CHAPTER 4 - PRINCIPLES OF INHERITANCE AND VARIATION

Principles of Inheritance and Variation

Principles of Inheritance and Variation deals with the study of inheritance and variation through genetics.

Genetics

Genetics is the branch of biology which deals with study of inheritance and variation of characters from parents to offspring. Term 'genetics' was given by W. Bateson (Father of Modern Genetics).

Inheritance

Inheritance is the process by which characters are passed on from parent to progeny.

Variation

Variation is the degree of characters by which progeny differ from their parents, siblings. It may be natural and artificial.

Mendel’s Laws of Inheritance

Gregor Mendel, conducted hybridisation experiments on garden peas for seven years (1856-1863)
He proposed the laws of inheritance in living organisms.
He conducted cross pollination experiments using several true-breeding pea lines.
He selected 14 true-breeding pea plant varieties, as pairs which were similar except for one character with contrasting traits.

Contrasting Traits Studied by Mendel in Pea

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

Contrasting Traits Studied by Mendel in Pea

His laws based on inheritance of genes.
1. Inheritance of one gene - Here are two laws -
  1. Law of Dominance
  2. Law of Segregation
2. Inheritance of two genes - Here is one law -
  1. Law of Independent Assortment

Inheritance of One Gene

In hybridisation experiment, Mendel crossed tall and dwarf pea plants to study the inheritance of one gene.
He collected the seeds produced as a result of this cross and grew them to generate plants of the first hybrid generation.
- This generation is also called the Filial₁ progeny or the F₁.
He observed that all the F₁ progeny plants were tall, like one of its parents; none were dwarf.
He made similar observations for the other pairs of traits – he found that the F₁ always resembled either one of the parents, and that the trait of the other parent was not seen in them.
Mendel then self-pollinated the tall F₁ plants and to his surprise found that in the Filial generation some of the offspring were ‘dwarf ’; the character that was not seen in the F₁ generation was now expressed.
The proportion of plants that were dwarf were 1/4th of the F₂ plants while 3/4th of the F₂ plants were tall.
The tall and dwarf traits were identical to their parental type and did not show any blending, that is all the offspring were either tall or dwarf, none were of in-between height.
Similar results were obtained with the other traits.
Results - Only one of the parental traits was expressed in the F₁ generation while at the F2 stage both the traits were expressed in the proportion 3:1. The contrasting traits did not show any blending at either F₁ or F₂ stage.

Genes

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 as ‘factors’. Now we use term 'genes' for factors.
Genes - Genes are the units of inheritance. They contain the information that is required to express a particular trait in an organism.

Alleles

Location of genes on chromosomes which code for a pair of contrasting traits are known as alleles, i.e., they are slightly different forms of the same gene.
They may be homozygous or heterozygous.

Alphabetical Symbols For Each Gene

The capital letter is used for the trait expressed at the F1 stage and the small alphabet for the other trait.
e.g. character of height
- T is used for the Tall trait and t is for the ‘dwarf’, and T and t are alleles to each other.
- Hence, in plants the pair of alleles for height would be TT, Tt or tt.
It is convenient and logical to use the capital and lower case of an alphabetical symbol to remember this concept of dominance and recessiveness.

Homozygous

The identical allelic pair of genes for a character at a same locus (location) is homozygous.
- e.g. For pure tall plant, allelic pair of genes 'TT' are homozygous.
  - For pure dwarf plant, allelic pair of genes 'tt' are homozygous.

Heterozygous

The non-identical and contrasting allelic pair of genes for a character at a same locus (location) is heterozygous
- e.g. For hybrid tall plant, allelic pair of genes 'Tt' are heterozygous.

Genotype

The factors (or gene) on chromosomes regulating the characters are called the genotype.
- e.g. the pair of alleles for height are TT, Tt or tt.

Phenotype

The physical expression of the chraracters is called phenotype.
- e.g. the pair of alleles for tall plant are TT, Tt. Tallness is phenotype of this genotype.

Dominant

The character which expresses itself in F₁ generation is called dominant character.

Recessive

The character which does not express itself in F₁ generation but expresses itself F₂ generation is called recessive character.

Monohybrid Cross

The cross between pure homozygous dominant and recessive plant to study the inheritance of one gene is termed as monohybrid cross.
It can easily be understood by Punette Square.

Punette Square

It was developed by a British geneticist, Reginald C. Punnett.
It is a graphical representation to calculate the probability of all possible genotypes of offspring in a genetic cross.
The possible gametes are written on two sides, usually the top row and left columns.
All possible combinations are represented in boxes below in the squares, which generates a square output form.

Test Cross

In a typical test cross an organism showing a dominant phenotype (and whose genotype is to be determined) is crossed with the recessive parent instead of self-crossing.
The progenies of such a cross can easily be analysed to predict the genotype of the test organism.

Law of Dominance

Characters are controlled by discrete units called factors which occur in pairs.
In a dissimilar pair of factors, one factor of the pair dominates (dominant) the other (recessive).
The law of dominance explains the expression of only one of the parental characters in a monohybrid cross in the F1 and the expression of both characters in the F2.
It also explains the proportion of 3:1 obtained at the F2.

Law of Segregation

The parents contain two alleles which segregate from each other during gamete formation, each gamete receives only one of the two factors. This is called law of segregation.

Incomplete Dominance

In a monohybrid cross, when none of the characters of the parent appears at F₁, but intermediate character appears i.e. no charater dominates. This is called incomplete dominance.
Both characters appear as an intermediates.

Co-dominance

In this, both of the characters of the allelic pair appear simultaneously at F₁.
In this, both characters express themselves simultaneously.
There are more than two, i.e., three alleles, governing the same character.
e.g. ABO blood group

Inheritance of Two Gene

Mendel crossed pea plants to study the inheritance of two gene i.e. shape and color of seeds.
This is also called dihybrid cross.

Dihybrid Cross

The cross between pure homozygous dominant and recessive plant to study the inheritance of two gene is termed as dihybrid cross.
This can also be understood by Punette Square.
This leads to law of independent assortment.

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’.
The ratio of 9:3:3:1 can be derived as a combination series.

Chromosomal Theory of Inheritance

Walter Sutton and Theodore Boveri noted that the behaviour of chromosomes was parallel to the behaviour of genes and used chromosome movement to explain Mendel’s laws.
Chromosomes as well as genes occur in pairs.
The two alleles of a gene pair are located on homologous sites on homologous chromosomes.
Sutton and Boveri argued that the pairing and separation of a pair of chromosomes would lead to the segregation of a pair of factors they carried.
Sutton united the knowledge of chromosomal segregation with Mendelian principles and called it the chromosomal theory of inheritance.

Linkage and Recombination

Morgan carried out several dihybrid crosses in Drosophila to study genes that were sex-linked.
He hybridised yellow-bodied, white-eyed females to brown-bodied, red-eyed males and intercrossed their F1 progeny.
The two genes were located on the same X chromosome.
He observed that the two genes did not segregate independently of each other.
He did not found F₂ progeny in ratio of 9:3:3:1 (expected when the two genes are independent).
- i.e F₂ ratio deviated very significantly from the 9:3:3:1 ratio.
He concluded that when the two genes in a dihybrid cross were situated on the same chromosome, the proportion of parental gene combinations were much higher than the non-parental type.
Linkage -
- The physical association of the two genes on a chromosome of parental type is termed as linkage.
Recombination -
- The physical association of the two genes on a chromosome of non-parental type is termed as recombination.
Morgan and his group also found that even when genes were grouped on the same chromosome,
- some genes were very tightly linked (showed very low recombination)
- while others were loosely linked (showed higher recombination).
His student Alfred Sturtevant used the frequency of recombination between gene pairs on the same chromosome as a measure of the distance between genes and ‘mapped’ their position on the chromosome.

Polygenic Inheritance

Those traits are generally controlled by three or more genes are called as polygenic traits.
Inheritance of multiple genes are termed as polygenic inheritance.
Polygenic inheritance also takes into account the influence of environment besides the involvement of multiple genes.
e.g. Human skin colour

Pleiotropy

When a single gene can exhibit multiple phenotypic expression, such a gene is called a pleiotropic gene.
e.g. Disease phenylketonuria, which occurs in humans.
- The disease is caused by mutation in the gene that codes for the enzyme phenyl alanine hydroxylase (single gene mutation).
- This manifests itself through phenotypic expression characterised by mental retardation and a reduction in hair and skin pigmentation.

Sex Determination

History of Sex Determination

The cytological observations made in a number of insects led to the development of the concept of genetic/chromosomal basis of sex-determination.
Henking (1891) could trace a specific nuclear structure in 50% of sperms.
He gave a name to this structure as the X body but he could not explain its significance.
The ‘X body’ of Henking was in fact a chromosome and that is why it was given the name X-chromosome.
Due to the involvement of the X-chromosome in the determination of sex, it was termed as sex chromosome, and the rest of the chromosomes were named as autosomes.

Male Heterogamety

There are two types of sex determining mechanisms -
- XO type - gametes produced by male either with or without X-chromosome
- XY type - gametes produced by male either with X-chromosome or with Y-chromosome
Such types of sex determination mechanism is male heterogamety.

Female Heterogamety

In birds, there are different types of sex determining mechanisms -
- ZW type - gametes produced by female with Z-chromosome or with W-chromosome
Such types of sex determination mechanism is female heterogamety.

Sex Determination in Humans

Sex determining mechanism in humans is XY type.
There are 22 pairs autosomes and one pair sex chromosome.
During spermatogenesis among males, two types of gametes are produced. 50 per cent of the total sperm produced carry the X-chromosome and the rest 50 per cent has Y-chromosome besides the autosomes.
Females produce only one type of ovum with an X-chromosome.
There is an equal probability of fertilisation of the ovum with the sperm carrying either X or Y chromosome.
In case the ovum fertilises with a sperm carrying X-chromosome the zygote develops into a female (XX) and the fertilisation of ovum with Y-chromosome carrying sperm results into a male offspring.
Thus, it is evident that it is the genetic makeup of the sperm that determines the sex of the child.
It is also evident that in each pregnancy there is always 50 % probability of either a male or a female child.
It is unfortunate that in our society women are blamed for giving birth to female children and have been ostracised and ill-treated because of this false notion.

Sex Determination in Honey Bee

The sex determination in honey bee is based on the number of sets of chromosomes an individual receives.
An offspring formed from the union of a sperm and an egg develops as a female (queen or worker), and an unfertilised egg develops as a male (drone) by means of parthenogenesis.
This means that the males have half the number of chromosomes than that of a female.
The females are diploid having 32 chromosomes and males are haploid, i.e., having 16 chromosomes.
This is called as haplodiploid sex-determination system.
This system has special characteristic features such as the males produce sperms by mitosis, they do not have father and thus cannot have sons, but have a grandfather and can have grandsons.

Mutation

Mutation is a phenomenon which results in alteration of DNA sequences and consequently results in changes in the genotype and the phenotype of an organism.
Mutation is also a phenomenon that leads to variation in DNA.
Point mutation -
- It is the insertion or deletion of a single base pair in structural gene or DNA.
- e.g. sickle cell anemia
Frameshift mutation -
- Insertion or deletion of one or two bases changes the reading frame from the point of insertion or deletion.
Mutagens -
- Many chemical and physical factors that induce mutations are referred as mutagens.
- e.g. UV radiations

Genetic Disorder

The tool to study genetic disorder is pedigree analysis.
Genetic disorders may be grouped into two categories –
- Mendelian disorders and
- Chromosomal disorders.

Pedigree Analysis

An analysis of study of the family history about inheritance of a particular trait providing an alternative in a several of generations of a family is called the pedigree analysis.
In human genetics, pedigree study provides a strong tool, which is utilised to trace the inheritance of a specific trait, abnormality or disease.
A number of disorders in human beings have been found to be associated with the inheritance of changed or altered genes or chromosomes.

Mendelian disorders

Mendelian disorders are mainly determined by alteration or mutation in the single gene.
These disorders are transmitted to the offspring on the same lines.
The pattern of inheritance of such Mendelian disorders can be traced in a family by the pedigree analysis.
Most common and prevalent Mendelian disorders are
- Haemophilia
- Cystic fibrosis
- Sickle-cell anaemia
- Colour blindness
- Phenylketonuria
- Thalassemia
- Myotonic dystrophy
- Muscular dystrophy
- Skeletal dysplasia etc.
It may be dominant or recessive, X-linked recessive.

Colour blindness

It is a sex-linked recessive disorder.
Reason -
- This is due to defect in either red or green cone of eye resulting in failure to discriminate between red and green colour.
- This defect is due to mutation in certain genes present in the X chromosome.
It occurs in about 8 per cent of males and only about 0.4 per cent of females.
- This is because the genes that lead to red-green colour blindness are on the X chromosome.
- Males have only one X chromosome and females have two.
The son of a woman who carries the gene has a 50% chance of being colour blind.
- The mother is not herself colour blind because the gene is recessive.
- That means that its effect is suppressed by her matching dominant normal gene.
A daughter will not normally be colour blind, unless her mother is a carrier and her father is colour blind.

Haemophilia

This is a sex-linked recessive disorder.
This shows its transmission from unaffected carrier female to some of the male progeny.
In this disease, clotting of blood is affected which results in non-stop bleeding.
The heterozygous female (carrier) for haemophilia may transmit the disease to sons.
The possibility of a daughter becoming a haemophilic is extremely rare because unless her mother is a carrier and her father is haemophilic.
The family pedigree of Queen Victoria shows a number of haemophilic descendents as she was a carrier of the disease.

Sickle-cell anaemia

This is an autosome linked recessive.
The disease is controlled by a single pair of allele, Hb^A and Hb^S.
Out of the three possible genotypes only homozygous individuals for Hb^S (Hb^SHb^S) show the diseased phenotype.
Heterozygous (Hb^AHb^S) individuals appear apparently unaffected but they are carrier of the disease as there is 50 per cent probability of transmission of the mutant gene to the progeny, thus exhibiting sickle-cell trait.
The defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the beta globin chain of the haemoglobin molecule.
The substitution of amino acid in the globin protein results due to the single base substitution at the sixth codon of the beta globin gene from GAG to GUG.
The mutant haemoglobin molecule undergoes polymerisation under low oxygen tension causing the change in the shape of the RBC from biconcave disc to elongated sickle like structure.

Phenylketonuria

This is an autosomal recessive trait.
The affected individual lacks an enzyme that converts the amino acid phenylalanine into tyrosine.
As a result of this phenylalanine is accumulated and converted into phenylpyruvic acid and other derivatives.
Accumulation of these in brain results in mental retardation.
These are also excreted through urine because of its poor absorption by kidney.

Thalassemia

This is also an autosome-linked recessive blood disease.
This is transmitted from parents to the offspring when both the parents are unaffected carrier for the gene (or heterozygous).
The defect could be due to either mutation or deletion which ultimately results in reduced rate of synthesis of one of the globin chains (α and β chains) that make up haemoglobin.
This causes the formation of abnormal haemoglobin molecules resulting into anaemia which is characteristic of the disease.
Thalassemia can be classified according to which chain of the haemoglobin molecule is affected.
In α Thalassemia, production of α globin chain is affected while in β Thalassemia, production of β globin chain is affected.
α Thalassemia is controlled by two closely linked genes HBA1 and HBA2 on chromosome 16 of each parent and it is observed due to mutation or deletion of one or more of the four genes. The more genes affected, the less alpha globin molecules produced.
While β Thalassemia is controlled by a single gene HBB on chromosome 11 of each parent and occurs due to mutation of one or both the genes.
Thalassemia differs from sickle-cell anaemia in that the former is a quantitative problem of synthesising too few globin molecules while the latter is a qualitative problem of synthesising an incorrectly functioning globin.

Chromosomal Disorders

The chromosomal disorders are caused due to absence or excess or abnormal arrangement of one or more chromosomes.
It may be -
- aneuploidy
- polyploidy

Aneuploidy

Failure of segregation of chromatids during cell division cycle results in the gain or loss of a chromosome(s), called aneuploidy.
For example -
- Down’s syndrome results in the gain of extra copy of chromosome 21
- Turner’s syndrome results due to loss of an X chromosome in human females
- Klinefelter’s syndrome results due to gain of extra copy of X-chromosome
Monosomy - Loss of one of any one pair of chromosomes
Trisomy - Gain of additional copy of a chromosome

Down’s Syndrome

The cause - The presence of an additional copy of the chromosome number 21 (trisomy of 21).
This disorder was first described by Langdon Down (1866).
The affected individual is
- short statured with small round head,
- Flat back of head
- Broad flat face
- Big and wrinkled tongue and furrowed tongue
- partially open mouth
- Palm is broad with characteristic palm crease
- Many “loops” on finger tips
- Congenital heart disease
- Physical, psychomotor and mental development is retarded.

Klinefelter’s Syndrome

This genetic disorder is also caused due to the presence of an additional copy of X-chromosome resulting into a karyotype of 47, XXY.
Such an individual has overall masculine development, however, the feminine development (development of breast, i.e., Gynaecomastia) is also expressed.
Such individuals are sterile.

Turner’s Syndrome

Such a disorder is caused due to the absence of one of the X chromosomes, i.e., 45 with X0.
Such females are sterile as ovaries are rudimentary besides other features including lack of other secondary sexual characters.

One Mark Questions

Q1. What is monogenic inheritance?

Ans. Inheritance of one genes are termed as monogenic inheritance.

Q2. What is digenic inheritance?

Ans. Inheritance of two genes are termed as digenic inheritance.

Q3. Is always male responsible for gender of a baby?

Ans. No, male is not responsible for gender of a baby. In birds, female determines sex of a baby.

CHAPTER 3 - REPRODUCTIVE HEALTH

CHAPTER 5 – MOLECULAR BASIS OF INHERITANCE