UNIT-I

CHARACTERISTICS & STRUCTURE OF GENES

Genetics is the branch of biology that deals with the study of hereditary & variations. Hereditary is the transmission of characters from parents to offspring. Mendel was the first to visualize a gene as the unit of inheritance in 1865. He called it as a FACTOR. The word GENE was introduced by JOHANNSON in 1909 for fundamental unit of heredity occupying a position in a chromosome. It was later found that the genes lay in a linear order in the chromosomes.

Thus, a GENE is a unit of inheritance which is carried from a parent by gamete in a chromosome & controls the expression of a specific character in a young one in cooperation with its alleles, other genes & environment.

But the modern concept of gene has greatly

changed from the factor in Mendel to unique sequences of nucleotide base pairs of modern geneticists. According to modern concept, A GENE is a segment of nucleic acid, usually a DNA has a unique sequence of nucleotide base pairs, codes for a specific polypeptide or rRNA or tRNA. DNA is a polymeric nucleic acid macromolecule composed of 3 types of subunits, i.e.; a 5C sugar (deoxyribose), a nitrogen containing base (Purine or Pyrimidine), & a Phosphate group.

In Human genome these polynucleotide chains are hundreds of millions of nucleotides long ranging from 50-250 million bp (base pairs) long. GENE can be defined as a segment of DNA molecule containing the code for amino acid sequence of a polypeptide chain & the regulatory sequences necessary for expression.

Thus, a definite relationship between the genes & proteins present in a cell. A change in the gene would change the code & give rise to different polypeptides. Vast majority of genes, interrupted by one or more noncoding genes called INTRONS. These are initially transcribed into RNA in the nucleus but are not present in the mature mRNA in the cytoplasm. Introns alternate with the coding sequences, EXONS, which ultimately codes for the amino acid sequences of proteins

A GENE includes1) Not only the actual coding sequences but also adjacent nucleotide sequences required for the proper expression of the gene i.e; for the production of mRNA. 2) The adjacent nucleotide sequences provide the initiation & termination signals for the synthesis of mRNA. 3) At the 5 end lies promoter genes, which are DNA sequences where RNA polymerases binds for the transcription of RNA by structural genes. Here the initiation occurs.

4) Regulatory genes that codes for repressor proteins for regulating the transcription. These are Enhancers, Silencers, & Locus controlling regions. 5) At the 3 end of the gene lies an untranslated region of importance that contains signal in addition of a sequence of adenosine residues (Poly-A tail) to the end of mature mRNA. Besides this the terminator gene can also be there which are DNA regions where RNA polymerases activity stops to suspend transcription of structural gene.

CHROMOSOMES (Gk. Chroma-colour, soma-body) are thread like or rod like DNA protein hereditary structures which stores replicates & transmits coded information of biological importance. In several organisms the sex of an individual is determined by specific Chromosomes called Sex. Sex is an aggregate of those morphological, physiological & behavioral qualities that differentiates the organisms. Egg producing individuals are called Females (22+2X) & Sperms producing individuals as Males (22+XY).

 Hofemister Firstly seen them W. Waldeyer coined the term CHROMOSOMES

Sutton & Boveri Chromosomal theory of

inheritance
Ultimately ,it has been said that Chromosomes

are the physical basis of life while the DNA as the chemical basis of life.

SIZE:
Length is 0.5-32 micrometer

Breadth is 0.2-3 micrometer

SHAPE
Different in every phase like elongated thread

like structure in interphase , Condensed to

assume rod shaped in Late prophase &

metaphase.

 On the basis of location of centromere,

chromosomes can be

1. Metacentric
2. Submetacentric 3. Acrocentric

4. Telocentric

Chromosomes consists of :

1. Pellicle 2. Matrix 3. Centromere 4. Chromomere

5. Chromonemata
6. Primary constriction 7. Secondary constriction & 8. Telomeres.

FUNCTIONS
1. Contains genes 2. Controls synthesis of structural proteins, helps

in cell division, & growth

3. Synthesizes particular enzymes 4. Controls cell metabolism 5.

Replicate themselves

6. Determines the sex of an individual 7. Introduces variation 8. Link between Parents & offspring.

DNA

a) b) c)

Genes are encoded in the DNA that makes up a number of rod shaped organelles called chromosomes. DNA is the key molecule of the living world . DNA is a polymeric nucleic acid macromolecule composed of three types of subunits; A 5-C sugar(Deoxyribose) A nitrogen containing base (Purine & Pyramidine) A phosphste group.

 It is the

largest macromolecule with a

molecular weight of 108 -1011 with the exception of some viruses.

It is the hereditary material of all organisms.
DNA is long double chained polymer of several

thousands dexyribonucleotides placed end to end in two rows held together by hydrogen

bonding.

 Bond linking an individual sugar residue to

the neighbouring sugar residues is a 3,5 phosphodiester bond.

DNA is a double helical structure in which

2 DNA strands are held together by weak

hydrogen bonding to form a DNA duplex.

Hydrogen bonding occurs between laterally

opposed bases, base pairs , of two strands of the DNA duplex according to Watson & Crick.

 The two spiral strands of DNA are called DNA

duplex. These are not coiled upon each other but the double strand is coiled upon itself around a common axis like a rope stair case with the solid steps twisted into a spiral .
Due to spiral twisting two strands are

interwined in a clockwise direction i.e; in a right hand helix, & run in opposite direction.
The DNA duplex comes to have 2 types of

alternative grooves, Major & Minor

One turn of spiral has 10 nt. On each strand

of DNA.

 Each nucleotide occupies 3.4 .

& completes turn in 34

Diameter of the DNA molecule is 20 .

DNA is a polymeric nucleic acid

macromolecule composed of three types of subunits;

a)A 5-C sugar (Deoxyribose) b)A nitrogen containing base (Purine &

Pyramidine)
c)A phosphate group.

DEOXYRIBOSE
A pentose sugar Consists of 5C atoms plus a single atom of

oxygen.
The fifth carbon is outside the ring & is the

part of CH2 group.

The four atoms of the ring are numbered 1,2

,3 & 4.
The carbon of CH2 is numbered 5.
There are 3-OH groups in position numbered

1, 3, 5 .

NITROGENOUS BASES
Organic ring compounds 2 types:

Purines &
Pyramidines Purines: Are 9 membered double rings with nitrogen at 1, 3, 7 & 9.Includes Adenine & Guanine. Pyramidines: Single ringed compounds with nitrogen at position 1& 3 of a six membered ring. Includes cytosine & Thyamine.

PHOSPHATE
Each phosphate group is joined to carbon

atom 3 of one Deoxyribose & to carbon atom

5 of the another. The two ends are oriented

in opposite directions. The 3 end of one

strand corresponds to the 5 end of the other.

 Allows the transmission of the clinical

information from one cell to its daughter cells.

Helps in Replication & Synthesizes new complementary strands.

Sex Determination is a mechanism which takes part in establishing the sex of an individual. Sex determination is of 3 types: 1.Progamic Before fertilization as due to cytoplasm of the egg. 2.Syngamic At the time of fertilization. 3.Epigamic - After fertilization during development.

From the cytological studies on insects, it became clear that there were constant differences in the chromosomal content of males & females. In one species; sex was seen to have a chromosome which lacked a pairing partner. This is referred to as XO pair. In other species ; both the sexes had same chromosome, but the cells of one of the sex contained a chromosome pair which was unequal in size & shape.

From the above observations, it is clear that Sexes with heteromorphic pairs are heterogametic, with one X & one Y chromosome as in males & Human Females are homogametic with two X chromosomes in somatic cells. Sex of an organism depends upon the combination of sex chromosomes it received from the parents & would thus be determined by type of gamete denoted by heterogametic parent.

It has been found by Barr that Interphase nuclei of Human females possess small distinct chromatin body called Sex Chromatin, Barr Body or X-Chromatin. Barr body is produced from the partial inactivation of one X-chromosome & development of faculatative heterochromatin in it. Any of the two X-chromosome can become heterochromatic. It begins in the late blastocyst stage with the germ cells developing inactivation towards the last.

The X-chromosome is reactivated in meiotic prophase. The small arm of the heterochromatic X-chromosome continue to bear active genes throughout. In the rest of the body,it is random either paternal or maternal.,so named as RANDOM INACTIVATION. Dosage Compensation is the other phenomenon which is achieved through the Random Inactivation. The term is used for the mechanism that lead to the same amount of expression for X-linked genes in females as in males.

X-INACTIVATION

Number of Barr bodies is one less than the no. of Xchromosomes present in an individual. For E.g. One for normal XY, two for XXX & no Barr body for XO. These facts lead to LYONs HYPOTHESIS lead by MARY LYON. The heterochromatic X-chromosome is inactive in terms of gene expression. Inactivation which occurs during embryogenesis is random. Inactivation is permanent i e; once an X-chromosome is has been inactivated in a given cell; the same chromosome will be inactive in all the somatic cells.

PATTERNS OF INHERITANCE

MENDELIAN THEORY OF INHERITANCE

 In humans, 11,000 traits or disorders

exhibit single gene unifactorial or Mendelian inheritance. Characters such as: Height & many common familial disorders such as Diabetes, Hypertension etc. do not follow a single pattern of inheritance. Autosomal: A trait or disorder which is determined by a gene on the autosomes. Sex-Linked: A trait or disorder which is determined by a gene on one of the

AUTOSOMAL DOMINANT INHERITANCE

It is one which manifests in heterozygous

state i.e. in a person possessing both an abnormal or mutant allele & normal allele. Features are1. Male & Female affected in equal proportions. 2. Affected individual in multiple generations. 3. Transmissions by individual of both sexes i.e. male to male, male to female, female to male, female to female. This pattern of inheritance is also called

MULTIPLE ALLELES & BLOOD GROUPS

An allele is one member of a pair or series of

different forms of a gene. Usually alleles are coding sequences, but sometimes the term is used to refer to a non-coding sequence. For example, in Mendel's pea investigations, he found that there was a gene that determined the color of the pea pod. One form of it (one allele) creates yellow pods, & the other form (allele) creates green pods. When the gene for one trait exists as only two alleles & the alleles play according to Mendel's Law of Dominance, there are 3 possible genotypes (combination of alleles) & 2 possible phenotypes (the dominant one or the recessive one).

 Using the pea pod trait as an example, the

possibilities are like so:

GENOTYPES RESULTINGPHENOTYPE Homozygous Dominant (YY) Heterozygous (Yy) Homozygous Recessive (yy)

Yellow Yellow Green

where Y = the dominant allele for yellow & y = the recessive allele for green

 If there are only two alleles involved

in determining the phenotype of a certain trait, but there are three possible phenotypes, then the inheritance of the trait illustrates either incomplete dominance or codominance. In these situations a heterozygous (hybrid) genotype produces a 3rd phenotype that is either a blend of the other two phenotypes (incomplete dominance) or a mixing of the other phenotypes with both appearing at the same time (codominance).

 Here's an example with Incomplete

Dominance:

GENOTYPES RESULTINGPHENOTYPE BB = Homozygous Black Fur BW = Heterozygous WW = Homozygous White White Fur where B = allele for black & W = allele for white

Black Grey Fur

 And here's an example with Codominance:

GENOTYPES PHENOTYPE BB = Homozygous Black BW = Heterozygous WW = Homozygous White

RESULTING Black Fur Black & White Fur White Fur

where B = allele for black & W = allele for white

 If there are 4 or more possible phenotypes

for a particular trait, then more than 2 alleles for that trait must exist in the population. We call this "MULTIPLE ALLELES". One such gene which is of great interest to humans is the ABO blood group gene. This particular gene has three alleles, rather than two. Of course, each of us has only two sets of chromosomes, so any one individual has only two of these alleles at once. But the presence of three different alleles means that there are six possible genotypes, rather than the three possible for the more familiar two-allele situation.

 For the ABO gene, the three

alleles are the IA, IB and i alleles. We typically call these alleles "A," "B," and "O," but of course our rules for assigning symbols to alleles demand that all three be represented by some version of the same symbol. In this case, that common symbol is the letter "I," which stands for "immunoglobin."

 As the symbols above should suggest, the i

allele (the "O" allele) is recessive to both the IA and IB alleles (the "A" and "B" alleles). The IA and IB show co-dominance. This means that in an individual who is heterozygous for these two alleles, the phenotypes of both alleles are completely expressed, thus producing blood type AB. Thus we have the following: Genotype Phenotype ii Type O IAIA or IAi Type A IBIB or IBi Type B IAIB Type

 The other aspect of blood type

which is of most interest to us is the Rh factor. Genetically, this is much simpler than the ABO system. It has only two alleles, one dominant (Rhpositive) and one recessive (Rh-negative). However, this facet of our blood type has some serious implications when we reproduce

SEX-LINKED INHERITANCE
It refers to the pattern of

inheritance shown by genes which are located on either of the sexchromosomes. Genes carried on X-chromosomes are referred to as X-linked while genes on Y-chromosomes are called Y-linked & accordingly Dominant & Recessive

INHERITNCE
These are the disorders which are

manifest in heterozygous females as well as in males who has mutant allele on his single X-chromosome. Features are:
Males & females are affected but often with

an excess of females. Females are less severely affected than males. Affected males can transmit the disorder to their daughters not to their sons.

 Dig.6.15 Pedigree of X-linked dominant trait.

 For e.g. Vitamin-D resistant

rickets, which can be due to deficiency of Vitamin-D, but in Vitamin-D resistant rickets disorder, occurs when there is an adequate dietary intake of vitamin-D. In X-linked dominant form of Vitamin-D resistant rickets, both males & females are equally affected but females usually have less severe skeletal changes than males.

INHERITNCE
Determined by a gene carried on the X-

chromosome & usually only manifests in males. A male with a mutant allele on his single X-chromosome is said to be hemizygous for that allele. Diseases inherited in an X-linked manner are transmitted by healthy female carriers to affected males, as well as by affected males to their obligate carried daughters with a consequent risk to male grandchildren through these disorders. This type of pedigree is sometimes referred as Diagonal pattern of inheritance.

Carrier females Xh X Carrier males

X XhX XX Y XhY XY

In humans, several X-linked disorders are known in which heterozygous females have a mosaic phenotype with a mixture of features of the normal & mutant alleles. For E.g. in Xlinked ocular albinism the iris & ocular fundus of affected males are completely lacking in pigment. & in females heterozygous for ocular albinism reveals a mosaic pattern of pigmentation, which can be explained through X-inactivation. In the pigmented area the normal gene is on the active X chromosome while in depigmented area the mutant allele is on the active Xchromosome.

Y-LINKED INHERITNCE
Y-LINKED OR HOLANDRIC INHERITANCE shows that

only males are affected. Males are affected only. An affected male transmits it disorder to all his sons but none of his daughter. For e.g. Hairy ears & porcupine skin. It has been found that this type of inheritance is due to the H-Y histocompatibility antigen & genes involved in spermatogenesis are carried on the Y-chromosome & therefore manifests holandric inheritance. The latter if deleted leads to infertility.

MECHANISM OF INHERITANCE
Genetics is the study of the ways in

which the characters of an organism are inherited by its offspring. A number of plants and animals have been studied intensively by geneticists because they have simplified mechanisms that lend themselves to scientific investigation and analysis.

 The basic units of heredity are

called genes and these are carried in the chromosomes. Like the chromosomes these genes are in pairs, one inherited from the father and one from the mother. In the simplest possible situation a single character is controlled by one such pair of genes.

 The actual situation is often more

complicated because one gene pair may control several characters or alternatively several gene pairs may affect a single character. If the two genes of a pair are of similar type the animal is described as homozygous or a homozygote. Alternatively if the two genes of a pair are dissimilar then it is heterozygous and the animal is described as a heterozygote.

 Knowledge of the character and

behaviour of the genes is of vital importance in understanding the genetic process. The two genes in a pair do not fuse or mix even when they are dissimilar in character. They retain their integrity and when reproductive cells are produced they can separate again. The separation of every pair of genes into different reproductive cells is termed segregation.

 These basic principles of

inheritance may be referred to as 'Mendelian' after Father Gregor Mendel, who investigated the patterns of simple inheritance and first proposed the existence of inheritance factors.

 The Mendelian principle can be

illustrated by the case of the oriental swallowtail butterfly Papilio memnon. The female is polymorphicand these different forms are determined genetically. The butterflies are tailed in the form achates and tail-less in the form agenor. The tail-less butterflies are homozygous (ie have two tail-less genes) while the tailed butterflies may be homozygous (two tailed genes) or heterozygous (one tailed gene and one tail-less gene).

 It is the usual situation for

one gene type in a pair to be dominant, suppressing the other member of the pair when they occur together in the heterozygous condition. In this species the tailed gene is dominant while the tail-less gene is recessive.

 It should be emphasized, however,

that the recessive gene still retains its genetic potential for future generations, but it will not be expressed in the appearance of the butterfly unless it is paired with a second tail-less gene. This important point is underlined by the use of the terms 'genotype' for the genetic make-up of an individual and 'phenotype' for its actual appearance

 The fate of the genes is traced through to

the next generation in the following diagram T represents the dominant tailed gene (achates) while represents the recessive tail-less gene (agenor). In the diagram parents are both homozygous. Because T is dominant over t, it will be seen that the first generation females are all tailed in appearance, while carrying both genes. It should be remembered that the male parent may carry the genetic constitution for achates or agenor but does not show either of these forms since they are exclusively female forms.

 If a tailed F1 female of this brood

is paired with one of her brothers the resulting F2 females will be tailed and tail-less in the ratio 3 : 1 respectively, as in the bottom diagram. Three of the second generation have the dominant T gene, so have tails; one has no T factor (only the t gene) so has no tail.

 In practice this ratio may not be

exactly achieved since some of these characters will be inherited by males and will not therefore be expressed in the F2 generation. This system of two alternatives, a character being either present or absent, is much more common than situations where 'mixing' occurs to give intermediate types between the parental forms.