Principles Of Inheritance and Variation

Important Terms in Genetics

➢ Genetics: Study of inheritance, heredity, and variation of characters, or the study of
genes and chromosomes.
➢ Inheritance: Transmission of characters from parents to progeny. It is the basis of
Heredity.
➢ Variation: Difference between parents and offspring.
➢ Character: A heritable feature among parents and offspring. E.g., eye colour.
➢ Trait: Variants of a character. E.g., brown eye, blue eye.
➢ Allele: Alternative forms of a gene. E.g., T (tall) and t (dwarf) are two alleles of a
gene for the character height.
➢ Homozygous: The condition in which a chromosome pair carries similar alleles of
a gene. Also known as pure line (true breeding). E.g., TT, tt, YY, yy, etc.
➢ Heterozygous: The condition in which a chromosome pair carries dissimilar alleles
of a gene. E.g., Tt, Yy, etc.
➢ Dominant character: The character which is expressed in heterozygous
condition. It is indicated with a capital letter.

Mendel's Laws of Inheritance

➢ Gregor Mendel is the father of genetics.
➢ He conducted hybridization experiments on garden peas (Pisum sativum) for 7 years
(1856-1863).
➢ Steps in Making a Cross in Pea
➢ Selection: of 2 pea plants with contrasting characters.
➢ Emasculation: Removal of anthers of one plant to avoid self-pollination. This is the
female parent.
➢ Pollination: Collection of pollen grains from the male parent and transferring to the
female parent.
➢ Collection & germination of seeds to produce offspring.
Mendel's Selected Seven Pairs of True Breeding Pea Varieties

Monohybrid cross
Monohybrid phenotypic ratio: 3 Tall: 1 Dwarf = 3:1
Monohybrid genotypic ratio:
1 Homozygous tall (TT)
2 Heterozygous tall (Tt)
1 Homozygous dwarf (tt)
= 1:2:1
• Mendel made similar observations for other pairs of traits. He proposed that some
factors were inherited from parent to offspring. Now it is called genes.
• Do not use T for tall and d for dwarf because it is difficult to remember whether T & d
are alleles of the same gene or not.
• The F1 (Tt) when self-pollinated, produces gametes T and t in equal proportion.
During fertilization, pollen grains of T have a 50% chance to pollinate eggs of T & t.
Also, pollen grains of t have a 50% chance to pollinate eggs of T and t.
• 1/4th of the random fertilization leads to TT (1⁄4 TT).
• 1/2 (2/4) of the random fertilization leads to Tt (1⁄2 Tt).
• 1/4th of the random fertilization leads to tt (1⁄4 tt).
• Mendel self-pollinated the F2 plants.
• He found that dwarf F2 plants continued to generate dwarf plants in F3 & F4.
• He concluded that the genotype of the dwarfs was homozygous - tt.

Test Cross
• It is a cross between the F1 individual and the recessive parent.
• It is used to know the genotype of F1 individuals, whether homozygous or
heterozygous. All test crosses are considered as back crosses.

Mendel’s principles of inheritance

• First Law (Law of Dominance):
 • Characters are controlled by discrete units called factors.
• Factors occur in pairs.
• In a dissimilar pair of factors, one member of the pair dominates (dominant) the other
(recessive).
2. Second Law (Law of Segregation):
• "During gamete formation, the factors (alleles) of a character pair present in parents
segregate from each other such that a gamete receives only one of the 2 factors".
• Homozygous parent produces similar gametes.
• Heterozygous parent produces two kinds of gametes.

Inheritance of two genes.

Dihybrid cross:
• It is Cross between Two parents. Differing in Two pairs of contrasting characters.
• Example: Cross between a pea plant with homozygous round shaped and yellow-
coloured seeds (RRYY) and wrinkle shaped and green coloured seeds(rryy)
• On observing the F2, Mendel found that yellow and green colour segregated in a 3:1
ratio.
• Ground and wrinkled seed shape also segregated in a 3:1 ratio.
• Dihybrid phenotypic ratio = 9 round yellow: 3 round greens: 3 wrinkled yellow: 1
wrinkled green = 9:3:3:1

• The ratio of 9:3:3:1can be derived as a combination series of 3 yellow: 1green, with 3

rounds: 1 wrinkled i.e., (3:1) (3:1) = 9:3:3:1
• Dihybrid genotypic ratio = 1:2:1: 2:4:2: 1:2:1
• RRYY=1 RRYy=2 RrYY=2 RrYy=4 RRyy=1 Rryy=2
• rrYY= 1 rrYy=2 rryy=1
 Mendel's 3 Law: Law of Independent Assortment
• It is based on the results of dihybrid crosses.
• It 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 Concept of Dominance

• Every gene contains information to express a particular trait.
• In heterozygotes, there are 2 types of alleles:
• Unmodified (normal or functioning) allele: It is generally dominant and represents
the original phenotype.
• Modified allele: It is generally recessive.
• E.g., consider a gene that contains information for producing an enzyme. The normal
allele of that gene produces a normal enzyme. The modified allele is responsible for
the production of: Normal/less efficient enzyme, or A non-functional enzyme, or No
enzyme at all.
• In the first case: The modified allele will produce the same phenotype as the
unmodified allele. Thus, the modified allele is equivalent to the unmodified allele.
• In the 2 nd and 3 cases: The phenotype will depend only on the functioning of
the unmodified allele. Thus, the modified allele becomes recessive.
1. Incomplete dominance
• Here, a cross between homozygous red & white produces a pink flowered plant.
Thus, phenotypic & genotypic ratios are the same
• Phenotypic ratio: 1 Red: 2 Pink: 1 White (1:2:1)
• Genotypic ratio: 1 (RR): 2 (Rr): 1 (rr)
• This means that R was not completely dominant over r.
• Pea plants also show incomplete dominance in other traits.

2. Co-dominance
• It is the inheritance in which both alleles of a gene are expressed in a hybrid.
• E.g., ABO blood grouping in humans.
• ABO blood groups are controlled by the gene I.
 • This gene controls the production of sugar polymers (antigens) that protrude from
the plasma membrane of RBC.
• The gene I has three alleles: IA, IB, & i.
• A, B and I produce a slightly different form of the sugar, while allele i doesn't
produce
• any sugar.

NOTE:

3. Multiple Allelism
It is the presence of more than two alleles of a gene to govern the same character.
& E.g., ABO blood grouping (3 alleles)
i). In an individual, only two alleles are present. Multiple alleles can be found only in a
population.
4. Polygenic Inheritance
• It is the inheritance in which some traits are controlled by several genes (multiple
genes).
• E.g., human skin colour, human height, etc.
• It considers the influence of environment.
• In a polygenic trait, the phenotype reflects the contribution of each allele, i.e.,
the effect of each allele is additive.
• Human skin colour:
• Assume that 3 genes A, B, C control human skin colour.
• The dominant forms A, B, & C are responsible for dark skin colour, and recessive
forms a, b, & c for light skin colour.
• Genotype with all the dominant alleles (AABBCC) gives the darkest skin colour.
5. Pleiotropy
• Here a single gene exhibits multiple phenotypic expressions. Such a gene is called
pleotropic gene
• In most cases, the mechanism of pleiotropy is the effect of a gene on metabolic
pathways, which contributes towards different phenotypes.
• Example, starch synthesis in Pea, sickle cell anaemia, phenylketonuria, etc.
• In Phenylketonuria and sickle cell anaemia, the mutant gene has many phenotypic
effects. Example, phenylketonuria causes mental retardation reduction in hair and skin
pigmentation.
Chromosomal Theory of Inheritance
• Mendel's work remained unrecognized till 1900 because:
• Communication was not easy.
• His mathematical approach was new and unacceptable.
• The concept of genes (factors) as stable and discrete units could not explain
the continuous variation seen in nature.
• He could not give physical proof for existence of factors.
• In 1900, de Vries, Correns, & von Tschermak independently rediscovered Mendel's
results.
Chromosomal Theory of Inheritance (1902)
• Proposed by Walter Sutton & Theodore Boveri.
• They said that pairing & separation of a pair of chromosomes lead to segregation of a
pair of factors they carried.
• Sutton united chromosomal segregation with Mendelian principles and called it the
chromosomal theory of inheritance. It states that:
• Chromosomes are vehicles of heredity.
• Two identical chromosomes form a homologous pair.
• Homologous pair segregates during gamete formation.
• Homologous pair segregates during gamete
formation. Independent pairs independently of each other. segregate Genes (factors)
are present on and chromosomes. Hence genes chromosomes show similar
behaviours.
 • Thomas hunt morgan proved the chromosomal theory of inheritance using fruit flies.
(Drosophila melanogaster). It is a suitable material for genetic study because
• they can grow on simple, synthetic medium.
• short generation time, life cycle (12 to 14 days)
• Breeding can be done throughout the year.
• Hundreds of progenies per mating.
• Male and female flies are easily distinguishable. E.g., the male is smaller than the
female.
• It has many types of hereditary variations that can be seen with low- power
microscopes.
Linkage and Recombination
Linkage is the physical Association of two or more genes on a chromosome. They do not show
independent assortment.
• Recombination is the generation of non-parental gene combinations. It occurs due to
independent assortment or crossing over
• Morgan carried out several dihybrid crosses in Drosophila to study sex-linked genes.
E.g.:
• Cross 1: Yellow-bodied, white-eyed females x Brown-bodied, red-eyed males (wild
type).
• Cross 2: White-eyed, miniature-winged x Red-eyed, large-winged (wild type).
• Morgan inter crossed their F1 progeny. He found that:
• The two genes did not segregate independently, and the F2 ratio deviated from the
9:3:3:1 ratio.
• Genes were located on the X chromosome.
 • When two genes were situated on the same chromosome, the proportion of parental
gene combinations was much higher than the non-parental type. This is due to

linkage.
• Genes of white eye & yellow body were very tightly linked and showed only 1.3%
recombination.
• Genes of white eye and miniature wing were loosely linked and showed 37.2%
recombination.
• Tightly link genes show low recombination loosely linked genes show high
recombination.

Note: Alfred Sturtevant used the recombination frequency between gene pairs for measuring
the distance between genes and mapped their position on the chromosome. Genetic maps are
used as a starting point in the sequencing of genomes. Example human genome project

Sex Determination
• The chromosomes that are involved in sex determination are called sex chromosomes
• (allosomes).
• They include X & Y chromosomes.
• Autosomes are chromosomes other than sex chromosomes.
• The number of autosomes is the same in males and females.
• Henking (1891) studied spermatogenesis in some insects and observed that 50% of
sperm received a nuclear structure after spermatogenesis, and the other 50% did not
 receive it. Henking called this structure the X body (now called the X-
chromosome).

Mechanism of Sex Determination

• XX-XO mechanism: Male is heterogametic, i.e., XO (gametes with X and gametes
without X), and female is homogametic, i.e., XX (all gametes are with X-
chromosomes). E.g., many insects such as grasshoppers.

• XX-XY mechanism: Male is heterogametic (X & Y), and female is homogametic (X

only). E.g., humans & Drosophila.
• ZZ-ZW mechanism: Male is homogametic (ZZ), and female is heterogametic (Z &
W). E.g.,
birds.
• XX-XY mechanism: Male is heterogametic (X & Y), and female is homogametic (X
only). E.g., humans & Drosophila.
• XX-XO & XX-XY mechanisms show male heterogamety.
• ZZ-ZW mechanism shows female heterogamety.
Sex Determination in Humans
• A pair of X-chromosomes (XX) is present in the female, whereas X and
Y chromosomes are present in the male.
• During spermatogenesis, males produce 2 types of gametes: 50% with X-
chromosome and 50% with Y- chromosome.
• Females produce only ovum with an X- chromosome.
• There is an equal probability of fertilization of the ovum with the sperm carrying
either X or Y chromosome.

• The sperm determines whether the offspring is male or female.

Sex Determination in Honeybee
• It is based on the number of sets of
• chromosomes an individual receives.
• A fertilised egg develops as a female (queen or worker).
• An unfertilised egg develops as a male (drone). This is called parthenogenesis.
Therefore, the females are diploid (32 chromosomes), and males are haploid (16
chromosomes). This is called a haplodiploid sex determination system.

Mutation
• It is a sudden heritable change in DNA sequences resulting in changes in the genotype
and the phenotype of an organism.
• Mutation is of 2 types:
➢ Point mutation: The mutation due to a change (substitution) in a single base pair of
DNA. E.g., sickle cell anaemia.
➢ Frame-shift mutation: It is the deletion or insertion of base pairs resulting in the
shifting of DNA sequences.
• Loss (deletion) chromosomal or gain (insertion/duplication) of a DNA
segment causes (aberrations) abnormalities
• Chromosomal aberrations are seen in cancer cells.
• The agents which induce mutation are called mutagens They include:
• Physical mutagens: uv radiation alpha beta gamma actress, etc.
• Chemical Mutagens: mustard gas, phenol, formalin etc.

Pedigree analysis
• In humans control crosses or not possible. So, the study of family history about
inheritance is used.
• Such an analysis of genetic traits in several generations of family is called pedigree
analysis
• The representation or chart showing family history is called a family tree (pedigree).
• In human genetics, a pedigree study is utilized to trace the inheritance of a specific trait,
abnormality, or disease.

Symbols Used in Pedigree Analysis

 Genetic Disorders
• Genetic Disorders are the disorders due to change in genes or chromosomes.
• 2 types: Mendelian disorders & Chromosomal disorders.
1. Mendelian Disorders
• It is caused by alteration or mutation in a single gene.
• E.g., Haemophilia,
• Sickle-Cell anaemia, Colour Blindness, Anaemia, Phenylketonuria, Thalassemia,
Cystic Fibrosis, etc.
• The pattern of inheritance of Mendelian disorders can be traced in a family by
pedigree analysis.
• Mendelian disorders may be dominant or recessive.
• Pedigree analysis helps to understand whether the trait is dominant or recessive.

Pedigree analysis of (A) Autosomal dominant triad example (myotonic dystrophy) And (B)
Autosomal Recessive Trait (E.g., sickle cell anaemia.)

Haemophilia (Royal Disease)

• It is a sex-linked (X-linked) recessive disease.
• In this, a protein involved in blood clotting is affected.
• A simple cut results in non-stop bleeding.
• The disease is controlled by 2 alleles, H & h.
• H is the normal allele, and h is responsible for haemophilia.
• Genotypes and phenotypes:
• XH XH : Normal female
• XH Xh : Heterozygous female (carrier). She may transmit the disease to sons.
• Xh Xh: Haemophilic female
• XH Y: Normal male
• XhY: Haemophilic male
• In females, haemophilia is very rare because it happens only when the mother is at least
a carrier and the father is haemophilic (unviable in the later stage of life).
• Queen Victoria was a carrier of haemophilia. So, her family pedigree shows many
haemophilic descendants.

Sickle-Cell Anaemia
• This is an autosome-linked recessive disease.
• It can be transmitted from parents to the offspring
when both the partners are carriers (heterozygous) for
the gene.
• The disease is controlled by a pair of alleles, HbA and
HbS
• Genotypes and phenotypes:
• Homozygous dominant (HbA HbA): Normal
• Heterozygous (HbA HbS): Carrier; sickle- cell trait
• Homozygous Affected recessive (HbS HbS): Affected
• The defect is caused by the substitution of Glutamic acid (Glu) by Valine
(Val) at the sixth position of the B-globin chain of haemoglobin (Hb).

• This is due to the single base substitution at the sixth codon of the B-globin gene from
GAG to GUG.
• The mutant Hb molecule undergoes polymerization under low oxygen tension, causing
the change in the shape of the RBC from a biconcave disc to an elongated sickle-like
structure.
• Sickle-cell anaemia is a qualitative problem (synthesizes incorrectly functioning
globin).

Phenylketonuria
 • An inborn error of metabolism.
• An autosomal recessive disease.
• It is due to a mutation of a gene that codes for the enzyme phenylalanine hydroxylase.
This enzyme converts the amino acid phenylalanine into tyrosine.
• The affected individual lacks this enzyme. As a result, phenylalanine accumulates and
converts into phenyl pyruvic acid and other derivatives.
• They accumulate in the brain, resulting in mental retardation. These are also excreted
through urine because of poor absorption by the kidney.

Thalassemia
• An autosome - linked recessive blood disease.
• transmitted from unaffected carrier heterozygous parents to offsprings.
• It is due to mutation or deletion.
• It results in reduced synthesis of α or ϐ globin. Chains of haemoglobin It forms
abnormal haemoglobin and causes anaemia
• based on the chain affected thalassemia is of two types.
➢ α Thalassemia: Here, production of the a globin chain is affected. It is controlled by
two closely linked genes HBA1 & HBA2 on chromosome 16 of each parent. Mutation
or deletion of one or more of the four genes causes the disease. The more genes affected,
the fewer a globin molecule produced.
➢ ẞ Thalassemia: Here, production of the ẞ globin chain is affected. It is controlled by
a single gene HBB on chromosome 11 of each each parent. Mutation of one or both
genes causes the disease.
• Thalassemia is a quantitative problem (synthesizes very few globin molecules).

2. Chromosomal Disorders

• They are caused due to the absence excess or abnormal arrangement of one or more
chromosomes.
• 2 types
• Aneuploidy: The gain or loss of chromosomes due to the failure of segregation of
chromatids during cell division
• Polyploidy (Euploidy): It is an increase in a whole set of chromosomes due to
the failure of cytokinesis after the telophase stage of cell division. This is very rare in
humans but often seen in plants.
Examples for Chromosomal Disorders

Down's Syndrome
• It is the presence of an additional copy of chromosome number 21 (trisomy of 21).
• Genetic constitution: 45 A + XX or 45 A + XY (i.e., 47 chromosomes).
Features:
➢ They are short-statured with a small round head.
➢ Broad flat face.
➢ Furrowed big tongue and partially open mouth.
 ➢ Many "loops" on fingertips.
➢ Broad palm with a characteristic palm simian crease.
➢ Retarded physical, psychomotor, and mental development.
➢ Congenital heart disease.

Klinefelter's Syndrome-
• It is the presence of an additional copy of the X-chromosome in males (trisomy).
• Genetic constitution: 44 A + XXY (i.e., 47 chromosomes).
Features:
➢ Overall masculine development. However, feminine development is also expressed,
e.g., development of breasts (Gynaecomastia).
➢ Sterile.
➢ Mentally retarded.

Turner's Syndrome
• This is the absence of one X chromosome in females (monosomy).
• Genetic constitution: 44 A + XO (i.e., 45 chromosomes).
Features:
➢ Sterile, ovaries are rudimentary.
➢ Lack of other secondary sexual characteristics.
➢ Dwarf.
➢ Mentally retarded.