine residue was highly conserved; the variant has not been reported in the
literature in individuals with BICD2-related disease; and was also not present in population databases. Parental tests
were performed in both cases after genetic counseling. Each of the VUS were not identified in LJY’s and LWC’s
parents, respectively, and most likely occurred de novo. By including this new information from family studies, the
VUS identified in LJY was reclassified as Pathogenic and the VUS in LWC was reclassified as Likely Pathogenic. Because
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of the new classification of the variants, adjustments to genetic risk prediction, health surveillance and clinical
management were done and explained to the parents. The parents experienced changes in the level of distress due
to the certainty of the clinical implications of the variants to their children. Parental testing is important to determine
the clinical significance of variants. It is vital that pre-test genetic counselling include an exhaustive discussion on the
possibility of VUS following genetic testing.
Revolutionizing Newborn Screening: New Developments and New Dilemmas
SS 2-A
Genomic Sequencing of Newborns – Are we Ready?
Carmencita D. Padilla (Philippines)

Professor of Pediatrics, University of the Philippines Manila
Institute of Human Genetics, National Institutes of Health Philippines
With the availability of cheap, efficient DNA sequencing technology, there have been predictions on a
dramatic change in the medical landscape spanning diagnosis and treatment. There have been speculations that
genomic sequencing will eventually replace traditional newborn screening and that with the baby’s genome
sequenced, information can used for personalized strategies for disease prevention, diagnosis and management. In
2010, the Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT) program was established to
explore the implications, challenges and opportunities associated with the possible use of genomic sequence
information at the newborn period. Two projects focused on the use of genomic testing in clinical contexts; two
focused on questions that arise when sequencing is used for population screening; and one examined the ethical
and policy issues arising from the application of genomic sequencing in newborns. After a 4-year research process
funded by NIH, an independent review of datasets presented their findings and recommendations. While it is
recognized that there is considerable benefit in using targeted sequencing to screen for or detect specific conditions
that meet the criteria for inclusion in newborn screening panels, use of genome-wide sequencing as a sole screening
tool for newborns is at best premature for the following reasons: 1) many variants are rare or unfamiliar and must
be classified based on very limited data; 2) many variants, including those classified as pathogenic or likely
pathogenic, are in genes that exhibit reduced penetrance, and therefore it is possible that the individual with the
variant will not develop the associated condition or trait; 3) many genes exhibit variable expressivity; 4) databases
used for interpretation of variants are based on data primarily about people of European ancestry, who are
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overrepresented in studies but do not represent the general population; and 5) interpretation of variants is
particularly challenging because, for most babies, very little phenotypic information is available. The session will
briefly discuss the results of the NSIGHT projects and present the summary of Ethics and Policy Advisory Board
recommendations across three contexts: clinical practice, public health, and direct-to-consumer service.
SS 2-B
Newborn Screening Beyond Metabolic Disorders: Successes and Challenges in Introducing New Tests

Director of the New South Wales Newborn Screening Programme
Newborn Screening Programmes worldwide have long considered criteria for inclusion of disorders and take
care when setting action limits to optimise sensitivity, specificity and positive predictive value (PPV). There are many
disorders being watched by program management for changes in the criteria including modification in available tests
or treatment. Population screening of newborns commenced in 1963 with screening for Phenylketonuria (PKU) using
dried blood spot samples. PKU is an autosomal recessive inborn error of metabolism where individuals are unable
to process the proteins in their diet. Screening for conditions other than metabolic disorders has been incorporated
in routine screening programmes since the 1970s with the addition of screening for congenital hypothyroidism. This
was soon followed by screening for haemoglobinopathies and cystic fibrosis. In the 1990s the use of tandem mass
spectrometry allowed the screening of many metabolic disorders with programmes now able to include over 30
disorders on the same sample at the same time. The use of molecular testing was included in newborn population
screening in the 1990s. At first this was as a second tier test on the original sample used to provide additional
information to reduce the number of false positive tests from the primary screen assay, and improve the turnaround
time to diagnosis. For CF, second tier DNA reduced the time to diagnosis and improved the screening protocol from
4% PPV for initial protein testing to 50% if one variant was ascertained and 100% if 2 variants were detected.
Disorders using DNA tests as the primary screen are used when there is no suitable biochemical marker. In the USA
and more recently in Australasia and Europe screening using DNA based assays for immune deficiencies especially
severe combined immunodeficiency (SCID) have been included. SCID can be detected by quantitating the number
of copies of T-cell receptor excision circles detectable in the blood sample. The test measures a fragment of DNA
excised during maturation of T-cells. A number of secondary conditions including prematurity may have a positive
screen. Other disorders where testing DNA is the primary test include Fragile-X and neuromuscular disorders
particularly spinal muscular atrophy (SMA). Tests included in newborn screening determine aspects of the DNA
including the copy number variants of fragments of DNA to indicate the likelihood of symptoms. Importantly the
benefit of early diagnosis and initiation of treatment on outcome is now recognized for SMA, with the most beneficial
response to treatment to date seen in patients treated before the onset of symptoms. For disorders with a brief
presymptomatic window, newborn screening provides the optimal benefit. However, if DNA is a first tier test there
needs to be functional testing as well, as not every person with a parti
SS 2-C
Newborn Screening for LSDs: Current Status and Future Directions

Clinical Professor, Department of Pediatrics
National Taiwan University
Newborn screening (NBS) is recognized as a highly effective public health program to detect certain diseases
before long term health consequences occur. With advances in screening technologies such as the introduction of
tandem mass spectrometric (MS/MS) analysis and available therapeutic options, the number of diseases included in
NBS programs has undergone rapid expansion in recent years. Lysosomal storage disease (LSD), such as infantile-
13
onset Pompe disease and Hurler disease, require earlier recognition so that the disease-modified treatment can
effectively improve the outcomes. Therefore, we introduced the first program to implement Pompe newborn
screening to investigate the benefits of early diagnosis and early treatment with recombinant human acid α-
glucosidase (GAA) in infantile-onset Pompe disease (IOPD). Subsequently, we demonstrated the benefit of early
intervention, and as a result, Pompe disease and Hurler disease have been listed in the recommended universal
screening panel (RUSP) in the United States. Since then, both the screening formats and the screening algorithm
improve a lot. Multiplex is the trend and two forms, using different substrates, are available on the market. Second-
tier testing, using biomarkers, genotyping, or measurements ratio, are developing to increase the positive prediction
rate. However, the timely diagnosis coupling with a timely treatment is the central theme of newborn screening.
The emphasis on the timeliness of newborn-screening, the rapid induction of immune modulation to minimize future
anti-drug antibodies formation, and the availability to the specific treatment are supporting components for a
successful screening program. Furthermore, screening reveals a new era with the modified natural history of the
disease and possible new phenotypes of those current variants of unknown significance. While more researchers
will enhance our understanding of the disease and build up our knowledge, adequate genetic counseling, education
and support for both parents and patients should be encouraged.
SS 2-D
Cystic fibrosis in Asia, an underestimated problem
Gerard Pals1*, Winny Xie1

1
Prodia Clinical Laboratory, Jakarta, Indonesia
(*Corresponding Author: djiu_winny@yahoo.com)
It is generally assumed that Cystic fibrosis (CF) is not found in Asia, or is at least very rare. However, cystic
fibrosis has not been thoroughly investigated in East Asian populations. If it is true that carriers of a pathogenic CF
variant have a better chance of survival during a cholera epidemic, we would expect a carrier frequency similar to
the 1 in 30 or 1 in 25 individuals as found in Europe. The low carrier frequency in Asians is based on a study of Asian
Americans that were tested with the panel of CF variants. That panel, however, is based on variants that have been
found in Europe and in European Americans. Any specific Asian variants in the CF gene, that theoretically may have
a high frequency, were not considered in that study. Next generation sequencing has led recently to creation of large
databases such as the ExAC database, with large numbers of exome sequences, which can be used to assess carrier
frequencies. We checked the ExAC database (Exome Aggregation Consortium), that contains exome sequences of
some 60,000 individuals, including some 9,000 of East Asian descent. We looked for carriers of known pathogenic
variants, and for nonsense and frameshift variants, that are considered to be certainly pathogenic. In the East Asian
individuals we found 32 certainly or likely pathogenic variants in the CFTR gene, with a total carrier frequency of
2.93%, or one in 34 individuals. This is close to the 1 in 30 that is found in Europe. The 2.93% is a low estimate,
because any pathogenic variants that are present in the East Asian population, but not in the European, are not
included. The high frequency of carriers in the East Asian population is not reflected in a high number of known
patients. This is probably due to early death of pneumonia or suspected parasite infection of undiagnosed CF
patients. In Indonesia, with 4.4 million newborns per year, we expect an incidence of CF in newborns of at least 937
CF patients per year, whereas, to our knowledge, no children have been diagnosed with CF. So “underestimated
problem” in the title is actually an understatement. This is probably true for many inherited diseases.
14
SS 2-E
Newborn Screening for Lysosomal Storage Disorders: Comparing Performance of Tandem Mass Spectrometry
and Digital Microfluidics Platforms
Bradford Therrell (USA)

Consultant and Director
National Newborn Screening and Global Resource Center
Newborn screening (NBS) for lysosomal storage disorders (LSDs) has gradually gained momentum over the
past decade. Several LSDs have been nominated for inclusion in the Recommended Uniform Screening Panel (RUSP)
in the U.S. and Pompe Disease (added March 2015) Mucopolysaccharidosis Type I (MPS I) (added February 2016)
are now included as core conditions recommended for inclusion in all state NBS panels. While only Pompe Disease
and MPS I are the only LSDs on the RUSP, some state legislatures have included other LSDs in their state mandated
programs (e.g. MPS II, Fabry, Krabbe) and others are being considered. It is important to review the screening data
when considering the algorithm to be used, including the laboratory screening methodology. The ability of a testing
method to discriminate normal from affected samples must take into account the multiple sources of variability
(biological/genetic variability, DBS sample quality, gestational age at sampling, for example) that exist between
newborn samples. This report seeks to review current data on two screening methodologies being used in U.S.
screening programs. Methodologies and data were examined from programs using one of two LSD laboratory
screening platforms for the RUSP-approved tests - tandem mass spectrometry (MS/MS) and digital microfluidic
fluorometry (DMF). Both platforms have FDA-approved specific reagent kits, use synthetic substrates, and have the
ability to screen for multiple LSDs in a single run. Rich output data sets from the prospective LSD screening programs
in Missouri (DMF) and Illinois (MS/MS) were reviewed. Available data do not show significant differences between
either screening platform in terms of the positive predictive value (PPV). It is clear, however, from these and other
data that additional measures are required to improve the PPV of the screening tests for both MPS-I and Pompe
disease before results are reported. Available data will be presented and discussed. Active and pilot LSD screening
programs in the United States are currently continuing to collect screening data and instrument manufacturers are
working to improve their LSD screening products. Either of the two screening platforms in use appear to give
satisfactory screening results. The emerging clinical results from screening programs in the U.S. and elsewhere
should be continuously analyzed to determine the real world performance of each screening platform in an unbiased
way. Consideration of the appropriate screening platform must include associated costs (equipment, maintenance,
personnel, etc.) and workflow in order to determine most effective LSD screening strategy for the local NBS
laboratory environment.
15
Prenatal Genetics: How Genetic Technologies Are Shaping Reproductive Decision-Making
SS 3-A
Cytogenomic Array and Prenatal Applications: Diagnostic and Counselling Issues
Brian Chung (Hong Kong)

Associate Professor, Paediatrics and Adolescent Medicine and Center for Genomic Sciences
LKS Faculty of Medicine, University of Hong Kong
Cytogenomic array is recommended as a first tier investigation for patients with developmental delay,
intellectual disability, autism spectrum disorder, and multiple congenital anomalies. Many countries have already
endorsed the use of cytogenomic array in place of karyotyping for prenatal diagnosis and it has been commonly
accepted as part of prenatal diagnosis in Hong Kong. We reviewed all cytogenomic array findings in Tsan Yuk
Hospital, a major prenatal diagnostic center in Hong Kong from June 2012 to December 2017. The indications
included abnormal ultrasound findings, positive Down syndrome screening, abnormal non-invasive prenatal test
results, advanced maternal age and family history of chromosomal abnormalities. There were a total of 1261
subjects included in our review and 154 subjects (12.2%) carried at least one pathogenic copy number variants
(CNVs). Pathogenic CNVs were most commonly identified in Chromosomes 16 (n=26), 15 (n=20) and 22 (n=18)
respectively with classical 22q11.2 deletion being the most common microdeletion syndrome. Reporting policy in
prenatal diagnosis varies among laboratories and in different countries. It is ethically distinct from that in postnatal
setting as the couple may decide to terminate their pregnancy even without solid evidence that the fetus/child’s
health and neurodevelopment will be affected. While details of our study has been reported by Cheng S.S.W, Chan
K.Y.K. et al in “Experience of chromosomal microarray applied in prenatal and postnatal settings in Hong Kong” (Am
J Med Genet Part C.2019;1-12), we shall highlight some of the diagnostic and counselling challenges encountered
using case examples from our practice in Hong Kong.
16
SS 3-B
Prenatal Genetic Screening: Current Guidelines and Recommendations
Juliana Lee (Malaysia)

Consultant, Genetic Counsellor
Genetic Counselling Asia
Genetic testing and screening modalities used in pregnancy are offered with the aim of providing patients
information that can help them optimize their pregnancy outcomes. In many countries, the use of maternal serum
marker screening and ultrasound imaging to detect aneuploidies and other birth defects are a routine part of
prenatal care in the first and/or second trimesters. However, both these approaches have a false-positive rate of
approximately 5% and detection rates of 50–95%. In 2011, non-invasive prenatal screening (NIPS) that relies on the
presence of cell-free (cf) DNA derived from the placenta but circulating in maternal blood was introduced as the
most advanced prenatal screening to detect common aneuploidies as early as 10 weeks gestation with lower false
positive rates. However, NIPS remains to be a prenatal screening test despite its higher accuracy due to its limitations
that cannot definitively diagnose or rule out genetic conditions. False positives results may still occur due to many
other factors that influence cfDNA screening performance, therefore it may not be the most appropriate option for
every pregnancy. In 2012, the American College of Medical Genetics and Genomics (ACMG) made a statement on
NIPS as the most effective screening test for aneuploidy in high risk women and is one option that can be used as a
primary screening test in women at increased risk of aneuploidy. NIPS should be an informed patient choice after
pre-test counseling and a patient with a positive test result should be referred for genetic counseling and should be
offered invasive prenatal diagnosis for confirmation of test results. In 2016, ACMG and National Society of Genetic
Counselors (NSGC) updated their statement to support any patient considering NIPS regardless of risk status. Pre-
test counseling for NIPS remain crucial and recommended, however, it needs to go beyond discussions of common
trisomies. The use of NIPS to include sex chromosome aneuploidy screening and screening for selected copy-number
variants (CNVs) is common practice because there are no other screening options to identify these conditions.
Therefore, a review of family history for other forms of screening or prenatal diagnosis is recommended. Prior to
undergoing NIPS, patients should have the opportunity to meet with qualified providers who can facilitate an
individualized discussion of patients’ values and needs, including the option to decline all screening or proceed
directly to diagnostic testing. An increased risk report of NIPS should be confirmed through prenatal diagnosis testing
prior to considerations for termination of pregnancy. Laboratories are encouraged to support the needs of providers
and their patients by delivering meaningful screening reports and to engage in education. Patients with increased
risk results in prenatal screening should have access to genetic counseling through genetic counselors or clinical
geneticists to facilitate informed decision making on diagnostic testing and clinical management of their pregnancy.
SS 3-C
What Not to Expect When You Are Expecting: Causes of Discordant NIPT Results
Kathleen A. Leppig (USA)

Chief, Genetic Services, Kaiser Permanente of Washington, Seattle, WA 98112 USA
Non-invasive prenatal testing (NIPT) has been rapidly embraced as the test of choice by obstetric providers
as it allows the detection of fetal aneuploidy during the first trimester without the risk associated with invasive
procedures, such as chorionic villus sampling or amniocentesis. The test utilizes massively parallel sequencing of
cell-free DNA (cfDNA) present in the plasma derived from a pregnancy women’s peripheral blood sample, which
represents a comingling of both maternal and fetal DNA. With the global widespread adoption of NIPT as a screening
tool, there have situations identified when the NIPT results are discordant from direct fetal karyotyping. Explanation
of this discordance have included confined placental mosaicism, co-twin demise, maternal chromosomal mosaicism,
maternal bone marrow transplant and maternal malignancy. Determining the etiology of discordant NIPT results is
essential to provide accurate risk assessment of a pregnancy and maternal care.
17
SS 3-D
Clinical implementation of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong
Chung CCY, Chan KYK2, Tang MHY2, Chung BHY1, Kan ASY2
1
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
2
Prenatal Diagnostic Laboratory, Tsan Yuk Hospital, Hong Kong
The clinical- and cost-effectiveness of genome-wide array comparative genome hybridization (aCGH) over
karyotyping in invasive prenatal diagnosis has been demonstrated in studies around the world. Yet, in the Hong Kong
(HK) public healthcare setting, aCGH is self-financed while karyotyping is offered free as the standard parental test,
leading to over 58% pregnancies requiring diagnostic procedures to decline aCGH. With the advantage of providing
higher resolution analysis of chromosomal aberrations in a shorter turn-around time using aCGH, we proposed to
use aCGH instead of karyotyping as a primary test, following rapid aneuploidy detection (RAD) to all pregnancies
undergoing invasive diagnostic procedure in HK. The objectives are to evaluate the clinical- and cost-effectiveness
of the proposed algorithm for prenatal diagnosis. The proposed algorithm was performed for 130 prospectively
recruited pregnant women who required invasive prenatal diagnosis between November 2014 and February 2016
at two public hospitals in HK. The clinical-effectiveness focused on the diagnostic rate between the proposed and
current algorithm. Cost data was replicated using non-parametric bootstrapping and the cost-effectiveness was
judged using the incremental cost-effectiveness ratio. Further analysis of incorporating willingness-to-pay (WTP) for
aCGH and the impact of government subsidy were performed. The proposed algorithm with aCGH dominated the
current algorithm in both clinical- and cost-effectiveness. The additional diagnostic rate of aCGH was 10.8% following
RAD, versus 3.9% using karyotyping. The proposed algorithm was significantly cheaper than that of the current
algorithm (-HKD$7768/diagnosis; p<0.05). Fig 1 shows 1000 bootstrapped replicates of incremental diagnostic rate
and incremental costs per sample. Diagnostic rate could improve with governmental subsidy on aCGH.
Implementation of aCGH as a primary test following RAD for invasive prenatal diagnosis maximizes the diagnostic
rate and saves cost. Our results indicated that aCGH could replace majority of karyotyping for prenatal diagnosis in
HK.
SS 3-E
Experiences of Chromosome Analysis Confirmation of NIPT for Numerical Chromosome Abnormality in
Indonesia
Hannie Kartapradja, Nanis S. Marzuki, Chrysantine Paramayuda, Debby D. Ambarwati, Alida R. Harahap
Eijkman Institute for Molecular Biology Jakarta, Indonesia
The objective of this study is to assess the accordance of NIPT and karyotyping results from amniotic fluid
samples. A descriptive analysis study which reviewed karyotyping results of 16 samples referred by clinicians that
was screened using NIPT that came with the referral letter. Conventional cytogenetics analysis was performed on
20-40 metaphases cells of synchronized amniotic fluid samples. GTL-banding technique and the images captured
was performed using VideoTesT-Karyo 3.1 System (VideoTesT, ltd). Interphase FISH of chromosomes 13, 18, 21, X
and Y using Vysis FISH Chromosome Probes (Abbot Molecular) were done for some samples and the images captured
using NIS-Elements 2.30 Software (Nikon). Sixteen samples of the NIPT results were divided into 4 groups: high risk
of chromosome abnormalities on sex chromosome (4), autosomal chromosome (9); low risk (1) and high risk (2) of
unknown chromosome abnormalities. To confirm the NIPT results, 9 samples were karyotyped, 6 samples were
karyotyped and FISH, and 1 sample was done by FISH only. Only 1 of 4 samples diagnosed as sex chromosome
numerical abnormalities by NIPT showed in accordance with karyotyping (47,XXY). The other samples showed
discordance with karyotyping (46,XX). FISH applied to 2 of 3 samples which had NIPT result of 45,X and 47,XXX; the
results showed mosaicism of numerical abnormalities that are in accordance with NIPT at low level (0.3% and 2.3%
18
respectively). Nine samples referred with high risk to have autosomal numerical abnormalities (5 trisomy 21, 2
trisomy 18, 1 chromosome 7 and 10 abnormalities, 1 chromosome 13 and 21 abnormalities). Four of 5 trisomy 21
samples were confirmed by karyotyping had trisomy 21, and the other one had normal karyotype. FISH was done on
one sample and confirmed as a trisomy 21. Of 9 trisomy 18 samples, 1 was confirmed as a trisomy 18 by karyotyping
and FISH, the other one confirmed by FISH only. Two samples with high risk on chromosome 7 and 10, and
chromosome 13 and 21 abnormalities had in accordance with normal karyotype. Two samples with high risk of
unknown chromosomal abnormalities were found to have karyotype of trisomy 21 in one sample and normal
karyotype on another. One sample with low risk was found as a normal karyotype. The above results showed there
is a discrepancy between NIPT and karyotyping results. The discrepancy was found in the low levels of numerical
chromosome mosaicism using FISH. In general, 7 out of 16 samples are discordant between both techniques.
Conventional karyotyping is known as the gold standard test for chromosomal abnormalities especially in Indonesia.
There are discordant between NIPT and karyotyping results. NIPT is only a screening test for high risk chromosomal
abnormalities and not for a definitive conclusion. The result of NIPT needs to be confirmed with other techniques
such as karyotyping and/or FISH.
ACMBMB Hemoglobinopathies: Advances in Diagnosis and Innovative Therapeutics
SS 4-A
Novel Screening for Thalassemia by NGS
Chen Ping (China)

Vice Director, Thalassemia Research Institute and Life Sciences Institute
Guanxi Medical University
Next-generation sequencing (NGS) has been shown to allow rapid, multiplex and high-throughput detection
of genetic variants. A clinical next-generation sequencing test can be designed to target a panel of selected genes,
the exome, or the entire genome. Recently, NGS has been applied for thalassemia screening. PCR-NGS was
performed within dex PCR strategy method for DNA amplification and identification, where each sample was
amplified by designing series of different index primers. Target NGS approach was designed to cover entire globin
genes coding regions, their key regulatory regions and modifier genes such as KLF1, BCL11A, HBS1L and MYB. These
methods have been demonstrated to be a tool for thalassemia carrier screening.
19
SS 4-B
Diagnosis and Classification of non-transfusion dependent thalassemias
Supachai Ekwattanakit (Thailand)

Adult Hematologist, Thalassemia Center
Faculty of Medicine Siriraj Hospital, Mahidol University
Since an introduction of new terminology, non-transfusion dependent thalassemia (NTDT), in 2012 as result of
more clinical data from this group of patients during the last decade, international and several national guidelines
for thalassemia have been updated in order to guide clinicians for the best treatment approach for NTDT patients.
NTDT is classified by clinical judgment on the basis of the regularity of blood transfusion required for survival of
thalassemia patients. This term is dynamic and recommended to be determined by the current transfusion status of
patients, which could be confused for clinicians who are not familiar with its definition and may lead to inappropriate
long-term treatment. Also, there are board clinical spectrum of NTDT patients from those with mild severity (such
as deletional Hb H disease) who do not require any blood transfusion to those with more severe disease form (non-
deletional Hb H disease or moderately severe Hb E/b-thalassemia) that need regular transfusion later on in their life.
Therefore, clinical evaluation in terms of transfusion needs to be regularly performed mainly in patients that
transition from childhood to adolescence or from adulthood to the elderly. Currently, there are no definite predictive
criteria to classify the severity of NTDT patients, except for clinical presentation and globin mutation type itself. Our
recent long-term study in elderly NTDT patients suggested that spleen size is one of the most important markers
that could determine the long-term clinical outcomes, including baseline Hb levels and transfusion requirement.
Lastly, using a genomic approach such as whole genome sequencing (WGS) as a tool for genetics study in thalassemia
makes it possible to simultaneously explore the complexity of numerous genes related to anemia that could play a
role in clinical outcome
SS 4-C
Gene Therapy for Thalassemia: Discoveries in the New Millennium
Suthat Fucharoen, Saovaros Svasti, Alisa Tubsuwan (Thailand)

Institute of Molecular Biosciences, Mahildol University
Thalassemia is one of the most common single gene disorders worldwide. Current treatment, for severe
cases, is regular blood transfusion and iron chelation in cases with iron overload. For many years, the only cure for
thalassemia is stem cell transplantation which is expensive and requires appropriate HLA matches donor. Gene
therapy for thalassemia has been trial in the last few years. Three major approaches include 1) gene addition, e.g.
addition of beta globin gene; 2) gene correction which is mutation specific and 3) reactivation of gamma globin gene.
The 2nd and the 3rd one is still in research and will need some more years before clinical use. The addition of normal
beta globin gene into the stem cell of thalassemia using lentiviral vector and follow by autologous transplantation
has given a good result. The levels of hemoglobin A is increased and reduced transfusion requirements. It is now
being approved to be used in Europe. On top of beta globin gene replacement there is also a trial to reduce excess
amount of alpha globin chain by the regulation of alpha globin gene. These two combinations may give better result
of gene therapy in beta thalassemia. Another alternative approach is antisense therapy. Some beta thalassemia
mutations affect splicing of beta globin mRNA. Antisense oligonucleotides have been developed for the treatment
of beta 654 and IVS I-110 mutation. In this approach antisense oligonucleotide has been applied to modify gene
expression either by down regulation of undesired genes or correction of aberrant splicing. Antisense
oligonucleotide is effective in restoration of correct splicing of mutated beta globin-pre mRNA in vivo, in stably
transfected cell lines, and in vitro cultured progenitor cells of thalassemic patients and in the thalassemic mice
model. Gene-editing technology may be used to genetically modify the endogenous DNA of hematopoietic stem
cells. Specific correction of the genome can be made by nucleases enzyme. Since the cause of beta thalassemia is
20
mostly occurred from a point mutation, thus it is suitable for correction by gene-editing technique. Moreover, this
gene editing may be designed to regulate the transcription factor BCL11A, which suppresses expression of gamma
globin gene. Even gene therapies is benefit to beta thalassemia patient, however, the current technique is still
complicated and expensive. The majority of patients, especially in the developing countries, will have problem to
access to gene therapy.
SS 4-D
Global Globin 2020: Asian Perspective

Senior Consultant Pediatrician and Clinical Geneticist
Hospital Universiti Sains Malaysia
Haemoglobinopathies are among the most common monogenic diseases in Asia, especially in the south
and southeast Asia. In southeast Asia, α-thalassaemia, β-thalassaemia, Haemoglobin (Hb) E and Hb Constant Spring
(CS) are prevalent, and HbE is the most prevalent haemoglobin variant in the southeast Asian region. The Global
Globin 2020 (GG2020) Challenge is a global initiative of the Human Variome Project (HVP), established to apply
developments in human genomics to fight haemoglobinopathies and build capacity for clinical services, genomic
diagnosis and research in its member countries. This presentation will focus on recent developments in Asian
countries, their mutations spectrum and disease management, including the progression on the development of a
new point-of-care rapid diagnostic device for beta thalassemia targeted for screening the southeast Asian
population. This presentation will also discuss about ongoing collaboration between various institutes and
organisations within the Asian countries.
Advances in the Diagnosis and Therapy of Inherited Metabolic Diseases
SS 5-A
Inherited Small Molecule Disorders: Current and Future Therapies
Joy Y. Lee (Australia)

Metabolic Consultant, Department of Metabolic Medicine
The Royal Children’s Hospital, Melbourne, Australia
Small molecule diseases are inherited enzyme deficiencies resulting in the accumulation of toxic
metabolites, particularly in the brain. Standard management of these conditions include drug therapies and dietary
modification. However, there are major problems with compliance to the standard therapies and long-term
outcomes still remain suboptimal with significant morbidity and even mortality. New therapeutic options have
21
emerged through the years and clinical trials are underway for future therapies. In this talk, the therapeutic options
for certain small molecule diseases will be covered through a case-based discussion.
SS 5-B
Treatable Inherited Disorders Revisited
Meow-Keong Thong (Malaysia)

Professor of Paediatrics and Consultant Clinical Geneticist
University of Malaya Medical Centre
Development of pharmacological treatment is a major focus of management for genetic diseases in the past
2 decades. Due to the rarity of many genetic diseases, they are also known as rare diseases (RD). A systematic review
of RD reported the global average defined prevalence was 40 per 100 000 (0.04%). Although each individual RD is
rare, collectively they numbered over 6000 types and this pose considerable medical and financial burden on the
individual patient and his or her extended family. About 80% of RD is genetic in nature and 30% of patients with RD
die before the age of five. Patients with RD face numerous challenges, including arduous “diagnostic odysseys”,
delayed treatment due to late diagnosis, low awareness by members of the public and healthcare professionals,
limited access to genetic services and reduced access to life-saving medicines.RD drugs are referred to as orphan
drugs, and the European Commission has authorized 131 orphan medicines, and designated 1459 products as
orphan medicinal products. The US FDA has designated 4016 products to date, of which 565 have been approved
and 555 have been withdrawn. The cost of drugs for RDs is high due to high cost of development of these drugs and
the relative rarity of these conditions. Only a minority of patients with beta thalassaemia major and lysosomal
storage diseases in the Asia-Pacific region receive an annual budget allocation for their treatment. However, with
the increasing number of types of RD patients and the chronic nature of these RDs, the availability of sufficient
funding for treatment has become an important issue. Since 2016, six gene therapy products are now market-
approved pharmaceuticals by US FDA and EMA: two chimeric antigen receptor T-cell products for B-cell cancers and
four for monogenic disorders: β-thalassemia, RPE65-assocated vision loss, spinal muscular atrophy, and adenosine
deaminase deficiency-associated SCID. There are also more than 800 cell- and gene-therapy programs now in clinical
development. Messenger RNA therapy is emerging as a new class of promising medicine for inherited metabolic
diseases such as methylmalonic acidemia, acute intermittent porphyria, and Fabry disease. Nuclease-mediated gene
therapy using genome editing approaches for therapeutic correction of metabolic liver disorders, namely familial
hypercholesterolemia, hemophilia, ornithine transcarbamylase deficiency, hereditary tyrosinemia type 1, and alpha-
1 antitrypsin deficiency are being investigated. The cost-effectiveness of these drugs in RDs requires the use of
appropriate health financing models for chronic diseases. Hence, the concerns expressed by support groups, patients
and families with regards to treatment allocation for RDs are of urgent public interest. In the past, various methods
were used to fund treatment of RDs, including compassionate use of drugs by the pharmaceutical industry, health
insurance, employer benefits, donations from charities, religious bodies or non-governmental organizations, crowd-
funding or simply out-of-pocket payments which were catastrophic for the individual family. The majority of these
approaches were not sustainable in the medium and long term. Recently, the Asia Pacific Economic Cooperation
(APEC) initiated the “APEC Policy Dialogue on Rare Diseases” in 2018. Some countries such as Singapore (1991),
Japan (1993), Taiwan (Rare Disease and Orphan Act 2000), South Korea (2003) and the Philippines (Rare Disease Act
2016) have enacted legislations recognizing RDs and orphan drugs. These legislations expedite the framework for
early diagnosis, treatment and instituting prevention, screening and control of RDs, provide financial incentives and
health budgets to fund the treatment of all RDs and to ensure no patients with RD are left behind.
22
SS 5-C
Broadening the Phenotypes of Inherited Metabolic Diseases: New Discoveries Through WES

Chair of Genomic Medicine, Department of Pediatrics
University of Melbourne
The traditional approach to the diagnosis of inborn errors of metabolism includes careful clinical
assessment, which then will guide the choice of specific investigations, including where appropriate biochemical,
imaging, histopathological and enzymatic studies. Using this traditional diagnostic paradigm, arriving at a diagnosis
can be a complex process. As genomic sequencing technologies have become more readily available, precise and
timely diagnosis has been further facilitated, and if implemented early in the diagnostic odyssey may obviate the
need for invasive and painful testing. Where the clinical picture is atypical, or where traditional diagnostic test results
are unclear, genomic testing may be helpful, particularly where initial biochemical screening points to a family of
genetic disorders, e.g. where serum transferrin isoform testing shows a type I pattern which may be caused by over
a dozen distinct genetic entities. However, genomic testing is not without its challenges, costs, annotation and
curation aside. Factors contributing to the failure to identify rare disease genes include our imperfect understanding
of the biology, phenotypic and genetic heterogeneity, and blended or expanded phenotypes. Moreover, where
whole exome sequencing is used there are still significant complexities in identification of copy number variants,
chromosomal structural variants and expansion repeats, although bioinformatic resources to tackle these issues are
steadily improving. In addition, using whole exome sequencing it is impossible to identify pathogenic deep intronic
variants, and the mitochondrial genome is not included in most capture kits, both of which are tractable if whole
genome sequencing is the sequencing platform that is employed. In this presentation a brief overview of genomic
sequencing will be presented, and the application of the technology through description of some “real life” cases
will be showcased. These cases will highlight the importance of a multidisciplinary team approach, a strategic
partnership which should include clinicians, diagnostic laboratories, bioinformaticians and researchers with
expertise in functional genomics if we are to realise the promise of genomic sequencing technologies.
SS 5-D
Autologous transplantation with genetically edited stem cells for IEM: Pitfalls and possibilities
Gerard Pals (Netherlands)

Department of Clinical Genetics
VU University Medical Center, Amsterdam
Two developments in stem cell culture and genetic editing have led to high hopes of successful options for
gene therapy. Creating induced pluripotent stem cells (iPSC’s) from a patient, followed by CRISPR-Cas9 editing of the
causative mutation for the disease was theoretical an elegant combination that could lead to gene therapy with
autologous cells. The pitfalls, however, were not trivial, there were more off target effects of the gene editing than
was anticipated and the modified iPSC’s were also potentially dangerous by integration of the genes for alteration
of the differentiation potential. Direct transdifferentiation, differentiation of one cell type into another without
going through the iPSC) stage, is difficult to use in this context, because the cell cultures need to be expanded, which
is difficult with transdifferentiated cells. Non-integrative induction may solve this problem, while the recently
developed Base Editor technique, an improvement of the CRISPR/Cas9 technique, may avoid off target effects of the
genetic editing. Alternatively, for therapeutic purposes, bone marrow stem cells may be collected by plasmapheresis
from blood of the patient or mesenchymal stem cells from adipose tissue obtained by liposuction. Clinical trials are
ongoing. The changed differentiation potential of iPSC’s makes them unsuitable for the functional study of mutations
that affect cell differentiation. Therefore, we have developed direct transdifferentiation protocols to create different
cell types from skin fibroblasts. The transdifferentiated cells can be used for functional studies, drug developing and
patient specific drug testing. The differentiation of fibroblasts to osteoblasts takes 3 weeks. Differentiation to
23
smooth muscle cells takes 8 days. For patient specific analyses this saves the time (and money!) necessary for
creating iPSC’s.
Discerning the Phenotypes of Genetic Disorders Through Next Generation Sequencing
SS 6-A
Whole Genome Sequencing in Severe Intellectual Disability
Christian Gilissen (Netherlands)
Associate Professor, Department of Human Genetics
Radboud University Medical Center
Intellectual disability (ID) and other neurodevelopmental disorders are in part due to de novo mutations
affecting protein-coding genes. In routine diagnostics of patients with ID only 30-40% of patients receive a diagnosis.
This is largely due to the genetic heterogeneity of ID, technological limitations in identifying genetic variation, and
difficulties in interpreting identified genetic variants. We show that with the application of whole genome
sequencing we can achieve higher diagnostic yields than with exome sequencing. In addition, statistical analysis of
large exome cohorts provide a powerful approach to the identification of novel genes thereby further increasing the
diagnostic yield.
SS 6-B
Next Generation Sequencing: Efficient Tool for the Diagnosis of Rare Genetic Syndromes
Lai Poh San (Singapore)
Head, Human Molecular Genetics Laboratory
Department of Paediatrics, Yong Loo Lin School of Medicine
Rare diseases are conditions that affect fewer than 1 in 5,000 to 1 in 1,500 depending on the national
definitions in each country. Although these diseases are individually rare, collectively they place a significant global
healthcare burden with an estimated 350 million people having a rare genetic disorder. Accurate diagnosis is
important to provide effective disease management, genetic counselling and options for carrier or prenatal
screening. It will also allow identification of individuals suitable for molecular treatment or clinical trials for new
drugs. However, identifying the basis of some of these Mendelian diseases by conventional molecular tests can be
challenging due to the disease aetiology. This is especially when the phenotype presentation is complex and there
is a high degree of clinical and genetic heterogeneity. For example, there are more than 500 recognized genetic
causes for congenital developmental delays and intellectual disabilities with most cases arising due to rare and
24
private mutations. In inherited neuromuscular disorders, there are now some 28 genes known to cause limb girdle
muscular dystrophies (LGMDs). The complexity in disease aetiology is thus reflected not only by the existence of
numerous different genes causing similar disease entities but also by the observation that the same gene mutations
can lead to different clinical and pathological phenotypes. Often, the possibilities for differential diagnosis is too
numerous for targeted gene screening, and linkage analysis is often not possible due to small pedigree sizes and
sporadic cases. The emergence of next gen sequencing (NGS) has led to molecular diagnosis of many unresolved
genetic syndromes in families who had to endure prolonged diagnostic odysseys involving extensive and costly lab
investigations. With decreasing costs and increasing diagnostic yields, NGS is increasingly being deployed in clinical
labs. This talk discusses on the utility of implementing NGS and its challenges and limitations.
SS 6-C
Targeted Sequencing for Skeletal Dysplasia: Paving the Way for Gene Discoveries
David Sillence (Australia)
Emeritus Professor, Genomic Medicine
University of Sydney
Drs Kazimierz Kozlowski and David Sillence held a weekly teaching and consultation session conference
dedicated to Genetic Skeletal Radiology at the Royal Alexandra Hospital for Children (aka the Children’s Hospital).
Over this period the Sillence-Kozlowski Radiology collection accumulated more than 3200 consultation cases. We
noted that for some 50% of the cases we provided a descriptive diagnosis for were unclassifiable in terms of the
International databases available at the time. The discovery of biochemical or genomic correlations was painfully
slow. The first attempt at tabulation of a phenomic and genomic correlation was published in 1992. This molecular
nosology was a huge leap forward in classifying approximately 160 disorders in 26 postulated pathogenetic families.
The International nosology committee has since met every fourth year. The 2019 report included 455 genetic
skeletal disorders from 42 groups. The genomic basis was known for all but 37 disorders. The report of the 2019
Nosology is still in press. The application of techniques of Next Generation Sequencing has not only advanced the
genotype-phenotype correlation of known skeletal dysplasias but is gradually solving the genomics of those puzzling
disorders which we had previously struggled to classify. Both the full clinical delineation of the syndrome of
Microcephalic Osteodysplastic Primordial Dwarfism type I (Taybi-Linder syndrome) and the discovery that this
resulted from homozygous mutations in the non-translated microRNA RNU4atac brought home the realization that
Roifman syndrome and Lowry-Wood syndrome both skeletal syndromes with milder immunodeficiency, growth
deficiency of prenatal onset and learning difficulties were all part of a phenotypic spectrum of disorders resulting
from disruption of the minor spliceosome. We have known for 20 years that at least one skeletal dysplasia, Cartilage-
Hair Hypoplasia (Metaphyseal Dysplasia of the McKusick type) resulted from compound heterozygous mutations in
RMRP, a transcribed but not translated RNA which was the RNA component of the Mitochondrial RNA-Processing
Ribonuclease. In a brilliant collaboration Giedre Grigelioniene and colleagues demonstrated in 2019 that an
extremely rare skeletal dysplasia in humans, Spondyloepiphyseal Dysplasia Nishimura type, resulted from
heterozygous mutations in miR-140 (micro-RNA-140. This microRNA encodes a chondrocyte super-enhancer in
humans and mice. It is likely that further skeletal dysplasia syndromes will be discovered to have mutations in
intronic (non-coding) sequences, most likely detected with WGS. On the other hand WES and WGS have vastly
expanded perspectives in other skeletal disorders such as Osteogenesis Imperfecta. Osteogenesis Imperfecta with
Doughnut lesions in the skull is a rare historic type of OI. This was recently delineated by Outi Makitie and colleagues
to result from mutations in Sphingomyelin Synthase type 2 (SMS2) linking up bone metabolism to the sphingomyelin
metabolic pathway and other potential disorders resulting in Brittle Bones. Genomic studies of Osteogenesis
Imperfecta in different populations reveal marked differences in aetiologic prevalence with studies in Southern
Africa suggesting that autosomal recessive types of OI were more common than dominantly inherited OI resulting
from heterozygous mutations in type I collagen genes. The discovery of SMS2 mutations brings the number of known
genes resulting in monogenic brittle bone phenotypes to 25.
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SS 6-D
Pre and Postanalytical Challenges of NGS: Time for Solutions
Felicitas Lacbawan (USA)
Vice President and Executive Medical Director, Advanced Diagnostics – Genetics, Genomics, R&D and
Bioinformatics
Quest Diagnostics
Timely confirmation of clinical diagnosis shortens the ‘diagnostic odyssey’ as well as facilitate definitive
clinical management and proper genetic counseling. The advancement and improvement of new sequencing
technology, next-generation sequencing (NGS), has recently propelled genetic laboratory diagnosis. However,
challenges in the clinical utilization of genetic tests in precision medicine remains. Some of the challenges of NGS,
both preanalytical and postanalytical, will be discussed together with ongoing solutions that may appropriately
address them.
Population Genetics: Genetic Migration in Asia: From Patterns to Predictions
SS 7-A
Patterns of Genetic Admixture across the Indonesian Archipelago
Herawati Sudoyo (Indonesia)
Principal Investigator, Senior Research Fellow
Eijkman Institute for Molecular Biology
Indonesian archipelago is a crossroad for modern human dispersal out of Africa, reaching as far as Australia
and the Pacific. It is home to a very diverse ethnics, linguistic, and genetic diversity that attracted various studies for
understanding human migration history in this region. Previous study showed that genetic ancestry is strongly
correlated with linguistic affiliations as well as geography. The Indonesian Human Genome Diversity Project,
covering diverse ethnic populations designed to lay the foundation for our understanding of the genetic basis of
disease in Indonesia and to characterize the Indonesian genome variation. The Papuan have the highest genomic
archaic Denisovan introgressed about 5%. It is also revealed that other human populations in ISEA and East Asia
share lower amounts of genetic affinity with Denisovans, suggesting that the archaic introgression event may have
taken place in SEA. A more in-depth study into the introgression will be carried out to the event of modern human
dispersal Out of Africa on the human migration and adaptation and selection related to colonization of Papua (Sahul
land). Another effort to characterize genetic variation across Asian populations through Genome Asia has been
26
started with the ultimate goal of providing a rich resource for precision medicine and molecular diagnostics. The
data allowed generation of pharmacogenomic predictions, identified Asian specific or enriched disease alleles and
demonstrated the value of using Asian allele frequency filters in disease gene discovery. The preliminary dataset
provides resources that will greatly increase the ability to carry out genetic studies in Asian populations and provides
a reference point for scaling efforts towards a much larger catalogue of Asian genetic variation.
SS 7-B
A Filipino Genomes Research Program: Representing the Underrepresented in Genomics Research
Frederick C. Delfin (Philippines)
Program Leader, Filipino Genomes Research Program
DNA Laboratory NSRI – UP Diliman
Studies of different types of DNA (Y-chromosome, mitochondrial, and autosomal) samples contributed by
about 1,000 Filipino participants from 12 regional centers (RC) and 19 ethnolinguistic (EL) groups revealed several
facets of the Filipino population. Filipino groups have genetic affinities with different groups in the Asia-Pacific
region. The DNA of Filipino groups contain genetic signals of ancient demographic events relating to an ancient
genetic history of about 5,000–50,000 years ago. The Filipino population has a complex population genetic structure
composed of genetically close RC groups and genetically distant EL groups. This genetic overview has implications
for the study of human history, forensics, and medicine in the Philippines. However, there is disparity in human
genomics research across the global scientific community. This is because majority of human genomics research
involve or represent individuals with European ancestry. As such, the health care benefits of genomics will only be
applicable to the well represented populations. This situation can worsen existing health care disparities. The
inclusion of underrepresented populations or populations of different and diverse ancestry can address the existing
and continuing disparity in human genomics research. Moreover, accounting for population genetic history
(evolutionary, prehistoric, historic and demographic) can make the output of genomics research transferable to
included populations. To address this disparity for the Filipino population, a Filipino Genomes Research Program
(FGRP) aims to represent and involve (in phases) the various Filipino RC and EL groups and other Filipinos with
relevant demographics (e.g. child sexual assault victims) in human genomics research so that the focus, output,
applications and benefits of genomics research are relevant, transferable and applicable to the Filipino population.
The FGRP currently has three component projects. Project 1: Filipino Forensic Genomics (Phase I) will generate a
Filipino-specific DNA sample resource and population reference database for forensic applications. Project 2: Filipino
Genomes: History, Evolution, Origins and Applications (Phase I): will generate a DNA sample and whole genome data
resource for various applications from basic human genetics to health research. Project 3: Filipino Genome Regions
to Help Resolve Child Sexual Abuse Cases will validate the use of Massively Parallel Sequencing (MPS) technologies
in analyzing sexual assault evidence. Focused and long term relations between researchers and stakeholders through
an iterative and dynamic process, will make the FGRP and its component projects a venue for research work, training,
cooperation, partnerships and appreciation of relevant genetics/genomics concepts, research-ethics and the
research process. As such, the FGRP will be instrumental in the increase of the scientific work force, the expansion
of research partnerships, capabilities and the appreciation for human genomics research across the country. There
is a saying that: “If you are going to work with indigenous communities on genetics, you have to be willing to make
lifelong relations.” It is in this spirit that the FGRP will engage and involve different Filipino groups in Filipino
genomics research.
SS 7-C
Population Genetic structure in Malaysian Sub-ethnic Groups
Senior Consultant Pediatrician and Clinical Geneticist
Hospital Universiti Sains Malaysia
27
Modern human started to migrate out of Africa approximately 140,000 years ago. They travelled along
southern coast of Arabian peninsula towards India and southeast Asia including the Malay peninsula. At present day,
Malaysia has a population of 32.6 million and land borders with Thailand, Indonesia, Brunei and maritime borders
with Singapore, Vietnam and the Philippines. There are three major ethnic groups (Malay, Chinese and Indian); and
an aboriginal group (Orang Asli which consist of Proto Malays, Negrito and Senoi). Genetic studies have shown that
Malaysia’s Orang Asli can be traced back to India and Africa somewhere between 42,000 to 63,000 years ago. After
settling in the Malay peninsula, they adapted to the jungle where they lived almost undisturbed for thousands of
years. This makes the Orang Asli, or ‘original people’, Malaysia’s oldest inhabitants. Malays speak the Malayo-
Polynesian language, a member of the Austronesian language family, and are known to be part of the east Asian
group of races. Malay can be found across southeast Asia, particularly Malaysia, Singapore, Brunei, Indonesia,
southern Thailand, southern Philippines, the Christmas and Cocos Islands of Australian, the western part of Australia,
and up to Sri Lanka and Cape Town of South Africa. This country report on Malaysia will demonstrate that the genetic
heterogeneity of Malay sub-ethnic groups is consistent with their diverse origin and histories and shared genetic
ancestry with mainly Indonesian, Chinese Yunnan and Indian groups. With the slogan “Malaysia, truly Asia”, Malaysia
is a place where different ethnic, religion, culture from various places come together.
SS 7-D
Population Genetics in China in the Context of Precision Medicine
Xu Shuhua (China)
Professor, Human Population Genetics
CAS-MPG Institute for Computational Biology
The genetic background of an individual is a crucial factor to be considered toward personalized medicine
or PM. It is now very feasible to re-sequence an individual genome due to recent advances in DNA sequencing
technologies (in particular, NGS). However, identifying and prioritizing disease-associated causal variants relies on
understanding the distribution of genetic variation within and between populations. In this context, population
genetics and genomics play a vital role in dissecting genetic architecture of complex traits/diseases by separating
locus-specific effects from genome-wide effects. Nonetheless, considering very heterogeneous ethnic groups and
large population size in China, great efforts are necessary to provide a more precise and comprehensive
characterization of the genomic diversity of natural populations. Here, I will give a brief overview of the recent
progresses in human population genetics studies in China, including the fine-scale genetic structure of the Han
Chinese population, the largest ethnic group in the world, and that of some minority groups such as the Tibetan and
the Uyghurs in western China.
ACMBMB Hemoglobinopathies
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SS 8-A
Stem Cell-based Therapies in Thalassemias
Hai Yang Law (Singapore)
Deputy Director, National Thalassemia Registry
Chief Scientific Officer and Laboratory Director, DNA Diagnostic and Research Lab, KK Women’s and Children’s
Hospital
Stem cell transplant has been the only effective cure for Thalassaemia major patients in the last more than
30 years. The source of stem cells has been widen from using fully HLA matched donor from close relatives to using
haploidentical stem cell grafts from related or unrelated donors, and unmatched donor or umbilical cord blood. The
success of engraftment largely depends on overcoming graft rejection and graft-vs-host disease, and close
monitoring and management of post-transplant follow up. Better understanding of immune system is of pivotal
important in improving preparation of T cell depleted stem cell graft. Fine tuning of protocols in stem cell graft
preparation has greatly improved acceptance of graft. The conditioning regime to prepare patients also plays an
important role in reaching a promising clinical outcome.
SS 8-B
Point of Care Testing for Hemoglobinopathies with focus on Thalassemias
Carolyn Hoppe (USA)
Medical Director
Global Blood Therapeutics
Sickle cell disease and thalassemia represent a significant global health care burden in low resource areas
where access to diagnostic testing is limited. Point-of-care (POC) testing for the detection of hemoglobin disorders
are emerging as a practical approach to improve diagnostic capacity in resource-limited countries where the burden
of the disease is greatest. Rapid, inexpensive, easy to use diagnostic assays have been developed for detection of
sickle cell disease and are now being developed for thalassemia. Several POC assays, including two immunoassay-
based POC test kits that show high sensitivity and specificity for detecting SCD have been validated for use in in
newborns and adults. A portable microchip electrophoresis assay capable of detecting and quantifying relative
percentages of normal and variant hemoglobins is being evaluated in field studies. POC tests for the identification
of thalassemia, including an immunoassay for detection of Hb Barts to screen for alpha thalassemia, are in
development. This presentation will review the rationale and the criteria for acceptable POC assay, and discuss the
POC devices currently available and in development for the detection of hemoglobinopathies.
SS 8-C
Vienna Stripassays as an efficient tool for the detection of α and β Thalassaemia mutations
Roch RS1, Yoon CS2, Tan GP2, Tan YM2, Law HY3, Lai AHM3, Tan ES3
1
DNA Diagnostics & Research Laboratory, 2National Thalassaemia Registry, 3Genetics Service,
KK Women’s and Children’s Hospital
Affecting 4% of the population, Thalassaemia is known to be the most common genetic disorder in
Singapore. This condition is caused by the absence or reduced synthesis of the alpha (α) and beta (β) globin chains.
α-thalassaemia is predominantly caused by deletional mutations whereas β-thalassaemia is mainly caused by point
mutations. In this study, we look at the efficiency of a commercial Stripassay kit by ViennaLab Diagnostics, in
detecting the common deletions and mutations that cause α and β thalassaemia in a diagnostic lab. Three different
kits, namely the β - Globin Stripassay SEA (VBSEA), β - Globin Stripassay IME (VBIME) and the α - Globin Stripassay
29
(VA) are used for this purpose. Data for this study has been collated from a period of 3 and a half years (January
2016 till June 2019). A total of 2119 stripassays have been used (VBSEA – 1497, VBIME – 55 and VA - 567) for
screening to confirm thalassaemia status. Out of which, the results were positive for 1250 (83.5%) for VBSEA; 37
(67.3%) for VBIME; 253 (44.6%) for VA. A fraction of the samples with elevated HbA2 values (109), HbH inclusion
bodies or low Mean Corpuscular Values (MCV) values, and with negative results were subjected to sequencing and
PCR for Thai and Fil deletional mutations for β-thalassaemia and anti 4.2kb α-globin gene triplication for α-
thalassaemia. Mutations were identified in 88 out of 109 samples (80.7%) with raised A2 for VBSEA; 8 out of 9
samples (88.9%) with raised A2 for VBIME; and 5 out of 27 samples (18.5%) with low MCV for VA. The actual pick up
rate with the kits are 93.4% (VBSEA), 82.2% (VBIME) and 98.1% (VA). In summary, the Vienna Stripassay kits are quite
efficient in detecting thalassaemia in our local population. However, there are limitations. The large number of β
thalassaemia mutations present in the gene makes it difficult to detect them all in 1 assay. Ethnicity is important for
determining which β kit should be used. Follow-up tests like Sanger sequencing and gap PCR should be considered
for highly suspected cases. As for the α thalassaemia requests, the pickup rate although being small, could actually
be true negatives. This is in view of the fact that the patient may have similar clinical indications that are not only
caused by thalassaemia.
SS 8-D
Alpha and Beta Globin Gene Cluster Haplotypes of Thalassemia Patients in Indonesia –
Are they useful for population biomarkers?
Ita Margaretha Nainggolana,b, Sintia Puspitasaria, Elisabeth Lovian Uli Basac, Giovani E. Alfonsus, Wangd
a
The Eijkman Institute for Molecular Biology, Ministry for Research, Technology and Higher Education, Jakarta 10430,
Indonesia.
b
Department of Clinical Pathology, Faculty of Medicine, Atma Jaya Catholic University of Indonesia, Jakarta 14440,
Indonesia.
c
Program of Biology, Graduate Program, Faculty of Mathematics and Natural Sciences, University of Indonesia,
Depok 16424, Indonesia.
d
Program of Biology, Faculty of Life Sciences, Surya University, Tangerang, Banten 15143, Indonesia
Thalassemia is a group of blood disorders caused by hemoglobin production abnormalities. Alpha ()
thalassemia and beta () thalassemia are the most common types of thalassemia worldwide. There are many
polymorphic sites in  and  globin gene clusters that may useful as a biomarker for specific mutant alleles in
population. The  thalassemia is most commonly generated by deletion of one or both  globin gene, however the
nondeletion mutations are not uncommon. The  thalassemia very often caused by single nucleotide base
substitution and less frequent by nondeletion defects. Both of  and  globin gene cluster haplotypes are
determined by eight polymorphic sites. The aim of this study is to know whether  and  haplotypes can be used as
population biomarker in Indonesian population or no. Eight polymorphic sites in  globin gene cluster including HincII
5’-, HindIII-G, HindIII-A, HincII-, HincII 3’-, HinfI, AvaII, and BamHI were used to define  globin gene cluster
haplotype. The  globin gene cluster haplotype were obtained from XbaI, SacI, IZ/BglI, PZ/Z, AccI, RsaI, αPstI, and
θ.PstI polymorphic sites in  globin gene cluster. The polymorphic sites were examined by polymerase chain reaction
(PCR) based method and followed by restriction fragment length polymorphism (RFLP). Specific mutant allele was
associated with several  globin gene cluster haplotypes. However, there was specific haplotype that sharing among
several  thalassemia mutant alleles. Similar outcome was found with  globin gene cluster haplotypes in 
thalassemia mutant alleles. We analyzed the distribution of specific haplotype in  thalassemia mutant alleles
according to their ethnicity background. Therefore we can map the haplotype distribution in several ethnics of
Indonesian population according to their  and  thalassemia mutant alleles respectively. Certain  and  mutant
alleles were associated with specific  and  globin gene cluster haplotypes. However further study with more
samples is still needed to be able get significant results. This result suggest that this approach can be useful to map
haplotypes as population biomarker in Indonesian population.
30
SS 8-E
Diagnostic yield for further investigation of cases with presence of HbH Inclusion Bodies but negative for routine
alpha thalassaemia mutation screen
Low MHW1, Tan YM2, Tan GP1, Law HY3
1
DNA Diagnostic and Research Lab 2 National Thalassaemia Registry, 3 Genetics Service, KK Women’s and Children’s
Hospital, Singapore
Presence of HbH inclusion bodies in patients with microcytic and hypochromic anaemia usually suggests α-
thalassaemia. DNA screening for common α-thalassaemia mutations will confirm the diagnosis in majority (70%) of
the cases. As presence of HbH inclusion bodies can also be seen in normocytic patients with Hb New York trait – a
β-globin chain variant. This raises the question how many of these patients are true α-thalassaemia carriers. Two
hundred and eleven cases screened in National Thalassaemia Registry from 2016 to 2018 were selected for the
study. HbH inclusion bodies were detected in these samples but routine screening was negative for mutations that
account for 99% of α-thalassaemia (5 types of deletional mutations – Southeast-Asian, Thai, Filipino, 3.7kb, 4.2kb
and 5 point mutations in α2-globin gene – Hb Constant Spring, Hb Quong Sze, Start codon(-T), Cd30(-GAG),
Cd59(GGC>GAC)). These samples were subjected to 1) Hb New York screening, 2) sequencing of both α1 and α2
globin genes to detect rare α-thalassaemia mutations. Hb New York was confirmed in 9.5% of cases (MCV 80.2–95.5;
mean=87.7) and 10.4% had α-globin gene mutations (MCV 61.4–80.8; mean=72). These include 7 α-thalassaemia
causing mutations, 3 α-globin variants and 11 polymorphisms Also, 1.4% of the cases (MCV 73.5–89.8; mean=82.1)
had both Hb New York and α-globin gene mutations. Further investigation on HbH positive cases with negative α-
thalassaemia DNA screening had a diagnostic yield of 21.3%. This high detection rate strongly suggests the need to
incorporate further investigation in diagnostic workflow.
Day 2 Schedule
7:30AM-8:30AM iGNiTE Sessions: Genomic Networking and Training with the Experts (Undiagnosed
Interesting Cases)
Rizal Ballroom A
Brian Chung (Hong Kong) & Eva Maria Cutiongco-de la Paz (Philippines)
SIMULTANEOUS SYMPOSIA (SS)
8:30AM-10:00AM SS 9: Elucidating the Genetics of Complex Diseases: Where Are We Now?
(Rizal Ballroom A)
Chair: Joy Lee
Moderator: Leniza de Castro-Hamoy
8:30AM-8:50AM A: Genetic Testing for Companion Diagnostic Applications in Cancer
Benjamin Roa (USA)
8:50AM-9:10AM B: Integrating Multi-Omics Data for Diabetes Mellitus: Outcomes and Challenges
Mark Seielstad (USA)
C: The Promise of Precision Medicine: Molecular Profiling of Neuroendocrine Tumors and
9:10AM- 9:30AM Its Clinical Potential
Thanyachai Sura (Thailand)
D: Modeling the Aging Process Using Tissue Chips In Space
9:30AM-9:50AM Danilo A. Tagle (USA)
OPEN FORUM
9:50AM-10:00AM
8:30AM-10:00AM SS 10: Understanding Future Trends of Metagenomics, Proteomics and Metabolomics
(Rizal Ballroom B)
Chair: Charles Lee
Moderator: Barbra Charina Cavan
31
8:30AM-8:50AM A: Diagnostic Metagenomics: Applications in the Diagnosis of Dengue Infection
Martin Hibberd (UK)
B: Asian Microbiome Project: Strains, Functions and Dynamics
8:50AM-9:10AM Leslie Michelle Dalmacio (Philippines)
C: miRNAs-C19M regulate the proliferation, invasion and migration in SKBR3 cell lines
9:10AM- 9:20AM Andres Felipe Aristizabal Pachon (Colombia)
D: SINEUPs: a new antisense, long non-coding RNA-based platform to increase endogenous
protein levels for therapy
9:20AM-9:30AM Stefano Gustincich (Italy)
E: Preliminary Investigation on the Role of Canonical and Novel, Non-hotspot KRAS
Mutation in Metabolic Reprogramming
9:30AM-9:40AM Joelle Noriko Galang (Philippines)
OPEN FORUM
9:40AM-10:00AM
8:30AM-10:00AM SS 11: Solving the Brain Enigma: The Value of Genomics in Neuropsychiatric Disorders
(Rizal Ballroom C)
Chair: Stephen Lam
Moderator: Mary Anne Chiong
8:30AM-8:50AM A: What can peripheral gene expression tell us about autism spectrum disorders (ASD)?
Richard P. Ebstein (Israel)
B: Solving the Mystery of the Genetic Cause of X-Linked Dystonia-Parkinsonism: An
8:50AM-9:10AM Integrative Genomics for Rare Neurologic Diseases
Aloysius Domingo (USA)
C: Regulation of neurofibromin 2 by microRNAs: roles in nervous system tumors and other
9:10AM- 9:30AM malignancies
Reynaldo Garcia (Philippines)
D: Brain-on-a-Chip: Human Induced Pluripotent Stem Cells (hIPSCs) as An Ex-vivo Tool for
9:30AM-9:50AM Genetic Classification and Personalized Medicine
Hans van Bokhoven (Netherlands)
OPEN FORUM
9:50AM-10:00AM
8:30AM-10:00AM SS 12: Disorders of Sexual Development: Integrating Clinical and Genetic Approaches
(Pasay AB)
Chair: Mercy Laurino
Moderator: Sylvia Estrada
8:30AM-8:50AM A: Evaluation of Disorders of Sexual Development: Existing Practices and Novel Gene
Breakthroughs
Dung Vu Chi (Vietnam)
8:50AM-9:10AM B: Differences of Sex Development (DSD): Pivotal Roles of Laboratory Genomics
in Diagnosis, Management, Medical Education, and Research
Ina Amarillo (USA)
9:10AM- 9:30AM C: Gender Assignment and Counseling for Disorders of Sexual Development
Sultana Faradz (Indonesia)
9:30AM-9:40AM D: Hormonal and Genotypic Profiles of Individuals Carrying Mutations at SRD5A2 Gene
Nanis S. Marzuki (Indonesia)
E: AR gene mutation analysis of undervirilized 46, XY males in Indonesian population
9:40AM-9:50AM Nurin Aisyiyah Listyasari (Indonesia)
OPEN FORUM
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9:50AM-10:00AM
10:00AM-10:30AM COFFEE BREAK
VISIT TO EXHIBITS
10:30AM-12:00PM SS 13: Improving the Landscape of LSD Care through diagnosis and therapeutics (Genzyme
sponsored symposium)
(Rizal Ballroom A)
Chair: Mary Anne Chiong
Moderator: April Grace Dion-Berboso
10:30AM-10:40AM A: Taiwan Experience of a Nationwide NBS Program for Gaucher Disease
10:40AM-10:50AM B: How to Improve Gaucher Disease Diagnosis: Signs and Symptoms
10:50AM-11:10AM C: Diagnosis and Treatment of Gaucher Disease
Damayanti Rusli Sjarif (Indonesia)
11:10AM -11:30AM D: How to Improve MPS 1 Diagnosis
Ratna Puri (India)
11:30AM -11:50AM E: Screening and Treatment of MPS in Vietnam
11:50AM -12:00PM OPEN FORUM
10:30AM-12:00PM SS 14: OMICS Technologies for optimized and personalized medicine
(PCHRD-Sponsored Symposium)
(Rizal Ballroom B)
Chair: Barbra Cavan
Moderator: Maria Melanie Liberty Alcausin
10:30AM-10:50AM A: Leptospirosis: mechanistic insights and potential molecular prognosticators
Jose B. Nevado Jr. (Philippines)
B: Genetic Susceptibility to SLE Among Filipinos
10:50AM-11:10AM Michael L. Tee (Philippines)
C: Genetic Susceptibility to Cardiovascular Disease Among Filipinos
11:10AM -11:30AM Eva Maria Cutiongco-de la Paz (Philippines)
D: Vitamin D Receptor Mutations and Fragility Fractures
11:30AM -11:50AM Cynthia P. Saloma (Philippines)
OPEN FORUM
11:50AM -12:00PM
10:30AM-12:00PM SS 15: Illumina Genomics Session
(Rizal Ballroom C)
Chair: Mark Seielstad
Moderator: Conchita Abarquez
10:30AM-10:50AM A: Looking for disease genetic markers among epigenetic profiles
George Anene-Nzelu
10:50AM-11:10AM B: Polygenic risk scores and complex disease
Peter Coleman
11:10AM -11:30AM C: Polygenic risk scores and breast cancer
Jingmei Li
11:30AM -11:50AM D: Accurate and Accelerated analysis solutions for Illumina NGS data
Yue Ying Tan
11:50AM -12:00PM OPEN FORUM
10:30AM-12:00PM SS 16: The Emerging Role of Enhancers in Gene Regulation (RIKEN Sponsored Symposium)
33
(Pasay A)
Chair: Catherine Lynn Silao
Moderator: Monette Faner
A: Overview of the Enhancerome Discovered in the FANTOM
10:30AM-10:45AM
Yoshihide Hayashizaki
B: Novel NET-CAGE Technology Reveals the Dynamics and Topology of Human Cis-
10:45AM-11:30AM
Regulatory Elements
Yasuhiro Murakawa
C: Variation and Evolution of Shh Enhancers
11:30AM -12:00PM
Toshihiko Shiroishi
10:30AM-12:00PM SS 17: Inventing the future: MD-PhDs' researches on spotlight (PCHRD sponsored
symposium)
(Pasay B)
Moderator: Leslie Michelle Dalmacio
10:30AM-10:40AM A: Identification of circulating Leptospira among humans and animals in Cabanatuan, Iloilo,
Philippines
Pia Regina Fatima C. Zamora
10:40AM-10:50AM B: Characterization of Epithelial Ovarian Cancer Patients in a Philippine Tertiary Hospital
Ryan Christian V. Lintao
C: Circulating MicroRNAs as Biomarkers for Hepatic Fibrosis Progression in Schistosomiasis
10:50AM -11:00AM Ian Kim B. Tabios
D: Metagenomic Profiling of Gut Microbiome Among the Risk Groups of Atherosclerotic
Coronary Artery Disease
11:00AM-11:10AM Mark Joseph M. Abaca
E: Gene expression analyses of CIDEC and S100A4 in Metastatic Human Papillary Thyroid
Carcinoma
11:10AM -11:20AM Charles Patrick D. Uy
F: Identification of Alpha Globin Gene Mutations in Filipino Newborns Diagnosed with
Alpha Thalassemia
11:20AM-11:30AM Mark John Girasol
G: Role of Hypoxia-induced Factor 1A (HIF1A) on Intermittent Hypoxia-induced Adipose
Tissue Dysfunction in Type 2 Diabetes Mellitus
11:30AM-11:40AM Josept Mari Poblete
OPEN FORUM
11:40AM -12:00PM
12:30PM-1:30PM LUNCHEON SYMPOSIUM INDUSTRY SPONSORED : GENZYME
(Rizal Ballroom ABC)
Common and Uncommon Symptoms , Diagnosis and Management Challenges in Pompe

Disease
Dr. Ratna Puri (India)
Revisiting Current Consensus on the Diagnosis and Treatment of Pompe Disease

Dr. Kanya Suphapeetiporn (Thailand)
GLOBAL PERSPECTIVES IN GENOMICS AND MEDICINE: AN APSHG-HUGO PLENARY SESSION
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Chair: Eva Maria Cutiongco-de la Paz
2:30PM-3:00PM Precision Medicine: Making Sense of DNA Variants

Charles Lee (South Korea)
3:00PM-3:30PM Oncogenomics: Closing the Cancer Gap

Edison Liu ( Singapore)
3:30PM-4:15PM PLENARY SESSION 4
Chair: Thanyachai Sura
Rare Are Common: How Rare Diseases Reveal Molecular Pathways for Common Disorders
Bruno Reversade (Singapore)
4:15PM-5:00PM PLENARY SESSION 5
Chair: Sultana Faradz
Precision Public Health for Infectious Diseases in Asia

Martin Hibberd (UK)
BEST POSTER PRESENTATIONS
5:00PM-7:00PM
COFFEE BREAK AND VISIT TO EXHIBITS
FELLOWSHIP NIGHT
7:00PM-9:00PM
Elucidating the Genetics of Complex Diseases: Where Are We Now?
SS 9-A
Genetic Testing for Companion Diagnostic Applications in Cancer
Benjamin Roa (USA)
Senior Vice President for Technology Development and Senior Laboratory Director
35
Myriad Genetic Laboratories
Increased knowledge of the molecular mechanisms underlying cancer has facilitated the development of
therapies that target specific biomarkers. Development and regulatory approval of certain cancer drugs have been
coupled with companion diagnostics to identify patients who are more likely to derive therapeutic benefit based on
their molecular profiles. A notable example is the poly-ADP-ribose polymerase (PARP) inhibitor class of drugs for
ovarian and breast cancer. These compounds inhibit the PARP enzyme from repairing DNA single-strand breaks that
become converted to double-strand breaks upon DNA replication. The BRCA1 and BRCA2 tumor suppressor genes
mediate the repair of DNA double-strand breaks through the homologous recombination pathway. In addition to
conferring risk for hereditary breast and ovarian cancer syndrome, BRCA1 and BRCA2 mutations constitute a
therapeutic target. PARP inhibition leads to chromosomal instability, cell cycle arrest and synthetic lethality of tumor
cells with BRCA1 and BRCA2 dysfunction and homologous recombination deficiency. The PARP inhibitor Lynparza®
(olaparib) was approved by the US Food and Drug Administration in 2014 as a first-in-class drug for the treatment of
patients with germline BRCA1 or BRCA2-mutated advanced ovarian cancer who have been treated with three or
more prior lines of chemotherapy. Patients are selected for therapy based on an FDA-approved companion
diagnostic designated as BRACAnalysis CDx®. Since then, companion diagnostic test results are also indicated for use
as an aid for identifying patients for targeted therapies that include the drugs Rubraca® (rucaparib) for ovarian
cancer, and Lynparza® (olaparib) and Talzenna™ (talazoparib) for breast cancer in accordance with the approved
therapeutic product labeling. In addition to germline BRCA1 and BRCA2 analysis, tumor-based testing may expand
the population of cancer patients who could benefit from PARP inhibitor treatment. Our laboratory developed the
myChoice® HRD CDx test which uses next generation sequencing for tumor genomic analysis. This panel test
identifies sequence and large rearrangement mutations in the BRCA1 and BRCA2 genes. It also analyzes the incidence
of three types of genomic instability events within a tumor specimen: loss of heterozygosity (LOH), large-scale state
transitions (LST) and telomere allelic imbalance (TAI). These three components are used to generate a Genomic
Instability Score (GIS) which correlate with homologous recombination deficiency in the tumor. Studies have shown
HRD to be a factor associated with enhanced progression free survival following treatment with PARP inhibitors. The
importance of HRD as both a predictive and prognostic biomarker in different cancer settings has been
demonstrated, and continues to be the subject of ongoing studies.
SS 9-B
Integrating Multi-Omics Data for Diabetes Mellitus: Outcomes and ChallengeMark Seielstad (USA)
Professor of Laboratory Medicine, Epidemiology and Biostatistics, and of Global Health Sciences, Institute for Human
Genetics
University of California San Francisco
Type 2 Diabetes is a serious metabolic disorder that is rapidly becoming more common throughout the world.
The causes of diabetes are complex, involving aspects of diet and the environment; together with genetic risk factors.
Two of the most intriguing new developments involve epigenetics (environmentally induced, and partially heritable,
modifications to DNA) and the gut microbiome (the vast bacterial community that plays a central role in human
health and metabolism). Professor Seielstad will use the example of diabetes to illustrate how these complex
interactions between genes and the environment conspire to cause complex human diseases.
SS 9-C
The Promise of Precision Medicine: Molecular Profiling of Neuroendocrine Tumors and Its Clinical Potential
Thanyachai Sura (Thailand)
President
Medical Genetics and Genomics Association (Thailand)
36
Neuroendocrine tumors (NETs) are a rare and heterogeneous group of tumors secreting various hormones
arising from neuroendocrine cells in both endocrine and central nervous systems(1). Approximately one in two
hundred of all cancers originate from neuroendocrine cells. Recent reports from various parts of the world stated
that the incidence of NETs is increasing up to 5/100,000 people per year during the last three decades [2,3]. It
increases with age and peaks between 50 and 70 years. Introduction of the new diagnostic techniques such as radio-
imaging, immunochemical histopathologic examination, genomic testing and/or precision medicine as well as the
update classification system of NETS are considered to be responsible for the increased incidence[2,5]. By its nature,
NETs is a slow growing tumor with heterogeneous clinical presentations and the patients usually seen by multiple
specialists before the correct diagnosis is made. Early diagnosis and specific treatment can save the patients having
NETs. Neuroendocrine tumors (NETs) form in cell that interact with the nervous system or in glands that produce
hormones (2,6,7). NETs are most often found in the abdomen, especially in the gastrointestinal tract (9). These
tumors may also be found the lungs, pancreas and adrenal glands. Some of NETs are genetically determined such
as Multiple Endocrine Neoplasia type I (MEN I), Multiple Neoplasia type 2a (MEN IIa), von Hipple-Lindau (VHL),
Pheochromocytoma, Paraganglioma, Insulinoma,Tuberous Sclerosis Complex (TSC) and Neurofibromatosis type I
(NFI) (7) . Understanding precision medicine is one of the keys for the management of NETs which including punctual
and early diagnosis, specific treatment plan, genetic counseling and prevention of the disease. Patients from
Ramathibodi Hospital with recurrent pheochromocytoma, von Hipple-Lindau and multiple endocrine neoplasia
using the genomic testing for diagnosis, plan of management as well as outcome are discussed.
SS 9-D
Modeling the Aging Process Using Tissue Chips In Space
Associate Director for Special Initiatives, National Center for Advancing Translational Sciences
The aging phenotype in humans is quite complex and heterogeneous, resulting from the interaction of
genetic and environmental factors. Aging is the largest risk factor for numerous human diseases, and understanding
the aging process could facilitate the development of new treatments for age-associated diseases. Aging is marked
by declining tissue function and increased susceptibility to diseases such as cancer, diabetes, cardiovascular disease,
dementia, arthritis, sarcopenia, and renal dysfunction. The use of humans in aging research is complicated by many
factors, including ethical issues; environmental and social factors; and perhaps most importantly, our long natural
life span. Although cellular and animal models of human disease provide valuable mechanistic information, they are
limited in that they may not replicate the in vivo biology. Microgravity has profound effects on the human body from
insights gained from astronauts’ experience and biomedical research conducted onboard the International Space
Station-National Laboratory (ISS-NL). Astronauts in space experience accelerated aging that consists of physiological
changes such as bone loss, muscle deterioration, reduced cardiopulmonary function and immune deficiency. The
changes are attributed to prolonged exposure to microgravity. When astronauts return to Earth, these physiological
changes are often reversed. In collaboration with ISS-NL, the NIH-led Tissue Chips program enables the deployment
of microphysiological systems (MPS) towards improved disease modeling and testing of potential new drugs for
earth-based use. MPS or tissue chips are bioengineered microfluidic cell culture systems seeded with human-derived
primary or stem cells that mimic the histoarchitecture, mechanics and physiological response of functional units of
organs and organ systems. The microgravity-induced changes occur much faster which means tissue chips in space
can model aging associated physiological changes that might take months or even years to happen on Earth. These
tissue chips will allow a better understanding at the molecular, cellular and tissue levels the process of aging, and
translate these findings into improving human health on Earth.
37
Understanding Future Trends of Metagenomics, Proteomics and Metabolomics
SS 10-A
Diagnostic Metagenomics: Applications in the Diagnosis of Dengue Infections
Martin Hibberd (UK)
Professor, Emerging Infectious Diseases
London School of Hygiene and Tropical Medicine
The incidence and geographic range of dengue have increased dramatically in recent decades. Climate
change, rapid urbanization and increased global travel have facilitated the spread of both efficient mosquito vectors
and the four dengue virus serotypes between population centers. At the same time, significant advances in genomics
approaches have provided insights into host-pathogen interactions, immunogenetics, and viral evolution in both
humans and mosquitoes. In this talk I will discuss these advances and the innovative treatment and control strategies
that they are inspiring.
SS 10-B
Asian Microbiome Project: Strains, Functions and Dynamics
Leslie Michelle Dalmacio (Philippines)
Professor, Biochemistry and Molecular Biology
University of the Philippines Manila
In the last decade, characterization of microbial communities in or on the human body has been extensively
done using culture-independent methods or metagenomics and genome sequencing made possible by next
generation sequencing tools and computational analysis. Since the launching of the Human Microbiome Project
(HMP) in 2008 up to its closing in 2017, so much understanding has been gained on the composition of the human
gut microbiota. Several internal and external factors shape the composition of the microbiota of an individual, such
as the initial intestinal colonization at birth, the genetic background of the host, age, lifestyle such as exercise,
smoking, alcohol consumption, environmental and living conditions, onset of metabolic disorders, intercurrent
antibiotic treatments, and on top of all these, diet. As such, the Asian Microbiome Program (AMP) was launched in
2009 to address and highlight cultural differences in the microbiome. The multi-sectoral program includes cohorts
from several Asian countries. The initial projects included children in rural and urban settings. Phase 2 of the AMP
included children in Leyte and showed gut microbiome differences between overweight and obese children living in
Ormoc with those of Baybay. The program is now on Phase IV but continually addresses the effect of diet on the
composition of the gut microbiota, specifically the type of microorganisms being favored by the intake of various
dietary food components like protein, fat, carbohydrate, short chain fatty acids, polyphenols, and other compounds.
38
For AMP Phase IV, the focus is how the diet shapes the gut microbiota of obese and diabetic adults. The multi-
country endeavor requires harmonization of subject inclusion criteria and sampling protocols. Close coordination
among the country investigators are facilitated by periodic meetings. Standardization of procedures is addressed by
having samples processed in a central facility. With these in place, the program aims to provide the gut microbiome
data for the Asian population.
SS 10-C
miRNAs-C19MC regulate the proliferation, invasion and migration in SKBR3 cell lines
Aristizabal-Pachon, AF1,2,3 Gonzalez-Santos J1 Barreto Sampaio GE1
1
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C,
Colombia
The placenta is a tissue with the ability to proliferate and invade the myometrium, using similar ways to
molecular mechanisms that tumor cells use in tumorigenesis process. Many studies have revealed numerous genes
are involved in early migration and invasion steps of the metastatic process and shared with placental development.
In the last years, many studies have indicated that these genes come under strong expression modulations by
microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate post-transcriptionally gene expression
binding in 3 'UTR region of gene target. In this context, the cluster of miRNAs-C19MC involves 46 miRNAs that show
exclusive expression in placental tissue, as previously demonstrated by different groups. Some gene targets of
miRNA-C19MC cluster have been characterized in many cancer types since they stimulate cell proliferation by
apoptotic inhibition and promote cell migration and invasion. However, it is unclear the role of miRNAs-C19MC
cluster members in tumor process. The goal of this study was to identify the biological function of the miRNAs-
C19MC cluster in breast cancer development. A set of C19MC miRNAs cluster was transfected into SKBR3 cell line to
its high expression. After transfection, it was performed clonogenic, migration and invasion assays to determine the
biological role of miRNAs-C19MC cluster in breast cancer cell line. The results showed a significant decrease in
number of colony-forming (p<0.05), a highly significant decrease of migration, and invasive potential (p<0.001). The
bioinformatic analysis showed the miR-C19MC acts through targeting of CDKN1A/p21, PTEN, AKT3, TIMP2, CD44,
TGF-β and nodal signaling, thus block cell survival, invasion and metastasis in breast tumor cells. Our results provide
clear evidence of functional role of miRNAs-C19MC cluster in breast cancer cell line. Other cell lines must be
investigated to confirm the role of the miRNAs-C19MC in the tumorigenesis process.
SS 10-D
SINEUPs: a new antisense, long non-coding RNA-based platform to increase endogenous protein levels for
therapy.
Espinoza S1, Bon C1, Pierattini B2, Jones MH3, Luffarelli R4, D’Agostino S1, Valentini P1, Matey A2, Condò I4, Cotella D5,
Santoro C5, Zucchelli S5, and Gustincich S1
1
Istituto Italiano di Tecnologia, Genova, Italy.
2
Area of Neuroscience, SISSA, Trieste, Italy.
3
Transine Therapeutics, Cambridge, United Kingdom.
4
Department of Biomedicine and Prevention, Laboratory of Signal Transduction, University of Rome “Tor Vergata”,
Rome, Italy.
5
Dipartimento di Scienze della Salute, Universita’ del Piemonte Orientale, Novara, Italy
SINEUPs represent a new platform to increase endogenous protein levels of target mRNAs for therapeutic
purposes. They are antisense long non-coding RNA (lncRNAs) that stimulate translation of sense mRNAs. Their
activity depends on the combination of two domains: the overlapping region, or binding domain (BD), dictates
SINEUP specificity, while an embedded inverted SINEB2 element acts as effector domain (ED) controlling the
enhancement of mRNA translation. Their modular structure can be employed to artificially engineer their BD and
design synthetic SINEUPs to specifically enhance translation of virtually any target gene of interest. They usually
39
increase target protein expression of 2-3 fold, thus representing a more physiological effect than the typical gene
therapy approach. Moreover, they are active only on cells that express target mRNAs, thus limiting the side effects.
As representative examples, SINEUP-GDNF RNA increases endogenous GDNF protein levels both in-vitro and in-vivo,
when injected in the mouse striatum. Furthermore, 6 months after injection, SINEUPs-GDNF protects mice in a
neurochemical model of PD. SINEUP-frataxin RNA increases endogenous frataxin protein levels restoring
mitochondrial activity in Freidreich’s Ataxia patient’s cells proving SINEUPs as a therapeutic strategy for
haploinsufficiencies.
SS 10-E
Preliminary Investigation on the Role of Canonical and Novel, Non-hotspot KRAS Mutations in Metabolic
Reprogramming
Joelle Noriko Galang, Charles Christopher Bataclan, Marian Abigaile Manongdo
and Reynaldo L. Garcia
Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology,
University of the Philippines Diliman, Quezon City 1101
Studies on metabolic reprogramming provide a definitive set of changes that can be investigated in addition
to genetic and histological heterogeneity of tumors. Metabolic reprogramming as a result of oncogene-directed
events is observed in cancer cells allowing them to support proliferation, survival, and invasion by generating
sufficient ATP and biomass components. The aim of this study is to investigate the metabolic perturbations induced
by canonical and novel, non-hotspot KRAS mutations identified from Filipino colorectal cancer patients. Constructs
used include wild type, 2 canonical mutant controls (G12D and G13D), the E63K mutant from COSMICdb, and 4 novel
mutations (E31D, G12S, Y137C, and A59T) – all of which had been previously characterized for their effects on various
cancer hallmarks. Gene expression analyses via RT-qPCR was performed targeting glucose transporter (GLUT1),
amino acid transporters (ASCT2 and LAT1), and asparagine synthetase (ASNS). This was followed by luminescence-
and fluorescence-based assays to measure glucose consumption, glutamine consumption, and LDL uptake. Initial
gene expression analyses via RT-qPCR show an increase in glucose transporter (GLUT1) and amino acid transporters
(ASCT2 and LAT1) mRNAs, upon transfection of KRAS mutant constructs, indicating possible increase in uptake of
corresponding oncometabolites. To test for consequent changes in the cancer cell phenotype induced by metabolic
reprogramming, luminescence- and fluorescence-based assays were performed. An increase in glucose consumption
was observed for KRAS G13D, E63K, E31D, Y137C, and A59T using Glucose-Glo Assay. On the other hand, an increase
in glutaminolysis was observed for KRAS G12D and E63K using Glutamate-Glo Assay. Using a fluorescently tagged
LDL analog (BODIPY), there was no apparent effect on LDL uptake. These results suggest that specific KRAS mutations
may be involved in specific pathway changes, but other drivers may be needed to drive the expected phenotypic
change. This study was able to show that for some metabolic pathways such as glycolysis, these KRAS mutations may
play a significant role in inducing metabolic perturbations. It was also observed that for some metabolic pathways
such as glutaminolysis and LDL uptake, KRAS mutations alone may not elicit significant changes. As such, future in
vitro studies on metabolic reprogramming may need to be studied using a cell line with cooperative p53 and c-Myc
mutations which have more recently been shown to be involved in metabolic perturbations.
40
Solving the Brain Enigma: The Value of Genomics in Neuropsychiatric Disorders
SS 11-A
What can peripheral gene expression tell us about autism spectrum disorders (ASD)?
Richard P. Ebstein (Israel)
Professor, China Center for Behavioral Economics and Finance
Southwestern University of Finance and Economics, Chengdu, China
The dearth of pharmacological treatments for ASD has generated research involving the
oxytocin/vasopressin pathways as intervention targets since these two nonapeptides are paramount human social
hormones implicated in the etiology of disorders involving deficits in social cognition especially ASD. Coincidentally,
the notion has been suggested (Best et al, 2015) of an intriguing relationship between generation of novel ideas for
creative problem solving that may be an adaptive advantage associated with autistic traits. Both oxytocin-OT- (De
Dreu et al, 2014) and dopamine (Flaherty et al, 2005) underpin creative thinking. Towards examining the role of
neural gene pathways in contributing to creative thinking (CT) and its relevancy to ASD, we examine gene expression
for oxytocinergic (CD38, CD157) and dopaminergic (DRD2, COMT) expression in saliva samples and controlling for
Openness to experience, fluid intelligence, and sex. CD38 and its homologue CD157 (BST-1), contiguous gene
duplicates on human chromosome 4 (4p15), represent a gene family that regulates cellular interactions. Importantly,
an OT analogue has long lasting effects on anxiety behavior in a CD157 knockout mouse and communication
impairment during the suckling period is restored by oxytocin in the CD157 knockout (52). CD157 and CD38
knockouts show decreased plasma oxytocin levels suggesting a role for both, CD157 as well as CD38 in OT release
and thus as putative regulators of social cognition. Consequently, we chose to examine both homologues in the
current investigation. The use of peripheral biomarkers, and gene expression in particular, to better understand the
combined role of genes, their pathways and environment, is gaining traction in clinical psychiatry and psychology ,
neurology and drug discovery. Saliva has been characterized as the “mirror of the body” and the “perfect medium
to be explored for health and disease surveillance”. OT is associated with CT and release of OT depends on ADP
ribosyl-cyclases (CD38 and CD157). Moreover, CT and OT neural mechanisms are supported by brain dopaminergic
(DA) pathways. Towards a better understanding of the neurobiology of CT, we evaluated the roles of CD38, CD157,
dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) peripheral gene expression in a non-
clinical population. Two established correlates of CT, trait Openness and fluid intelligence as well as age and sex
were included in the regression model. In women, significant main effects (p<0.01) were positively associated with
gene expression of CD38, CD15, and their interaction CD38 x CD157. The full model (OT and DA gene expressions,
Openness, and fluid intelligence) explained a sizable 39% of the variance in females for the total CT score. In
conclusion, we show that OT and DA gene expression contributed significantly to the CT phenotype suggesting the
notion that the perspective gained from examining the peripheral transcriptome meaningfully added to
understanding the molecular landscape of CT and its relationship to deficits in social cognition characteristic or ASD
especially in women.
41
SS 11-B
Solving the Mystery of the Genetic Cause of X-Linked Dystonia-Parkinsonism: An Integrative Genomics for Rare
Neurologic Diseases
Aloysius Domingo (USA)
Postdoctoral Research Fellow, Center for Genomic Medicine
Massachusetts General Hospital
X-linked Dystonia-Parkinsonism (XDP) is an adult-onset neurodegenerative movement disorder that has so

far only been described in individuals with Filipino ancestry. The genetic cause has been attributed to seven disease-
specific changes (DSCs) observed in all cases on Xq13.1. This XDP haplotype is fully penetrant in males, none of the
DSCs have annotated functions, and all previous studies have suggested that the region is recalcitrant to
recombination. The causal mechanism has thus remained elusive. We sought to definitively identify the causal locus
and functional mechanism of this disease using integrative genomics methods in patient-derived and genome-edited
induced pluripotent stem cell (iPSC) models. We aggregated specimens from 792 Filipino individuals (403 affected
males, 23 heterozygous carrier females, 352 unaffected individuals, and 14 non-manifesting carriers) and developed
fibroblast lines (n=45) and an iPSC resource from 12 XDP patients and their unaffected relatives, including
differentiation to neuronal lineages. We then integrated genome and transcriptome assembly methods using six
technologies (Illumina whole-genome sequencing [WGS]; 10X Genomics assembly; DNA capture sequencing
[CapSeq]; RNA CapSeq; Pacific Biosciences long-read RNA CapSeq, total RNAseq). Genomic analyses detected all 7
DSCs and 47 additional XDP-associated variants (54 total). Haplotype reconstruction further revealed five
recombination events and eight derivatives of the most common haplotype in this cohort, suggesting that
recombinations occur regularly in XDP, and narrowing the critical locus to a region that included the gene TAF1 (TATA
box-binding protein-Associated Factor 1; Transcription Factor IID) exclusively. Transcriptome assembly and
expression analyses discovered a transcriptional signature associated with XDP in TAF1 that involved aberrant
splicing and intron retention that terminated in proximity to an intron 32 SINE-VNTR-Alu-type (SVA) insertion and
negatively correlated with TAF1 expression in XDP probands. The hexameric repeat in this SVA was found to be
variable among probands, ranging from 35-52 repeats, and inversely correlated with age at onset of XDP (r2=0.5).
Remarkably, CRISPR/Cas9 excision of the SVA rescued the aberrant splicing signatures and normalized overall TAF1
expression in XDP cells. All these lines of evidence implicate TAF1 dysfunction, and in particular the insertion of an
SVA in intron 32 of the gene, as the genetic cause of XDP. Our study further serves as an exemplar for the utility of
collaborative effort and integrative genomics in determining the cause and functional mechanism associated with
rare neurologic disease.
SS 11-C
Regulation of the neurofibromin 2 by microRNAs: roles in nervous system tumors and other malignancies
Reynaldo L. Garcia, PhD MPhil (cantab) and Krizelle Mae Alcantara
Disease Molecular Biology and Epigenetics Laboratory
National Institute of Molecular Biology and Biotechnology
University of the Philippines Diliman, Quezon City 1101, Philippines
Inactivation of the neurofibromin 2 gene and the consequent downregulation of its encoded protein Merlin
lead to the development of benign tumors of the nervous system in the genetic condition known as
neurofibromatosis type 2 (NF2). Hallmark symptoms of classic NF2 include bilateral vestibular schwannomas,
meningiomas and ependymomas. In the past, most studies on the molecular biology of NF2 focused on inactivating
inherited and de novo mutations within the gene’s coding region, understandably because all people with the
condition have a mutation in the gene. Much less attention has been given to the role of the wild type protein Merlin
in normal cell physiology. Merlin is a regulator of the actin cytoskeleton and controls functions such as cell
morphogenesis, adhesion and migration. Merlin is also a bona fide tumor suppressor and regulates signaling
pathways controlling cellular proliferation and cell survival. More recently, the wider role of Merlin in tumorigenesis
42
has become more apparent. Rare somatic mutations not associated with neurofibromatosis type 2 have been
identified in common malignancies such as lung, breast and colorectal cancer, melanomas and mesotheliomas.
Further, tumors with no NF2 mutations and with normal NF2 transcript levels, but with low Merlin protein
expression, have been reported. The latter highlighted that dysregulation, and not just deleterious mutations in NF2,
can lead to tumorigenesis. Mechanisms such as promoter hypermethylation and proteasomal degradation, however,
are not consistently observed in malignancies with downregulated Merlin expression, hinting at additional
mechanisms by which the neurofibromin 2 gene or its encoded protein may be regulated. In this study, we
demonstrate that NF2 is subject to microRNA (miRNA) regulation through direct targeting of the cognate miRNA
binding sites in the 3’UTR of the gene, as confirmed by three lines of evidence: (1) Dual‑Luciferase assays in human
colorectal carcinoma (HCT116) and lung adenocarcinoma (A549) cells revealed downregulation of NF2 by miR-92a-
3p via its wild-type 3'UTR, but not NF2‑3'UTR with mutated miR‑92a‑3p miRNA binding site. (2) HCT116 cells
overexpressing miR‑92a‑3p exhibited significant downregulation of endogenous NF2 mRNA and protein levels. (3)
This was rescued by co-transfection of a target protector oligonucleotide specific for the miR‑92a‑3p binding site
within NF2‑3'UTR. Further, miR‑92a‑3p overexpression in HCT116 and A549 cells promoted cell migration,
proliferation and resistance to apoptosis, as well as cytoskeletal disorganization, compared with controls.
Knockdown of the gene by siRNA phenocopied the oncogenic readouts of miR‑92a-3p overexpression in both
HCT116 and A549 cells. These results confirm the unappreciated role of miRNAs in NF2 regulation and clarifies the
role of Merlin in normal cell physiology and why its inactivation or downregulated expression may lead to
tumorigenesis.
SS 11-D
Brain-on-a-Chip: Human Induced Pluripotent Stem Cells (hIPSCs) as An Ex-vivo Tool for Genetic Classification
and Personalized Medicine
Hans van Bokhoven (Netherlands)

Head, Molecular Neurogenetics Unit
Human Genetics Department, Radboudumc Nijmegen
The sequencing power of current next generation sequencing (NGS) technologies permits the study of the
mechanism of diseases and the development of rational intervention strategies. The use of induced Pluripotent Stem
Cells (iPSCs) derived from patients permits to relate molecular signatures to a clinically characterized phenotype.
Differentiation of these iPSCs into neural lineages (excitatory cortical neurons, inhibitory neurons, dopaminergic
neurons) allows us to obtain homogenous monolayers of electrophysiologically active neuronal populations, which
can be non-invasively investigated for intrinsic neuronal properties such as spontaneous electrical activity, by micro
electrode arryas (MEA). During culturing, neurons derived from healthy control subjects form functional,
synaptically-connected, control neuronal networks, exhibiting patterns of synchronized and rhythmic activity on
MEAs. Our previous data show that patient-derived neuronal networks of patients with intellectual disability and
autism show patterns of neuronal network communication that are altered as compared to control networks.
Strikingly, the patterns of mutant networks show deviations in their spontaneous network activity that are specific
for the underlying gene defect. Thus, such gene-specific profiles can be used to classify variants of unknown
significance that are found upon NGS analyses. Moreover, deviant MEA profiles observed in patient-derived neurons
can be used for testing the efficacy of medication. We have pioneered this concept in a small drug screen using
iNeurons for specific neurodevelopmental disorders, which has revealed candidate compounds that we are currently
testing in a mouse model. In addition, we aim to use the “brain-on-a-chip” technology to overcome the limitations
of the current pre-clinical epilepsy models by analysis of the impaired neuronal network and the evaluation of anti-
epileptic drugs (AED) on neuronal dysfunction. As a proof-of-concept model we are using iNeurons from genetically
defined Dravet syndrome patients with a known response to AED medication.
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Disorders of Sexual Development: Integrating Clinical and Genetic Approaches
SS 12-A
Evaluation of Disorders of Sexual Development: Existing Practices and Novel Gene Breakthroughs

Director, Center for Rare Disease and Newborn Screening
Vietnam National Children’s Hospital
The disorders of sex development (differences of sex development - DSD) is defined by congenital
conditions in which development of chromosomal, gonadal, or anatomical sex is atypical (Hughes et al. 2006). DSD
represent a major pediatric concern due to the difficulty of clinical management of these complex disorders. The
aetiology of DSDs is very heterogenous and most often a breakdown of the complex network of gene regulation
responsible for development of testes or ovaries in the embryo, or defect of hormones regulating sex development.
There is also a large numbers of congenital malformation affecting the abdominal wall and perineum that cause
genital deformity. A precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive,
gonadal cancer, psychosocial and quality of life issues. In this report, we will highlight approach, diagnostic algorithm,
for the clinical assessment and molecular diagnosis of a patient with DSD. The current consensus statement on DSD
including caring for individual with DSD developed by a European multidisciplinary group of experts, summarizes
evidence- based and experience- based recommendations will be discussed. Research has been driven by the need
to improve outcomes for children with DSD, and has focused on understanding underlying genetic mechanisms of
DSD. It has also yielded improved methods for diagnostic testing including next generation sequencing (panel, whole
exome and whole genome sequencing) and micro-array. Genetic pathways including currently known DSD genes;
old genes, new functions; novel genes, new pathways will be mentioned.
SS 12-B
Differences of Sex Development (DSD): Pivotal Roles of Laboratory Genomics in Diagnosis, Management,
Medical Education, and Research
Ina Amarillo (USA)

Associate Professor of Pathology and Immunology and Associate Molecular Director Cytogenetics and Molecular
Pathology Lab
Division of Laboratory and Genomic Medicine
Washington University School of Medicine in St Louis
Laboratory genomics has evolved from conventional low-resolution methods to high-definition molecular
assays. The utilization of comprehensive clinical genomics has transformed the landscape of medical care for many
complex human conditions including DSD (Differences of Sex Development). Historically, DSD conditions are
44
genetically diagnosed through karyotype analysis, fluorescence in situ hybridization (FISH), and/or polymerase chain
reaction (PCR) using peripheral blood samples, i.e. identification of sex chromosomes and the presence of SRY or Y
material. Adoption of more advanced genomic technologies such as chromosome microarray analysis (CMA) and
whole exome sequencing (WES) as clinical diagnostic tools has led to the improved detection of the underlying
genetic etiologies of some of the most elusive conditions of DSD. Extension of these high resolution analyses to
include epigenomics profile studies resulted in the identification of regions that may be involved in dysregulation of
sex determination and sex differentiation, e.g. CpG islands, DNA and histone methylation, long-range regulatory
regions. Analysis of genes in pathways associated with sex development has provided a global view of genetic
interactions. Despite such advances, existing clinical WES and CMA methods have limited sensitivity for detecting
non-coding regions and copy number variations (CNV) smaller than the arbitrary cutoff size (e.g. 25 kb), respectively.
To address such limitations, whole genome sequencing in combination with abovementioned assays is currently
being validated in our institution. A subset of DSD patients ultimately develop gonadoblastomas and other types of
germ cell neoplasms, however, relatively little is known about how to identify the subset of patients at risk.
Genomics testing on gonadal tissues or other affected reproductive tissues to assess such risks has been emerging
and being developed as a standard clinical test in our institution as well. To keep up with the advances in
technologies, we have developed approaches to ensure genomics literacy among medical providers and trainees
(medical students, residents, fellows) and expanded efforts to improve understanding of the clinical applications of
various genomics tests in patient diagnostics. Having a multidisciplinary DSD clinic and research teams provide a
venue not only for patient care but also for academic and research opportunities, as well as advocacy.
SS 12-C
Gender Assignment and Counseling for Disorders of Sexual Development

Sultana Faradz (Indonesia)
Professor of Medical Genetics, Director of Center for Biomedical Research
Faculty of Medicine, Diponegoro University
Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal,
gonadal, or phenotypical sex. The clinical, cytogenetic, and molecular studies should be carried out for establishing
the diagnosis of 3 classified DSD i.e. Chromosomal DSD; 46, XX DSD; and 46, XY DSD. In patients with a DSD, the
internal and external sex organs are developed atypically. As a consequence patients may be born with ambiguous
genitalia and may develop gender dysphoria later in life; therefore they require thorough and careful psychological
assessment. Early diagnosis of DSD is essential for proper clinical management, appropriate sex assignment and
better quality of life. The sex assignment of infants and children with DSD must be based on the correct diagnosis.
Diagnosis disclosure, sex assignment and social stigmatization become major dilemma and challenge for genetic
counselor toward DSD cases. Moreover parents or adult patients pursue gender affirmation therapies either
hormonal or surgery to achieve a physical concordance with their parent wish or self-identified gender.
Comprehensive management or collaboration involving various specialists, such as geneticist, endocrinologists and
urologist, would facilitate decision making regarding hormone therapy and surgery. Genetic counselors should also
consider when it may be appropriate to do genetic testing for DSD and gender reassignment. For determining sex
assignment, parental backgrounds and expectations, family personal relationship, social condition and ethnic or
cultural influences should also be considered in each case.
45
SS 12-D
Hormonal and Genotypic Profiles of Individuals Carrying Mutations at SRD5A2 Gene
Nanis S Marzuki,1 Firman P Idris,1 Hannie Kartapradja,1 Alida Harahap,1 Jose RL Batubara2
1
Eijkman Institute for Molecular Biology, Jakarta, Indonesia
2
Departement of Child Health, Faculty of Medicine, Universitas Indonesia
The 5 alpha-reductase type 2 deficiency (5ARD2) is an autosomal recessive genetic disorder causing variable
degree of undervirilisation in external genitalia of affected 46,XY individuals. The diagnosis of 5ARD2 is mainly
established through molecular analysis of SRD5A2 gene, since clinical and hormonal profiles are not specific. In our
country the molecular analysis for SRD5A2 gene is limited and considered expensive. Therefore, the clinical profiles
of individuals carrying mutations at SRD5A2 gene should add some contributions to lead the diagnosis of 5ARD2
gene. The aim of this study is to determine the clinical and hormonal profiles of carriers of SRD5A2 gene mutations.
Families (parents, siblings, grandparents, uncles, or aunties) of 46,XY DSD (disorders of sex development) individuals
were categorized into carriers and non-carriers groups based on SRD5A2 gene analysis, and compared for their
clinical, testosterone/dihydrotestosterone and urinary etiocholanolone/androsterone ratios. There was a total of
102 subjects included, 53 were in the carrier group, and 49 non-carriers. Thirteen variations at the SRD5A2 gene
were detected, 8 were never been reported in other populations. There were no significant differences in age, sex,
pubertal and marietal states, and amount of children between the two groups. The
testosterone/dihydrotestosterone ratios were not significantly different 6.7 (0.30–500.00) vs 4.6 (0.31–30.77,
p=0.443), while the urinary etiocholanolone/androsterone ratios were significantly different between two groups
1.28 (0.08–17.56) vs 0.76 (0.1–5.4), p<0.001). The urinary etiocholanolone/androsterone cut-off for determining
carriers for 5ARD2 were 0.99 with an accuracy of 70%. The urinary etiocholanolone/androsterone ratio of 0.99 might
lead to a diagnosis of 5ARD2 carriers.
SS 12-E
AR gene mutation analysis of undervirilized 46, XY males in Indonesian population
Nurin Aisyiyah Listyasari1, Achmad Zulfa Juniarto2, Sultana MH Faradz2,3
1
Doctorate Program of Medical and Health Sciences, Faculty of Medicine, Diponegoro University, Semarang,
Indonesia
2
Division of Human Genetics, Center for Biomedical Research (CEBIOR), Faculty of Medicine, Diponegoro University,
Semarang, Indonesia
3
Diponegoro National Hospital, Semarang, Indonesia
The various clinical features of Disorders of Sex Development (DSD) depends on the underlying etiology. As
numerous genes are involved in human sex development, mutations in the Androgen Receptor (AR) gene which can
be inherited in an X-linked manner or de novo, have been known as the leading cause of DSD. The aim of this study
was to investigate the mutations in the AR gene as the cause of 46, XY DSD in our population. We studied 69 index
cases of 46, XY DSD with varying degrees of undervirilization. Genomic DNA was isolated from peripheral blood
leukocytes of all patients and Sanger sequencing results of all eight exons of the AR gene were analyzed. Direct
sequence analysis of the AR gene resulted in characterization of a sequence alteration in twelve patients (17.39%).
All of the pathogenic variants identified (R840H; 902insA; V730M; I603N; P671S; C175G; Q738R) have been reported
previously in patients with androgen insensitivity syndrome. Genetic diagnosis of mutations affecting early gonadal
development is becoming increasingly accessible to clinicians. The impact of molecular analysis for patients with
under masculinization is beneficial on health care services and clinical management. The molecular study of the AR
gene facilitated the understanding of the mechanism of 46, XY DSD and could provide evidence for the genetic and
reproductive counseling of families with inherited DSD.
46
Improving the Landscape of LSD Care through diagnosis and therapeutics
(Genzyme-sponsored symposium)
SS 13-A&B
How to Improve Gaucher Disease Diagnosis: Lessons learned from Gaucher Disease Newborn Screening
Clinical Professor, Department of Pediatrics
National Taiwan University
Gaucher disease (GD) is caused by a hereditary deficiency of glucocerebrosidase (GBA), resulting in

accumulation of glucosylceramide and potentially manifesting as hepatosplenomegaly, and neurologic
manifestations in some patients. In Taiwan, a rare disease registration shows a much lower prevalence of GD
compared to the literature. In addition, the proportion of type II/III patients is high, and the median age of diagnosis
in Taiwan is much younger. After screening for around 1 million newborns, the incidence of GBA deficiency was =~1
in 150,000 (95% CI-1/70,000~330,000), slightly higher than the current prevalence rate through clinical diagnosis.
The most common genotype was still L444P/L444P; however, several novel GBA mutations were encountered. The
plasma level of glucosylsphingosine (lyso GL-1) is a useful biomarker for the diagnosis and monitoring, and
phenotype prediction in our newborn screening scenario, of GD. The difference of GD prevalence between the
population screening and the clinical diagnosis highlight the possibility of inability to make a timely diagnosis with
the non-specific manifestations of GD. Increase the disease awareness and establish access to the diagnosis labs are
necessary to provide patients the best treatment outcomes.
SS 13-E
Screening and Treatment of MPS in Vietnam
Director, Center for Rare Disease and Newborn Screening
Vietnam National Children’s Hospital
The first patients with Mucopolysaccharidosis (MPSs) were reported in Vietnam in 1970s and service for
inherited metabolic diseases (IMDs) including Mucopolysaccharidosis (MPS) was set up at the Northern referral
center of Pediatrics – Vietnam National Children’s Hospital, Hanoi (NCH) in 2004 officially. The aim of this report is
to highlight the database of selected screening for MPS, spectrum of MPS, and management for patients with MPS
in Vietnam. 294 cases from 15 years with suspected MPS were reviewed clinically, screened using urinary total GAGs
analysis and specific GAGs using LC-MS/MS. 109/294 cases were confirmed using enzyme assay and mutation
analysis for MPS I, II, IIIA, IIIB, IVA, VI and VII. Spectrum of subtype of MPS patients is MPS II (53 cases, 48.6%), MPS
IVA (32 cases, 29.3%), MPS VI (10 cases, 9.1%), MPS I (8 cases, 7.3%), IIIA (1 case, 0.9%) , IIIB (5 case, 4.5%) and VII
(1 case, 0.9%). Phenotype and genotype of Vietnamese patients with MPS I, II, IVA, VI will be discussed. ERT were
47
given for 18 patients with MPS (2 cases with Hurler and 16 cases with Hunter disease) since 2014. A expanding
newborn screening laboratory was set up for newborn screening pilot in Vietnam in 2019.
OMICS Technologies for optimized and personalized medicine
(PCHRD-Sponsored Symposium)
SS 14-A
Leptospirosis: mechanistic insights and potential molecular prognosticators
Jose B. Nevado Jr. (Philippines)
Research Professor, Institute of Human Genetics
National Institutes of Health, University of the Philippines Manila
Leptospirosis is an endemic zoonotic disease that has been a significant cause of morbidity, healthcare cost,
and mortality. Although most cases are mild, about 5-10% of cases becomes severe with end-organ complications;
and the mechanisms remains unknown. Recognition the importance of early detection of at-risk patients and the
benefit of preemptive interventions, molecular clues and mechanisms could provide the key to lower adverse
outcomes. With a longitudinal design, we are able to arrive at 3 important findings using profiling of mRNA of
peripheral blood mononuclear cells (PBMCs): prognostic markers, mechanistic inferences, and therapeutic targets.
We have identified networks and molecules that can likely explain the detrimental mechanisms of the disease, and
underscore the possibility of using molecular markers to guide preemptive measure that can reduce adverse clinical
outcomes.
SS 14-B
Single nucleotide polymorphism (SNPs) in Genes of Lupus - A Philippine Study (SIGLA-PH)
Michael L. Tee (Philippines)
Vice Chancellor for Planning and Development
University of the Philippines Manila
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease predominantly affecting women in
their childbearing age. The etiology and pathogenesis of lupus have been studied extensively and have been found
to be multifactorial, with genetic, environmental, ethnic and racial factors playing significant roles in its
development. Susceptibility to lupus has a strong genetic component particularly with single nucleotide
polymorphisms (SNP) that differ across various races. This report by the UP Manila Genetics of SLE Study Group was
conducted to determine the association of selected single nucleotide polymorphisms (SNPs) to susceptibility of
developing SLE. Specifically, the study sought: 1.To estimate the prevalence of genetic polymorphisms among
Filipino SLE patients; and 2.To determine the association of genetic polymorphisms and the risk for the development
48
of SLE among Filipinos. Six hundred and sixty patients were enrolled in the trial: 337 patients who met the 2012
Systemic Lupus International Collaborating Clinics (SLICC) Criteria for SLE and 323 controls. Demographic data were
obtained from the subjects. Candidate genomic variants were derived from various databases and were genotyped
from the subjects’ blood DNA samples using customised microarray platform. Multidimensional scaling, principal
component analysis and structure association analysis were conducted. We analyzed data from 310 SLE patients and
318 controls. Majority of the recruited volunteers, through convenience sampling of consulting patients presenting
at participating clinics, were females (97.1%) and the mean age of SLE diagnosis was 26.71 ± 11.6, reflecting the
known preponderance of SLE. Most patients presented with acute cutaneous lupus manifestations, arthritis, non-
scarring alopecia and oral or nasal ulcers on diagnosis. Majority were positive for antinuclear antibody (ANA). After
filters for missing genotypes and HWE were applied, 647 samples (329 cases and 318 controls) were analyzed for
SNPs. We have identified eight SNPs located in chromosomes 1, 6, 10 and 15 showing significant association with
the onset of SLE. Two of these variants were novel candidate markers of susceptibility. This is the first nationwide
genetic study in Filipino lupus patients, and unique SNP variants in chromosomes 1, 6, 10 and 15 were seen in our
population. These findings have potential implications on the clinical manifestations, complications, screening, and
response to treatment that are unique to our population.
SS 14-C
The Prevalence of Genetic Polymorphisms Associated with the Risk for the Development of Hypertension,
Dyslipidemia and Coronary Artery Disease Among Filipinos
Eva Maria Cutiongco-de la Paz (Philippines)
Executive Director
National Institutes of Health, University of the Philippines Manila
In the Philippines, diseases of the heart and vascular system rank first and second in the list of top ten
causes of death. While traditional risk factors like smoking and obesity are known to contribute to the development
cardiovascular diseases, studies have found that genetics also play a role in the development of heart disease and
its fatal complications. However, most of the researches have been done in other population groups, and
unfortunately, Filipinos are not well-represented in these studies. It has been observed that inter-ethnic differences
exist and it is important to conduct Filipino-specific researches to determine susceptibility to hypertension, high
cholesterol, heart attack and stroke. Filipino adults with hypertension, dyslipidemia and ischemic diseases such as
coronary artery disease and stroke were enrolled in multiple age- and sex-matched case-control studies to
determine whether genetic variants called single nucleotide polymorphisms (SNPs) are associated with susceptibility
to develop these diseases. Genomic DNA was extracted and genotyped for selected single nucleotide polymorphisms
(SNPs). Genetic data cleaning and analysis were done using GenomeStudio and PLINK. Chi-square analysis and
logistic regression analysis were used to determine association of these polymorphisms with cardiovascular diseases.
After analysis, variants in MIA3 and CYP2C19 were noted to be associated with susceptibility to coronary artery
disease and acute coronary syndrome, respectively. A variant of GCKR was noted to be associated with low HDL,
while a variant of CDH13 was associated with mixed systolic and diastolic hypertension. The variants found from this
study may lead to potential biomarkers for early diagnosis of these diseases among Filipino patients. These variants
will also contribute to the knowledge on the different mechanisms on how these diseases develop. Physicians may
find it useful to include genetic testing in future clinical practice guidelines for cardiovascular diseases, after
conducting further researches on the efficacy of genetic tests and economic evaluation of the value of including
genetic testing in standard cardiovascular healthcare.
SS 14-D
Vitamin D Receptor Mutations and Fragility Fractures
Cynthia P. Saloma (Philippines)
Professor, Molecular Biology and Biotechnology
National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman
49
Deficiency in Vitamin D has been associated in fragility fractures. It is a real problem worldwide with its high
prevalence across all regions and population groups. It becomes of even more concerm among the elderly where
higher incidence of hip fractures occur. In some studies, the data suggest that administration of vitamin D alone,
without calcium supplementation is unlikely to reduce the incidence of hip fracture among the elderly in the
community setting or in institutionalized care. In this study, we focused our attention on the status of the vitamin D
receptor (VDR) among older Filipino women with osteoporotic fracture. VDR protein is a nuclear transcription factor
that mediates the action of the active form of vitamin D, and influences calcium absorption, bone remodeling and
mineralization. We looked for possible genetic variants in the entire 101 kb vitamin D receptor gene using targeted
next generation sequencing of a group of 50 post-menopausal women with or without osteoporotic facture seen at
the Philippine Orthopedic Center. All enrolled POC post-menopausal study subjects (n=50) had the following
characteristics at the start of study (a) aged 55 years and above; (b) over 5 years menopause with no occurrence of
menopause at the age of 40 years old and below (premature menopause); (c) menopause not induced after surgery
or cancer treatment; (d) without history of malignant and metabolic bone diseases; (e) non-takers of drugs that
affect bone health such as steroids, heparin, warfarin, cyclosporine, glucocorticoids, medroxyprogesterone acetate
and thiazide diuretics; (f) non- alcohol drinkers (< 3 units/day). We found 1496 unique variants in the whole 101-kb
VDR gene with novel mutations not registered in the dbSNP database. Noteworhty is the discovery of two novel
heterozygous disease-associated frameshift mutations. Targeted NGS was successful in surveying the VDR gene for
polymorphisms correlated with fragility fracture. Through this approach, we were able to sequence thousands of
variants in healthy controls and in postmenopausal patients with fragility fractures. The results we obtained provide
valuable insights in VDR control as well as open the way for interrogating the possible molecular underpinnings
behind inter-individual response to vitamin D treatment for fragility fractures.
Simultaneous Symposium 15
Illumina Genomics Session
SS 15-A
Looking for disease genetic markers among epigenetic profiles
George Anene-Nzelu
Senior Research Fellow, Cardiovascular Research Institute
Department of Medicine, National University of Singapore
Our lab is known for its studies of the cardiac epigenome and its role in heart disease and heart failure. We
have completed profiling a set of human left ventricles (heart failure and healthy controls). Analysis of these reveals
consistent cellular pathways that are well recognised in heart failure pathology. More importantly, we identified a
set of 1,680 enhancer loci whose H3K27-acetylation enrichment was associated to unique genetic variants (SNVs)
50
underlying each enhancer peak. A substantial number of these also bore correlation to gene expression abundance,
sometimes to distally interacting genes that are hundreds of kilobases away, but nonetheless identifiable by cardiac
Hi-C and HiChIP based chromatin connector maps that we have also generated. Population genetic variants at
noncoding enhancer loci may indeed have functional value for disease and phenotype if they perturb TF binding
motifs, leading to chromatin and gene expression differences. Hence, we speculate that some such differences are
silent in the relevant tissue, until the onset of pathogenic stimuli when because of the noncoding genetic variant, a
differential disease response ensues. This mechanism likely underpins an important inter-relationship between
genetics and epigenetics for their relevance to disease and phenotypes. We have now made use of the haQTL dataset
to prioritise GWAS genetic variants for functional validation. The approach of chromatin QTL and 3D connectome
analyses in disease-relevant tissue promises not just to resolve the identity of functional genetic variants, but target
genes with correlated expression changes may be implicated to represent important pathways for new disease
therapy.
SS 15-B
Polygenic risk scores and complex disease
Peter Coleman
Senior Segment Marketing Manager Genetic Health, Asia Pacific Japan
Illumina
Although genome wide association studies (GWASs) have been around for more than 10 years providing
data on population and complex trait genetics1,2, it is only recently that there has been a renewed interest in
polygenic risk scores (PRS). This interest has been facilitated by access to larger GWASs and larger data sets as well
as improved computational methods3. In contrast to monogenic diseases such as thalassaemia and cystic fibrosis
that are caused by a single mutation, common complex diseases such as type 2 diabetes and coronary artery disease
(CAD) are polygenic, multifactorial and often adult-onset. Complex diseases do not follow a specific model of
inheritance and are associated with multiple variants localised inside and outside of coding regions. The variants
associated with the disease can be used to generate a PRS. In some complex diseases PRS could enable early
detection, prevention and intervention, and may be a step towards preventative and personalised medicine through
individual risk stratification. This talk will briefly outline the current state of PRS as well as the challenges that might
be encountered when we consider translational or clinical application of PRSs.
SS 15-C
Polygenic risk scores and breast cancer
Jingmei Li
Senior Research Scientist, Genome Institute of Singapore
Based on current evidence, population-based screening mammography above is recommended every two
years for women aged 50 and above. However, women aged 40 to 49 have to weigh the pros and cons of starting
screening at an earlier age. Many women with no obvious symptoms of breast cancer may be at high genetic risk for
the disease. Polygenic risk scores (PRS), or genetic risk scores, reflect an individual’s aggregate inherited risk for a
complex disease conferred by multiple genetic variants. If relying only on classical non-genetic risk factors such as
family history and number of children to make a decision, many women and their physicians are not benefiting from
the additional knowledge of genetic risk through PRS. PRS in breast cancer has the potential to motivate high-risk
individuals to be more carefully monitored, make lifestyle changes, and get treatment earlier. To assess the wider
clinical application of PRS in our latest work, we assess the performance of various European-derived PRS in
predicting breast cancer among ~8,000 cases and ~8,000 controls of Asian descent. In addition, we highlight some
of the technical challenges in PRS analyses and interpretation of the results for individuals.
51
SS 15-C
Accurate and Accelerated analysis solutions for Illumina NGS data
Yue Ying Tan
Senior Bioinformatics Specialist
Illumina
Illumina has pioneered major advances for sequencing platform simplicity, flexibility, and performance.
Each sequencing platform delivers exceptional data quality and performance, with flexible throughput and simple,
streamlined workflows. In recent years, breakthroughs in sequencing throughput have outpaced our capacity to
process data. In 2018, more than 100 petabytes of data were generated by Illumina systems. To keep up with the
vast amount of data, Illumina recognizes that customers require easy-to-use analysis solutions that can efficiently
translate raw sequencing data into meaningful results. The Illumina analysis solution is engineered with tight
customer collaboration to address the key challenges associated with analysis of NGS data - such as lengthy compute
time and massive volumes of data. Here, we introduce a highly accurate and ultra-rapid secondary analysis solution
delivers high flexibility and cost efficiency, enabling labs of all sizes and disciplines to do more with their genomic
data.
52
The Emerging Role of Enhancers in Gene Regulation
(RIKEN – Sponsored Symposium)
SS 16-A
Overview of the Enhancerome Discovered in the FANTOM
Yoshihide Hayashizaki
Director, Preventive Medicine and Diagnosis Innovation Program
RIKEN Cluster for Science and Technology Hub
Since the year 2000, more than 1000 scientists from various research fields have taken part in the FANTOM
Consortium to analyse omics data produced by technologies that we have developed. This includes a series of
applications of our full-length cDNA technology, and more recently, expression profiling using CAGE (cap-analysis
gene expression). For each phase of the FANTOM project, we generated a large-scale dataset using our technology,
then organized activities through the consortium to turn it into an international de facto standard database, and to
exploit it for many biologically significant discoveries. FANTOM5 project used CAGE technology and it has so far
provided the most extensive human cell maps of the transcriptome, promoters, enhancers and transcriptional
network which deterministically controls cell phenotypes. FANTOM5 cell map covers a wide variety of representative
human cell types, newly identifying more than 200,000 novel promoters and 65,000 enhancers based on the
principle that enhancers which is around a few hundred bases of the genome sequence, have a bidirectional activity
to transcribe eRNAs (enhancer RNA). These enhancer RNA (eRNA) activities are very tissue specific and their
expression patterns can be clustered in a tissue specific manner. From the CAGE data for 180 different cell tumors
issued in FANTOM5, we can predict enhancer-controlled promoters by exploring for promoters that are
synchronously expressed with a high correlation (correlation coefficient from 0.95 to 0.99) with eRNA. Surprisingly,
it was found that there are many responsible mutations (SNPs) in enhancer region that show high odds ratio in GWAS
of various genetic diseases. Many of the enhancer regions that we have found can be very important biomarkers in
the fields of medical and clinical sciences, as a diagnosis of cancer traits, application of molecularly targeted drugs,
and as a new examination area for mutation of disease. In terms of the detection of eRNA, there was a problem that
a signal could not be seen by noise, because of the very short retention time of eRNA. To solve this problem, a new
technology named as “NET-CAGE” that uses CAGE technology for “Nascent RNA” was developed. This technology
will be presented by Dr. Murakawa in this session. In this talk, an overview of FANTOM achievement which developed
a new phase of enhacerome will be presented.
SS 16-B
Novel NET-CAGE Technology Reveals the Dynamics and Topology of Human Cis-Regulatory Elements
Yasuhiro Murakawa
Team Leader, RIKEN-IFOM Joint Laboratory for Cancer Genomics
RIKEN Center for Integrative Medical Sciences
53
Promoters and enhancers are key cis-regulatory elements, but how they orchestrate to generate cell-type-
specific transcriptomes remains elusive. Here we developed a novel Native Elongating Transcript Cap Analysis of
Gene Expression (NET-CAGE) method to sensitively detect 5’-ends of nascent RNAs in diverse cells and tissues,
including unstable transcripts such as enhancer-derived RNAs. By combining NET-CAGE and conventional CAGE, we
studied RNA synthesis and degradation at the transcription start site level, and characterized the impact of
differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without
the influence of RNA degradation, and show that enhancer-promoter pairs are generally activated simultaneously
upon cellular stimulation. We identified many new enhancers with high sensitivity, and delineated primary locations
of transcription within super-enhancers. Our NET-CAGE dataset derived from human and mouse cells and tissues
significantly expands the FANTOM5 catalogue of transcribed enhancers, with broad applicability to biomedical
research.
SS 16-C
Variation and Evolution of Shh Enhancers
Toshihiko Shiroishi
Director
RIKEN BioResource Research Center
Accumulating data support that morphological evolution has been more often driven by changes in cis-regulatory
sequences that control gene expression rather than by changes in sequences that encode protein. We have studied
effect of change of enhancer sequences on morphological evolution, using the Shh locus as a model system, which
encodes a key signaling protein acting on animal morphogenesis. Here, we show a couple of topics on this issue.
First, we show that sequence of an esophageal epithelium-specific Shh enhancer has collapsed during transition
from vertebrate lungs to swim blader, on the other hand a new enhancer sequence was created in parallel. It
indicates the possibility that phase transition of enhancers is involved in the morphological evolution. Next, genetic
study of an old mouse mutant exhibiting syndactyly with interdigital webbing revealed that an insertion of a pre-
existing enhancer located at chromosome 14 into vicinity of the Shh locus in chromosome 5 caused an ectopic
expression of Shh in the interdigital region, which eventualy resulted in the mutant phenotype. Thus, it demonstrates
that translocation of existing enhancer can generate a novel morphology by causing a new expression pattern of
developmental gene. These are good examples that dynamic change of enhancer sequence contributes to
morphological evolution.
Inventing the future: MD-PhDs' Researches on Spotlight
(PCHRD sponsored symposium)
54
SS 17-A
Identification of Leptospira Serogroups Circulating in the Farmer-Animal interface of High-Prevalence Areas
in Cabatuan, Iloilo, Philippines
Pia Regina Fatima C. Zamoraa*
Villanuevab, Glorianib
aCollege of Medicine, University of the Philippines, Manila, Philippines, bDepartment of Medical Microbiology,
College of Public Health, University of the Philippines Manila, Manila, Philippines
*Corresponding Author: prfczamora@gmail.com
Leptospirosis affects people worldwide, especially those in the tropics. Transmission occurs among those
who come in contact with soil or water contaminated with leptospires. Prevalent serovars among high-risk groups
should be identified to update antigenic panels used in immunodiagnosis, and develop vaccines. In the Philippines,
farmers have a high risk of contracting the disease due to occupational exposure. Thus, this study aimed to
characterize Leptospira serovars in the farmer-animal interface of high-prevalence areas in Cabatuan, Iloilo,
Philippines. Barangay Tigbauan Road and Barangay Gines Patag were chosen as study sites. Blood samples were
collected from asymptomatic farmers and animals within their vicinity from October 2017 to February 2018.
Seropositivity among farmers and animals were determined through the Microscopic Agglutination Test (MAT) using
37 live Leptospira strains belonging to 23 serogroups. The seroprevalence rates among farmers and animals were
lower compared to rates reported in studies done in other endemic areas. Based on seropositivity, the possible
infecting serogroups in the areas were as follows: farmers (Autumnalis, Pyrogenes, Hebdomadis,
Icterohemorrhagiae, Javanica, Shermani, Semaranga), water buffaloes (Pyrogenes, Javanica, Pomona, Semaranga),
cows (Grippotyphosa, Javanica, Semaranga), pig (Semaranga), goats (Icterohaemorrhagiae, Shermani, Pyrogenes,
Canicola, Autumnalis, Pomona), dogs (Canicola, Pyrogenes), and rats (Pomona, Autumnalis, Javanica, Djasiman,
Icterohemorrhagiae, Hebdomadis, Semaranga, Celledoni). Despite the lower seroprevalence rates, it was shown
that there were common serovars to which farmers and animals were exposed to in the areas, indicating possible
transmission. In addition, relatively higher antibody titers of 640, 1280, and 2560 were observed among rats (R1,
R39, R 55/57) and goats (G10.1, G43.2) from different locations in the 2 barangays, suggesting a more recent
exposure of these animals to the organism. This study demonstrated possible transmission of Leptospira within the
farmer- animal interface of previously documented high-prevalence areas in Cabatuan, Iloilo, Philippines. In
addition, the results of this study may be used to improve diagnostic tests, and develop a vaccine specific to the
area. Furthermore, similar high-risk exposures and environmental conditions may be seen in other agricultural
municipalities in Iloilo, Philippines, which explains the endemicity of leptospirosis in the province.
SS 17-B
Genetic characterization of epithelial ovarian cancer among Filipino patients in a Philippine tertiary hospital
Ana Joy Padua1, Ryan C.V. Lintao1, Yukiko Nakura2, Michinobu Yoshimura2, Itaru Yanagihara2, Jose Nevado Jr.3,
Erlidia F. Llamas-Clark4
1
College of Medicine, University of the Philippines Manila, Philippines
2
Department of Developmental Medicine, Research Institute, Osaka Women’s and Children’s Hospital, Japan
3
Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila, Philippines
4
Department of Obstetrics and Gynecology, College of Medicine and Philippine General Hospital, University of the
Philippines Manila, Philippines
Ovarian cancer is the fifth most commonly diagnosed cancer in Filipino women, with epithelial ovarian
cancer (EOC) comprising 90% of known cases. Early-stage ovarian cancer is asymptomatic at the outset, and no
effective screening tools are available, resulting in late diagnosis and making it the most lethal gynecologic fatality.
Definitive treatment of epithelial ovarian cancer is debulking cytoreductive surgery with a standard regimen of
platinum-based chemotherapy, however there is heterogeneity in chemotherapeutic response. While a quarter of
cases are associated with genetic mutations in BRCA1/2, most are due to sporadic genetic mutations. In this study,
55
genetic mutations associated with pathogenesis and chemotherapeutic response of epithelial ovarian cancer in
Filipino patients were characterized using targeted next-generation sequencing. Genomic DNA were isolated from
formalin-fixed paraffin-embedded ovarian specimens from 8 chemotherapy-sensitive and 8 chemotherapy-resistant
patients. Next-generation sequencing was done to identify mutations in hotspot regions of common oncogenes and
tumor-suppressor genes. Our pilot study has shown that KDR gene has the most frequent variation in EOC patients.
Unique exonic variants were found in chemoresistant EOC cases, which were predicted to have deleterious protein
modification. A case-control study involving 35 patients was conducted to validate the prevalence of four exonic
mutations unique in chemoresistant ovarian cancer, which were not present in the rest of our samples, indicating
its sporadic nature. To date, this was the first comprehensive genetic analysis done on Filipino ovarian cancer
patients.
SS 17-C
Circulating MicroRNAs as Biomarkers for Hepatic Fibrosis Progression in Schistosomiasis
Ian Kim Tabios1, Yuichi Chigusa2, Mihoko Kikuchi3 and Lydia Leonardo4
1
College of Medicine, University of the Philippines Manila
2
Department of Tropical Medicine and Parasitology, Dokkyo Medical University
3
Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University
4
Institute of Biology, College of Science, University of the Philippines Diliman
Hepatosplenic morbidities due to chronic schistosomiasis japonica remain prevalent in endemic areas of
the Philippines. Host miRNAs have been shown to play important regulatory roles in the pathologic response to
schistosome infection. The study aimed to analyze selected circulating miRNAs in sera of Filipino patients. A
prospective longitudinal study design with purposive sampling was employed in Leyte. Patients were examined at
baseline and at 12 months after praziquantel treatment. A comparison of the expression profile of selected
circulating serum miRNAs between schistosomiasis-infected individuals with varying severity of ultrasound-
detectable hepatosplenic pathology and healthy controls was done. A total of 75 individuals were recruited for the
longitudinal study from the initial 895 people examined in the cross-sectional study. At baseline, 31 patients had
typical network hepatic fibrosis (T3), 17 had mild and atypical hepatic fibrosis (T1&2), and 27 had no ultrasound
detectable fibrosis in the liver parenchyma (T0). Repeat examination 12 months after praziquantel treatment
showed persistence of fibrosis in all T3 patients and in 23.5% of patients with initial T1&2. Among initially T0 patients,
development of fibrosis to T1&2 was seen in 18.5% of cases. Progression of fibrosis was observed in 11.8% of initially
T1&2 patients. Reversal of fibrosis was recorded in 64.7% of patients with initial T1&2 fibrosis. The expression levels
of miRNA-150-5p, miRNA-93-5p, and miRNA-146a in serum were significantly different in patients with T0 fibrosis
compared in those with T1-3 (P < 0.0001, < 0.0001, and = 0.0229) while the expression levels of miRNA-122 and
miRNA-200b-3p showed no significant difference between the two groups. In the longitudinal analyses relating
baseline miRNA levels with changes in hepatic fibrosis from baseline to 12 months after PZQ treatment, both miRNA-
150-5p and miRNA-93-5p were not significantly different among the groups. This study provides initial evidence for
the potential use of circulating serum miRNAs in the diagnosis of the severity of schistosomiasis liver disease.
SS 17-D
Metagenomic Profiling of Gut Microbiome Among the Risk Groups of Atherosclerotic Coronary Artery Disease
Mark Joseph M. Abaca1, Aldons J. Lusis2, Paul Ferdinand M. Reganit1,3, Leslie Michelle M. Dalmacio1
1
College of Medicine, University of the Philippines Manila
2
David Geffen School of Medicine, University of California Los Angeles
3
Section of Cardiology, Department of Medicine, Philippine General Hospital
The study aimed to determine the association of human gut microbiome with the risk status of
atherosclerotic coronary artery disease (CAD) specifically, to compare the gut microbiome structure and function of
individuals in the different risk status of CAD. The study involved patients from the Philippine General Hospital at
low risk (LR) (n=10), at high risk (HR) (n=10), and with CAD (CD) (n=10). The taxonomic and functional profiles of the
56
gut microbiome was determined using Illumina MiSeq shotgun sequencing. Data were analyzed using Kruskal-Wallis
H test and multiple pairwise comparison by Mann-Whitney U test. Bacteroidetes (68.67%) and Firmicutes (25.10%)
were the dominant phyla in the gut microbiota of Filipino adults. The gut microbiota of the participants at high risk
and with CAD were abundant with Proteobacteria (LR vs HR, p=0.045; LR vs CD, p= 0.021) and Enterobacteriaceae
(LR vs HR, p=0.049; LR vs CD, p=0.034). Bacteroides (p=0.049) was abundant among individuals with CAD only.
Although lacking statistical significance, Bifidobacterium (p=0.125) and Lactobacillus (p=0.659) were seemed to be
more abundant in the gut microbiome of individuals without CAD. There was a non-significant increase in the alpha
diversity measured by Shannon index (p=0.298) of the gut microbiome as the risk of CAD elevates. Functional
profiling showed that genes corresponding for cellular housekeeping functions and metabolic pathways were
enriched in the gut microbiome of Filipino adults. Microbial genes for nitrogen utilization (p=0.012), DNA repair
(p=0.044), and DNA conformation change (p=0.034) were more abundant with low-risk gut microbiome while,
transport of nutrients (p=0.044), harnessing of energy from dietary sources (p=0.038), cell wall component
biosynthesis (p=0.037), phosphorylation (p=0.036), signal transduction (p=0.043), response to chemicals (p=0.026),
and biosynthesis of specific amino acids, such as lysine (p=0.014) and glutamine and glutamate (p=0.028), and
phospholipids (p=0.038) appeared to be enriched with the increased risk of atherosclerotic CAD. The study showed
that increasing risk of atherosclerotic CAD parallels alterations in the gut microbiome, both in taxonomic
composition and functional capacity. It was demonstrated that gut microbiome profiles of high-risk differed from
low-risk individuals but, resembled those of with CAD. The findings suggest that perturbations in the gut microbiome
diversity occur early in the development of atherosclerosis. Overall, gut microbiome profile may be related to the
risk status of CAD and may predict atherosclerosis. However, further studies with larger number of participants are
required to confirm these observations.
SS 17-E
Gene expression analyses of CIDEC and S100A4 in Metastatic Human Papillary Thyroid Carcinoma
Charles Patrick D. Uy1*, Reynaldo L. Garcia2, Jose B. Nevado3
1
University of the Philippines Manila, College of Medicine,
2
National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman,
3
Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila
This study aimed to identify and characterize novel molecular markers correlated with metastasis in
papillary thyroid carcinoma. This study made use of online gene expression (RNA-seq) database and Weighted Gene
Correlation Network Analysis (WGCNA) to identify highly correlated genes (modules) with metastasis, survival and
recurrence. Gene candidates from these modules were identified based on their module membership (correlation
to other genes in the module) and gene significance (correlation to clinical trait of interest) scores. Candidate
modules have the highest correlation to the clinical traits and subjected to gene ontology enrichment. Final gene
targets were functionally tested in vitro using K1 papillary thyroid cancer cell lines through scratch wound assay and
phalloidin (actin) staining. Using online data to make a gene co-expression network, 3 significant modules related to
disease stage, survival status and disease-free status were chosen (p<0.05). These modules were related to oxygen
transport, AKT signaling and cGMP signaling respectively (p<0.05). From these modules, five candidate genes (CIDEC,
S100A4, PTPRH, TRPV2 and KLRC3) relevant to PTC aggressiveness were found. Of these, Module 1 and its genes,
CIDEC and S100A4 were chosen for in vitro assays. In the scratch wound assay of K1 PTC cells, CIDEC expressing cells
had higher wound closure rates compared to empty vector controls only in 2% serum (p<0.05), while S100A4
expressing cells had decreased rates regardless of serum concentration (p<0.05). In individually tracked cells, higher
motility rates were seen in CIDEC and S100A4 overexpressing cells in 2% serum concentrations compared to the
empty vector control not seen in higher serum concentrations (p<0.01). Phalloidin staining showed that CIDEC
transfected cells developed possible actin fiber organization compared with empty vector control (p<0.05). In
contrast, S100A4 overexpressing cells, lacked actin organization. These results suggest potential metastatic
influences in overexpression of CIDEC and S100A4 in PTC which may have implications in prognostication and
therapeutic directions.
57
SS 17-F
Identification of Alpha Globin Gene Mutations in Filipino Newborns Diagnosed with Alpha Thalassemia
Mark John Girasol1, Terence Diane Fabella2, Catherine Lynn Silao2,3
1
MD-PhD in Molecular Medicine Student, College of Medicine, University of the Philippines Manila, 2Institute of
Human Genetics, University of the Philippines – National Institutes of Health, 3Department of Pediatrics, University
of the Philippines - Philippine General Hospital
Alpha thalassemia is an inherited autosomal recessive disorder that comprises all conditions where
production of hemoglobin alpha chains is deficient or absent. It is characterized by abnormal hemoglobin with
hypochromic, microcytic anemia in the absence of iron deficiency. Disease phenotypes depend on the number of α-
globin genes affected and, sometimes, the type of mutation (e.g., deletional vs. non-deletional). Currently, there is
no centralized registry for alpha thalassemia in the Philippines, and carrier frequency is also unknown (all these in
the context where malaria is endemic, and carriers are positively selected). Population studies have indicated that
the spectrum of α-globin gene mutations is heterogeneous and population-specific. Therefore, it is difficult for
epidemiologists to classify which among the phenotypic characteristics superimpose specific underlying aberrant
genotypes only by crude utility of hematologic indices. Knowledge of the variants present in Filipino population can
lead to the tailoring a Filipino-specific carrier screening (and diagnostic) kits, which can offer a highly sensitive and
specific screening procedure at a much lower cost. In tandem with evidence-based genetic counseling, this can lead
to better disease management and decrease in disease incidence altogether. This study identified non-common and
novel mutations in α1- and α2-globin genes (HBA1 and HBA2, respectively) of αα/--SEA (heterozygous for Southeast
Asian deletion mutation) Filipino newborns, as determined by the Alpha-Globin SEA StripAssay and referred by the
Expanded Newborn Screening Program. DNA samples from 20 Filipino newborn patients underwent semi-nested
polymerase chain reaction (snPCR) where HBA1 and HBA2 were amplified into two overlapping segments. snPCR
products underwent bidirectional DNA sequencing to determine mutations. Sequence analysis of HBA1 and HBA2
genes of αα/--SEA newborn patients revealed a total of five base substitutions in the HBA2 gene, three of which are
known single-nucleotide polymorphism. A novel missense mutation and the Hb Evora variant are likely to affect
alpha globin’s stability. RNA quantification and biosynthesis assays may be helpful in determining if these variants
are transcribed, if their transcripts remain stable enough to be translated, and if their translated products persist as
precipitated chains or are degraded shortly after biosynthesis. With the current diagnostic techniques that rely
heavily on the physicochemical properties of aberrant hemoglobin as well as the detection of a limited number of
mutations, these hyperunstable hemoglobin variants and determinants can easily be missed. Since the effects of
non-deletional mutations are generally more severe, detection of carriers harboring these non-common mutations
becomes a principal concern.
SS 17-G
Role of Hypoxia-induced Factor 1A (HIF1A) on Intermittent Hypoxia-induced Adipose Tissue Dysfunction in Type
2 Diabetes Mellitus
Josept Mari Poblete1,3,4, Shengying Bao3,4, Jose Nevado, Jr1,2, and Ulysses Magalang, MD3,4,5
1
College of Medicine, University of the Philippines Manila, Manila, Philippines
2
Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila
3
Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio
4
Division of Pulmonary, Allergy, Critical Care and Sleep, Department of Internal Medicine and
5
Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio
Obstructive sleep apnea (OSA) commonly coexists in type 2 diabetes mellitus (T2DM) patients, but the
mechanism for this overlapping epidemic remains unclear. We hypothesized that the intermittent hypoxia (IH) in
OSA leads to upregulation of hypoxia-inducible factor 1a (HIF1A) in adipose tissue (AT), leading to local fibrosis,
inflammation, and macrophage infiltration. These contribute to insulin resistance and glucose intolerance in T2DM.
We employed a combination of in vitro and in vivo approaches to investigate the role of HIF1A in OSA and T2DM.
Cell and animal models were exposed to IH to simulate the hypoxic stress in OSA. The role of HIF1A was investigated
58
through treatment with PX-478, a known HIF1A inhibitor. IH exposure resulted in IL6-mediated inflammation in
adipocytes and macrophage co-culture that was reversed by pre-treatment with PX-478. Further, TallyHo mice
treated with PX-478 had markedly improved insulin sensitivity and glucose tolerance after IH challenge. These
metabolic improvements were associated with decreased AT fibrosis, inflammation and macrophage infiltration.
Trichrome stain indicated that collagen deposition was significantly reduced in AT of PX-478-treated TallyHo mice
exposed to IH. We also found that the inflammatory markers IL6, TNFa and MCP1 were decreased in AT of PX-478-
treated mice. Consistent with these, immunohistochemical staining confirmed lower frequency of macrophage
infiltration in the PX-478 group. Overall, we underscore the importance of HIF1A for the orchestration of pro-fibrotic
and pro-inflammatory changes of the AT in response to IH, serving as a crucial link between OSA and the
development of insulin resistance and glucose intolerance in T2DM.
Global Perspectives in Genomics and Medicine: An APSHG-HUGO Plenary Session
Precision Medicine: Making Sense of DNA Variants
Charles Lee (South Korea)

Director and Professor, The Jackson Laboratory for Genomic Medicine
Distinguished EWHA Professor, EWHA Womans University
President, Human Genome Organization
A major source of genetic variation in humans is single nucleotide polymorphisms (SNPs), that account for
0.1% of the human genome. The human genome also harbors hundreds of thousands of structural variants in the
form of DNA gains and losses (collectively termed copy number variants or CNVs) as well as balanced chromosomal
rearrangements such as insertions, inversions, and translocations. New technology and computational approaches
continue to be developed and utilized to accurately and comprehensively detect structural variants from next
generation sequencing data. Our latest data indicate that a genome that is sequenced to 30x coverage with Illumina
technology alone, will miss more than 100,000 indels and nearly 14,000 structural variants (>50 bp). These are
variants that would otherwise not be used in subsequent association studies nor incorporated into diagnostic assays.
Hence, we need to be more encompassing of new technologies and more computational methodologies to maximize
the usefulness of all genetic variants in personalized medicine.
59
Global Perspectives in Genomics and Medicine: An APSHG-HUGO Plenary Session
Oncogenomics: Closing the Cancer Gap
Edison Liu ( Singapore)

President and CEO
The Jackson Laboratory
Genetic mutations drive cancers and any one cancer can have a multitude of mutations. Therapeutic
decisions are guided by the presence of individual gene mutations in oncogenes (e.g. BCR-ABL, EML4-ALK, EGFR, and
BRAF) and even germline states as in BRCA mutations. The challenge now is to understand the interaction between
gene mutations in cancer. Specific combinations such as disruptive mutations in RB and TP53 are necessary to
achieve some transformed states, but with whole genome sequence data, we are observing genomic mutational
configurations that affect large regions of the genome which we call chromotypes: e.g. chromothripsis, and kataegis.
We describe a new cancer chromotype, the tandem duplicator phenotype (TDP) characterized by many single
tandem duplications distributed throughout the genome. Using the median tandem duplicon span size, we are able
to stratify the TDP into genomic subtypes that allowed for the identification of driver genes that induce this whole
genome effect: BRCA1, CCNE1, CDK12, all in combination with TP53 mutations. Finally, we show evidence for the
TDP to be associated with potential therapeutic response especially immune-oncology agents.
60
Plenary Session 4
Rare Are Common: How Rare Diseases Reveal Molecular Pathways for Common Disorders:
Inter-generational inheritance by SMCHD1
Shifeng Xue and Bruno Reversade (Singapore)
Institute of Molecular and Cell Biology of the Agency for Science, Technology and Research (A*STAR),
Singapore
Arhinia is an extremely rare syndrome characterized by the complete absence of the nose at birth. In
14 human cases studied, we identified de novo missense mutations in the epigenetic
regulator SMCHD1 that segregated with this striking condition (C. Gordon et al., 2017). Such findings are
in contrast to the SMCHD1 loss-of-function mutations that cause a late onset muscular dystrophy known
as FSHD2. Our biochemical tests and in vivo assays in Xenopus suggested that arhinia mutations behaved
as gain-of-function. On the contrary, N. Shawn et al., (2017) argued they were loss-of-function alleles based
on their observation that smchd1 zebrafish crispants displayed craniofacial anomalies. To resolve this
conundrum, we generated true maternal zygotic smchd1 knockout zebrafish. Although these did not
phenocopy any of the reported arhinia features, we uncovered an unsuspected maternal-only role
for smchd1 in the establishment of the vertebrate body plan via regulation of the HOX code. Together, our
results suggest that HOX epimutations brought about by the loss of SMCHD1 during oogenesis have long
lasting consequences into adulthood which cast a new light on the pathogenesis of Arhinia and FSHD2 in
humans.
61
Plenary Session 5
Precision Public Health for Infectious Diseases in Asia
Martin Hibberd (UK)

Professor, Emerging Infectious Diseases
London School of Hygiene and Tropical Medicine
Precision medicine is a concept that is rapidly gaining traction in recent years for diseases such as cancer,
as genomic advances couple together with specific diagnostics and therapies. However, infectious disease clinics
have already been doing precision medicine for many years, with diagnosis and treatment based on the genome of
the microbial agent. Today, infectious disease medicine is also starting to take advantage of the human genomics
developments and building a new, more prognostic, understanding of treatment options. For the tropical diseases
of Asia, this will require Asian research to ensure that these diseases are not left behind in providing new public
health benefits. This talk will highlight recent research in dengue, TB, leprosy, sepsis and respiratory infections that
are building towards the new era of precision health, integrating human genetics and human transcriptomic
responses towards prognostic applied therapies.
62
Day 3 Schedule
7:30AM-8:30AM iGNiTE Sessions: Genomic Networking and Training with the Experts (Skeletal dysplasias)
Rizal Ballroom A
David Sillence (Australia) and Maria Melanie Liberty B. Alcausin (Philippines)
8:30AM-9:15AM PLENARY SESSION 6
Chair: Brian Chung
Comprehensive application of multi-omic approaches for the genetic elucidation of "rare

diseases"
9:15AM-10:00AM PLENARY SESSION 7
Chair: Meow-Keong Thong
Gearing Up for the Phenomics Era

Li Jin (China)
POSTER SESSION 3
10:00AM-11:00AM COFFEE BREAK
VISIT TO EXHIBITS
11:00AM-11:45AM CLOSING PLENARY
Chair: Mercy Laurino
Clinical and Ethical Implications of CRISPR Therapies

Kelly E. Ormond (USA)
LUNCHEON SYMPOSIUM INDUSTRY SPONSORED: MEAD JOHNSON
12:00PM-1:00PM
Mary Anne D. Chiong (Philippines)
1:00PM-300PM CLOSING CEREMONIES
3:00PM-6:00PM TOUR OF INTRAMUROS: THE WALLED CITY (TICKETED EVENT)
63
Plenary Session 6
Comprehensive application of multi-omic approaches for the genetic elucidation of "rare diseases"
Co-Lead, Brain and Mitochondrial Research Group
Murdoch Children’s Research Institute
Co-Lead, Australian Genomics Health Alliance
Melbourne, Australia
To be most effective and timely, delivery of clinical genomic sequencing requires a team approach, with
collaboration between referring and specialist clinicians, genetic counsellors, laboratory scientists and
bioinformaticians. Delivery of genomic technologies at scale generates additional logistical, implementation and
ethical issues. To examine all of these issues we have established the Australian Genomics Health Alliance (AGHA)
(see: https://www.australiangenomics.org.au), a five-year health services research project aimed at accelerating
and evaluating the application of genomic testing into the Australian healthcare system. AGHA has four programs of
work: 1) development of national diagnostic and research networks to drive a coordinated and sustainable system
for genomic health care; 2) establishing standards and processes to capture and use genomic and clinical data as a
national approach for data federation and analysis; 3) building evidence for scalable, sustainable and equitable
genomic healthcare through evaluation, policy and ethics; 4) mapping workforce education and training needs for
effective delivery of genomic healthcare. Cutting across these for programs are 11 rare disease and 6 cancer
“flagships”, that are being used to test delivery of genomic testing into the clinics in real time. Clinical recruitment
and genomic testing are accessible through clinics in all of the Australian states and territories, with representation
and shared leadership across states. There is an emphasis on evaluation of outcomes as a part of the virtuous cycle
between research and clinical genomics practice. In this presentation an overview of the AGHA will be presented,
along with its programs, flagships and working group activities, and an overview will be provided of two of the rare
disease flagships, the mitochondrial flagship and the acute care flagship. Cases will be drawn from these two
flagships illustrating some of the challenges that have been encountered, highlighting some of the strategies that
were needed to confidently yield answers.
64
Plenary Session 7
Gearing Up for the Phenomics Era
Li Jin (China)
Vice President
Fudan University
Humankind faces an unprecedented assault of physical, environmental, biological and medical threats from
diverse interactive sources. In the last 40 years, the genomics had led the substantial progression of the life science.
However, the genetic paradigm has encountered the challenges due to the complexity of physiological and
pathological processes. To circumvent this barriers, researchers need to consider multiple dimensional phenotypes
and elucidate their intrinsic connections. To this end, phenomics has been presented as an approach that measure
and model of multiple omics parameters together with other biological metadata and their impact on disease risk at
the individual and population levels. Furthermore, phenomics may elucidate the gene-environment interactions that
underpin the differential risks, prevalence and emergent phenotypes of disease. International Human Phenome
Consortium (IHPC) of integrating world-wide centers had been proposed to establish with capacity and expertise in
large-scale human phenome investigation, and we hope that IHPC will lead a new wave of the discoveries in the life
sciences for improving the health of mankind.
65
Closing Plenary
Clinical and Ethical Implications of CRISPR Therapies
Kelly E. Ormond (USA)

Professor, Department of Genetics and Stanford Center for Biomedical Ethics
Stanford University
Gene editing has increased in feasibility and availability in the past 5 years. The scientific literature and
media include a lot of hype about potential uses and implications, including animals, agriculture and health areas.
Gene therapy and gene editing has a long history dating back to the 1980s, with the first examples of recombinant
DNA therapies, and of their oversight. After more than 30 years, gene therapies are finally being approved for clinical
use to treat human disease, and somatic gene editing clinical trials have also started. As they do, researchers and
participants are cognizant of the impact of the death of Jesse Gelsinger in early somatic gene therapy trials, which
set gene therapy trials back decades. Starting in 2015, reports of germline (embryo) gene editing began to be
published, starting with non-viable embryos and moving into viable embryos. A prestigious group of researchers,
including many who were involved in the first Asilomar conferences about recombinant DNA and some of the co-
discoverers of CRISPR technologies, called for a moratorium on germline gene editing. Between 2015 and 2018,
various policy making groups and professional organizations evaluated the issue and made statements, all of which
agreed that researchers should not proceed with pregnancies of gene edited embryos. Despite this, in November
2018, two twin girls were born after germline gene editing was performed on their CCRV5 genes. Since then, there
has been significant discussion in both media and the various policy making groups regarding how best to avoid
further episodes of germline gene editing. This talk will also review published work on attitudes of the public,
professionals and members of disease stakeholder groups towards gene editing.
66
B. PHOTO GALLERY
Registration
Opening Ceremonies
67
Exhibit Booths and Poster
Fellowship Night
Closing Ceremonies
68
Prepared by;
Cheryll Magbanaua-Calalo, MD
Secretariat
APCHG 2019
69

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13th Asia Pacific Conference on Human Genetics

“Advancing Translational Medicine and Collaborations in Genomics”

Day 1 November 7, 2019

8:30AM - 9:30AM OPENING CEREMONIES

2:00PM – 2:20PM A: Genomic Sequencing of Newborns

4:00PM-4:20PM A: Inherited Small Molecule Disorders: Current and Future Therapies

Mary-Claire King (USA)

Danilo A. Tagle (USA)

Mercy Y. Laurino (USA)

Breana Cham (Singapore)

Stephen Lam (Hong Kong)

Establishing a statewide genetic counselors’ association through an iterative process

Rifhan Azwani Mazlan

Carmencita D. Padilla (Philippines)

Veronica Wiley (Australia)

Yin-Hsiu Chien (Taiwan)

Gerard Pals1*, Winny Xie1

Bradford Therrell (USA)

Brian Chung (Hong Kong)

Juliana Lee (Malaysia)

Kathleen A. Leppig (USA)

Chen Ping (China)

Supachai Ekwattanakit (Thailand)

Suthat Fucharoen, Saovaros Svasti, Alisa Tubsuwan (Thailand)

Zilfalil Alwi (Malaysia)

Joy Y. Lee (Australia)

Meow-Keong Thong (Malaysia)

John Christodoulou (Australia)

Gerard Pals (Netherlands)

Common and Uncommon Symptoms , Diagnosis and Management Challenges in Pompe

Revisiting Current Consensus on the Diagnosis and Treatment of Pompe Disease

2:30PM-3:00PM Precision Medicine: Making Sense of DNA Variants

3:00PM-3:30PM Oncogenomics: Closing the Cancer Gap

Precision Public Health for Infectious Diseases in Asia

X-linked Dystonia-Parkinsonism (XDP) is an adult-onset neurodegenerative movement disorder that has so

Hans van Bokhoven (Netherlands)

Dung Vu Chi (Vietnam)

Ina Amarillo (USA)

Gender Assignment and Counseling for Disorders of Sexual Development

Gaucher disease (GD) is caused by a hereditary deficiency of glucocerebrosidase (GBA), resulting in

Global Perspectives in Genomics and Medicine: An APSHG-HUGO Plenary Session

Precision Medicine: Making Sense of DNA Variants

Charles Lee (South Korea)

Oncogenomics: Closing the Cancer Gap

Edison Liu ( Singapore)

Precision Public Health for Infectious Diseases in Asia

Martin Hibberd (UK)

Comprehensive application of multi-omic approaches for the genetic elucidation of "rare

Gearing Up for the Phenomics Era

Clinical and Ethical Implications of CRISPR Therapies

1:00PM-300PM CLOSING CEREMONIES

3:00PM-6:00PM TOUR OF INTRAMUROS: THE WALLED CITY (TICKETED EVENT)

Gearing Up for the Phenomics Era

Clinical and Ethical Implications of CRISPR Therapies

Kelly E. Ormond (USA)

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