Unit 3: Genetics

Some terminologies

Genetics: Genetics is a branch of biology concerned with the study of genes,

genetic variation, and heredity in organisms.
Chromosome: A chromosome is a nucleoprotein complex made of DNA and histone
proteins. In a broad sense chromosomes are the genetic material in eukaryotes.
A typical chromosome is consists of
a. Short arm
b. Centromere
c. Long arm
In all eukaryotes chromosomes occur in pairs. In humans we have 23 pairs of
chromosomes.
Homologous chromosomes: If two chromosomes have the same gene in the same
order along their chromosomal arms then they are called homologous chromosomes.
Humans have 23 pairs of chromosomes and the two members of each pair are
homologues of each other.
Gene:
Definition 1: An inherited factor that helps to determine a characteristic.
Definition 2:A segment of a DNA molecule that contains the information required
for the synthesis of a functional biological product, whether protein or RNA, is
referred to as a gene
Genes are found on the chromosome.
Allele: An allele is an alternate/variant form of a gene. A gene may have more than
one allele. Example T and t are the alleles for the gene that is responsible for
height in pea plants.
Alleles can be classified into various classes:
1. Dominant allele: In the view of Mendelian genetics an allele is dominant if it
expresses/has the same phenotypic effect in heterozygotes as well as in
homozygotes.
 2. Recessive allele: In the view of Mendelian genetics an allele is recessive if
it expresses only in homozygotes.
3. Null allele: Nonfunctional alleles are said to be null or amorphic. They are
almost always completely recessive.
4. Hypomorphic allele: Partially functional alleles are said to be hypomorphic.
They are recessive to alleles that are more functional, including (usually) the
wild-type allele.

Locus: Specific position on a chromosome that is occupied by an allele

Genotype: Set of alleles possessed by an individual organism. Depending on
genotype an individual can be :
1. Heterozygote/Heterozygous: An individual organism having two different
alleles of a particular gene.
2. Homozygote/Homozygous: An individual organism having two same alleles of
a particular gene.

Phenotype or trait: The appearance or manifestation of a character

Character or characteristic: An attribute or feature
Monohybrid cross: A monohybrid cross is a cross between two organisms with
different variations at one genetic locus of interest.
Dihybrid cross: Dihybrid cross is a cross between two individuals who differ in
two observed traits that are controlled by two distinct genes
True-breeding organism: Homozygous organism
Reproduction : It is the biological process by which new individual organisms
offspring are produced from their parents
Heredity: It is the passing on of traits from parents to their offspring through
reproduction (asexual or sexual)
Inheritance: It is the process by which genetic information is passed on from
parent to child
Self-pollination: The transfer of pollen from the anther to the stigma of the
same flower, or another flower on the same plant.
Cross-pollination: The transfer of pollen from one plant to the stigma of another
plant from the same species.
First Filial generation (F1): The first generation resulting from the initial cross
(mating) between the parental generation.
Second Filial generation (F2): The second generation resulting from the cross
between the F1 generation
Concept of homologous chromosomes:
Humans have 23 pairs of chromosomes and these are the genetic material which
passes on from one generation to another.

There are few important points in the above figure:

1. Both the figure contains 23 pairs of chromosomes

2. Each pair consists of 2 members (red color 3rd bracket) and they are known
as homologous chromosomes
3. Each pair of chromosomes are numbered numerically (1 to 22) except XX
and XY. They are the 23rd pair
4. The difference between male and female occurs due to the 23rd pair. In
males it is XY whereas in females it is XX. Rest of the chromosomes are
common for both of them
Structure of chromosome and concept of locus:
Let’s consider the chromosome pair number 1 and few details related to it :

1. There are 2 chromosomes and both of them are referred to as chromosome

1. These two chromosomes are homologous to each other
2. Each chromosome is consisting of a short arm, a centromere and a long arm
3. The black stripes on each arm of each chromosomes representing the
locus/position of a particular allele of a particular gene
4. Each locus numbered numerically and numbers are identical on both the
homologous chromosomes
5. The alleles are represented by english alphabet

Mendel’s law of inheritance

Gregor Mendel, through his work on pea plants, discovered the fundamental laws of
inheritance. He deduced that each gene comes in a pair (alleles) and are inherited
as distinct units, one from each parent. Mendel tracked the segregation of
parental genes and their appearance in the offspring as dominant or recessive
traits.
Note: At the time of mendel the existence of DNA and hence the concept
gene was not known. Mendel coined the term “factor” which is now known as
“gene”. So in his theory Mendel always mentioned the inheritance of factor(s).
For monohybrid cross one factor and for dihybrid cross two factors.

Mendel's Laws of Heredity/Inheritance are usually stated as:

1) Law of Dominance

In a heterozygote, one allele may suppress the presence of another.

In this case one allele dominates (also known as dominant allele) the other
(also known as recessive allele).

2) Law of Segregation

In a heterozygote, two different alleles segregate from each other during

the formation of gametes.
This law is based on the fact that the alleles do not show any blending and
that both the characters are recovered as such in the F2 generation though
one of these is not seen at the F1 stage.

3) The Law of Independent Assortment: The alleles of different genes

segregate, or as we sometimes say, assort, independently of each other.
Genes for different traits are sorted separately from one another so that
the inheritance of one trait is not dependent on the inheritance of another.

Before Mendel, other researchers had been working on several varieties of plants
by artificial pollination, but they failed to explain the mechanism of heredity. The
following were the two reasons behind their failure:

1. First, they considered simultaneously many characters in which parents

differed. This made the tracking the individual characters through
successive generations difficult
2. Second, they believed that the hereditary characters of parents (mother
and father) become thoroughly mixed in the offspring.
Mendel did realize the above two causes of his predecessor’s failure. In order to
overcome those difficulties he carefully planned experiments. Gregor Mendel,
conducted hybridisation experiments on garden peas for seven years (1856-1863)
and proposed the laws of inheritance in living organisms.

The reasons for Mendel’s success are:

1. Mendel chose garden pea plant for his experiments which was an annual,
naturally self-pollinating plant with several pairs of contrasting character
2. Mendel concentrated only on one character (a pair of traits) at a time.
3. He kept accurate records (both qualitative and quantitative).
4. He used statistical methods for analyzing the results.
5. The characters selected by Mendel were present on different chromosomes.
6. All the seven pairs of contrasting traits selected by him showed complete
dominance.

Table 1: Contrasting Traits Studied by Mendel in Pea

S.No. Characters Traits
1. Stem height Tall/dwarf
2. Flower colour Violet/white
3. Flower position Axial/terminal
4. Pod shape Inflated/constricted
5. Pod colour Green/yellow
6. Seed shape Round/wrinkled
7. Seed colour Yellow/green

Advantages of selecting pea plant

1. It is an annual plant and easy to grow. Because of its short life cycle, Mendel
was able to study several generations of the plant within a short period of
time
2. They show several pairs of visible characters with contrasting traits
 3. Its flowers are complete and predominantly self-pollinating.Because of
self-pollination, plants are homozygous. Therefore, pure lines of pea plant
were available
4. These plants are easy to control pollination artificially. Self pollination can
be prevented by removing anthers from the flowers. Thus cross–pollination
is also possible in this plant. The resultant offspring from such cross –
pollination is termed as Hybrid
5. Pea plants produced large number of seeds in one generation

Monohybrid cross : Experiment and Observations

For monohybrid cross, Mendel began with a pair of pea plants with two contrasting
traits, i.e., one tall (DD) and another dwarf (dd)
All the hybrid plants generated from the cross-pollination of tall (DD) and dwarf
(dd) plants were tall. Mendel called this as a first hybrid generation (F1)
He continued his experiment with self-pollination of F1 progeny plants.
Surprisingly, he observed that one out of four plants were dwarf while the other
three were tall. The tall and the short plants were in the ratio of 3:1 (phenotypic
ratio).
He also noted that no progeny was in intermediate height, i.e., no blending was
observed. He called them second hybrid generation and the offspring were called
Filial2 or F2 progeny

Genotypic ratio: 1:2:1

Phenotypic ratio: 3:1
Monohybrid cross : Conclusions

1. Based on these observations, Mendel proposed that something was being

stably passed down, unchanged, from parent to offspring through the
gametes, over successive generations. He called these things ‘factors’. Now
we call them genes.
2. Genes which code for a pair of contrasting traits are known as alleles. He
proposed that in a pair of dissimilar factors, one dominates the other (as in
the F 1 ) and hence is called the dominant factor while the other factor is
recessive (Law of Dominance)
3. Based on the F2 generation one can infer that during the process of meiosis,
the alleles of the parental pair separate or segregate from each other and
only one allele is transmitted to a gamete (Law of Segregation).

Dihybrid cross : Experiment and observations

For dihybrid cross, Mendel took a pair of contradicting traits together for
crossing, for example colour and the shape of seeds at a time.
He picked the wrinkled-green (ggww) seed and round-yellow (GGWW) seed and
crossed them. He obtained only round-yellow seeds in the F1 generation. This
indicated that the round shape and yellow colour of seeds are dominant in nature.
Then, F1 progeny was self-pollinated. This resulted in four different combinations
of seeds in the F2 generation. They were wrinkled-yellow, round-yellow,
wrinkled-green seeds and round-green in the phenotypic ratio of 9:3:3:1.

Dihybrid cross : Conclusion

Based upon such observations on dihybrid crosses (crosses between

plants differing in two traits) Mendel proposed a second set of generalisations
that we call Mendel’s Law of Independent Assortment. The law states that
‘when two pairs of traits are combined in a hybrid, segregation of one pair
of characters is independent of the other pair of characters’.
A small trick to group all the genotypes that are observed in the F2
generation in a dihybrid cross:

From the punnett square depicted above (table of genotypes in F2) one can
formulate a general formula to group all the genotypes in to four categories and
they are:

9/16 B_ T_ : Black and Tall

3/16 B_ tt : Black and short
3/16 bb T_ : White and Tall
1/16 bb tt : White and short
In the above example “B_” is the black space just after the B which means it can
be occupied by either “B” or “b”. Similarly “T_” the black space can be occupied by
“T” or “t”.

Concept of Test cross

By simply looking at the phenotype of a dominant trait (e..g, Tall), it is not possible
to know the genotypic composition. That is, for example, whether a tall plant from
F2 has TT or Tt composition, cannot be predicted. Therefore, to determine
the genotype of a tall plant at F2 , Mendel crossed the tall plant from F2
with a homozygous dwarf plant (tt). This he called a test cross.
There are two possible outcomes of a test cross:

Possibility 1: All tall at F1 after test cross:This signifies that the genotype of
the tall plant from the F2 is TT

Possibility 2: If 50% population is tall and 50% is short:This signifies that the
genotype of the tall plant from the F2 is Tt
Allelic Variation and Gene Function

Mendel identified two alleles, one dominant, the other recessive. This discovery
suggested a simple functional dichotomy between alleles, as if one allele did
nothing and the other did everything to determine the phenotype. However,
research early in the twentieth century demonstrated this to be an
oversimplification. Genes can exist in more than two allelic states, and each allele
can have a different effect on the phenotype.

Types of Dominance

Dominance can be understood in regard to how the phenotype of the heterozygote

relates to the phenotypes of the homozygote

1. Complete Dominance: This kind of dominance is observed from Mendel's

experiment. The idea that an individual organism possesses two different
alleles for a character (e.g., Height) but the trait (e.g., tall or dwarf)
encoded by only one of the alleles and is observed as phenotype. In the view
of Mendelian genetics an allele is dominant if it has the same phenotypic
effect in heterozygotes as in homozygotes—that is, the genotypes Aa and
AA are phenotypically indistinguishable.
2. Incomplete Dominance: Sometimes, a heterozygote has a phenotype
different from that of either of its associated homozygotes. Flower color in
the snapdragon, Antirrhinum majus, is an example. Pure-bred white
(recessive) and red (dominant) varieties when crossed, produce
heterozygotes that have pink flowers (F1 progeny). The allele for red color
(W ) is therefore said to be incompletely, or partially, dominant over the
allele for white color (w).
When a trait exhibits incomplete dominance, a cross between two
heterozygotes produces a 1 : 2 : 1 phenotypic ratio in the progeny instead of
3:1 ratio.
The most likely explanation is that the intensity of pigmentation in this
species depends on the amount of a product specified by the color gene.
Let's assume that the W and w alleles express red color pigment and no pigment
respectively. Then the WW homozygotes will have twice as much of the red
pigment as compared to the Ww heterozygotes and will therefore show deeper
color.
3. Codominance: In the case of codominance the heterozygote simultaneously
expresses the phenotypes of both parents. A good example is different types of
red blood cells that determine ABO blood grouping in human beings. ABO blood
groups are controlled by the gene I. The plasma membrane of the red blood cells
has sugar polymers that protrude from its surface and the kind of sugar is
controlled by the gene. The gene (I) has three alleles IA , IB and i. The alleles IA
and IB produce a slightly different form of the sugar while allele i does not
produce any sugar. Because humans are diploid organisms, each person possesses
any two of the three I gene alleles. IA and IB are completely dominant over i, in
other words when IA and i are present only IA expresses (because i does not
produce any sugar), and when IB and i are present IB expresses.
But when IA and IB are present together they both express their own types
of sugars: this is because of codominance. Hence red blood cells have both A and B
types of sugars. Since there are three different alleles, there are six different
combinations of these three alleles that are possible, and therefore, a total of six
different genotypes of the human ABO blood types.

Table 2: Table Showing the Genetic Basis of Blood Groups in Human Population
Multiple Alleles

The Mendelian concept that a gene exists in no more than two alleles, had to be
modified when a gene with three, four, or more alleles were discovered. For some
loci, more than two alleles are present within a group of organisms—the locus has
multiple alleles. (Multiple alleles may also be referred to as an allelic series.)
Although there may be more than two alleles present within a group of organisms,
the genotype of each individual diploid organism still consists of only two alleles.
The inheritance of characteristics encoded by multiple alleles is no different from
the inheritance of characteristics encoded by two alleles, except that a greater
variety of genotypes and phenotypes are possible.
A classic example of a gene with multiple alleles is the one that controls coat color
in rabbits or the blood group in humans.

Characteristics of dominance:
1. Dominance is a result of interactions between genes at the same locus; in
other words, dominance is allelic interaction.
2. Dominance does not alter the way in which the genes are inherited; it only
influences the way in which they are expressed as a phenotype.
3. The classification of dominance depends on the level at which the phenotype
is examined. As seen for cystic fibrosis, an allele may exhibit codominance at
one level and be recessive at another level.

Polygenic Inheritance

There are many characters which are generally controlled by three or more genes
and are thus called polygenic characters.

Polygenic inheritance is defined as inheritance of polygenic character. Besides

the involvement of multiple genes, polygenic inheritance also takes into account the
influence of the environment. Human skin colour is another classic example for this.
Gene Interaction: It is a part of polygenic inheritance and is a situation when the
expression of one gene is dependent on the other gene or genes. Law of
independent assortment is not applicable here.
Epistasis:
Epistasis is the phenomenon related to the gene interaction where one gene masks
(hides) the effect of another gene at a different locus.
The difference between dominance and epistasis is that in epistasis one gene
masks the effect of another gene at different locus. In epistasis, the gene that
does the masking is called an epistatic gene; the gene whose effect is masked
is a hypostatic gene. Epistatic genes may be recessive or dominant in their
effects.

There are few types of Epistasis:

1. Recessive epistasis

When the recessive allele of one gene masks the effects of the dominant allele of
the second gene.
Recessive epistasis is seen in the genes that determine coat color in Labrador
retrievers. These dogs may be black, brown, or yellow; their different coat colors
are determined by interactions between genes at two loci (although a number of
other loci also help to determine coat color). One locus determines the type of pig-
ment produced by the skin cells: a dominant allele B encodes black pigment,
whereas a recessive allele b encodes brown pigment. Alleles at a second locus
affect the deposition of the pigment in the shaft of the hair; dominant allele E
allows dark pigment (black or brown) to be deposited, whereas recessive
allele e prevents the deposition of dark pigment, causing the hair to be yellow. The
presence of genotype ee at the second locus therefore masks the expression of
the black and brown alleles at the first locus.
If we cross a black Labrador homozygous for the dominant alleles (BB EE) with a
yellow Labrador homozygous for the recessive alleles (bb ee) and then intercross
the F 1 , we obtain progeny in the F 2 in a 9 : 3 : 4 ratio:
Notice that yellow dogs can carry alleles for either black or brown pigment, but
these alleles are not expressed in their coat color. In this example of gene
interaction, allele e is epistatic to B and b, because e masks the expression of the
alleles for black and brown pigments, and alleles B and b are hypostatic to e. In
this case, e is a recessive epistatic allele, because two copies of e must be present
to mask the expression of the black and brown pigments.

2. Dominant epistasis

In dominant epistasis, only a single copy of an allele is required to inhibit the

expression of the allele at a different locus.
Dominant epistasis is seen in the interaction of two loci that determine fruit color
in summer squash, which is commonly found in one of three colors: yellow, white,
or green. When a homozygous plant that produces white squash is crossed with a
homozygous plant that produces green squash and the F 1 plants are crossed with
each other, the following results are obtained:

In the F 2 , 12/16 , or 3/4 , of the

plants produce white squash and
3/16 + 1/16 = 4/16 = 1/4 of the
plants produce squash having color. This outcome is the familiar 3: 1 ratio produced
by a cross between two heterozygotes, which suggests that
a dominant allele at one locus inhibits the production of pigment, resulting in white
progeny.
If we use the symbol W to represent the dominant allele that inhibits pigment
production, then genotype W_ inhibits pigment production and produces white
squash, whereas ww allows pigment and results in colored squash.
Among those ww F2 plants with pigmented fruit, we observe 3/16 yellow and 1/16
green (a 3 : 1 ratio). In this outcome, a second locus determines the type of
pigment produced in the squash, with yellow (Y_) dominant over green (yy). This
locus is expressed only in ww plants, which lack the dominant inhibitory allele W.
We can assign the genotype ww Y_ to plants that produce yellow squash and
the genotype ww yy to plants that produce green squash. The genotypes and their
associated phenotypes are:
W_ Y_ white squash
W_ yy white squash
ww Y_ yellow squash
ww yy green squash
Allele W is epistatic to Y and y: it suppresses the expression of these
pigment-producing genes. Allele W is a dominant epistatic allele because, in
contrast with e in Labrador retriever coat color and with h in the Bombay
phenotype, a single copy of the allele is sufficient to inhibit pigment production.

3. Duplicate recessive epistasis

In duplicate recessive epistasis two recessive alleles at either of two loci are
capable of suppressing a phenotype. This type of epistasis is illustrated by albinism
in snails. Albinism is the absence of pigment and is a common genetic trait in many
plants and animals.

Genetic Disorders: It is a disease or disorder that is caused by :

1. A mutation in one gene (monogenic/single gene disorder)
2. Mutations in multiple genes (multifactorial inheritance disorder)
3. Abnormalities in chromosome number (Chromosomal disorder)
Single gene disorder: Single gene disorders follow the Mendelian law of
inheritance and hence also known as Mendelian disorder. A single gene disorder can
be :

a. X-linked recessive
b. X-linked dominant
c. Y-linked
d. Autosomal recessive
e. Autosomal dominant

Inheritance of X-linked recessive disorder

Consider that the “h” allele is responsible for haemophilia (single gene disorder)
and it is X-linked recessive i.e, “h” allele is present on the X chromosome and it is
recessive in nature. The “H” allele is normal and also present on the X- chromosome
Situation 1: If Female is carrier and Male is Normal
In this case: 50% male will be
affected or normal and 50% female
will be carrier or normal. Less risk for
female and risk for male

Situation 2: If Female is affected and Male is Normal

In this case: 100% male will be affected

and 100% female will be the carrier.
Hence high risk for male children.

List of Single gene disorders in humans

Gene Mapping

Gene mapping describes the methods used to identify the locus of a gene and the
distances between genes
There are two distinctive types of "Maps" used in the field of genome mapping:
1. Genetic maps
2. Physical maps
While both maps are a collection of genetic markers (a gene or DNA sequence with
a known location on the chromosome) and gene loci genetic maps' distances are
based on the genetic linkage information, while physical maps use actual physical
distances usually measured in number of base pairs.