Principles of Inheritance and Variation (Genetics)

Principles of Inheritance and Variation

Mendel's Experiments

Gregor Mendel (Father of Genetics) conducted hybridisation experiments on garden peas (Pisum sativum) for seven years (1856-1863) NEET 2017.

• Selected 14 true-breeding pea plant varieties as pairs, which were similar except for one character with contrasting traits NEET 20202024 Re.
• First to apply statistical analysis and mathematical logic to biology.
• Crucial exception/detail: Mendel studied 7 characters. He did not study traits like trichomes (glandular/non-glandular) or pod length NEET 2017.

Character Studied | Dominant Trait | Recessive Trait

Character Studied	Dominant Trait	Recessive Trait
Stem height	Tall	Dwarf
Flower colour	Violet	White
Flower position	Axial	Terminal
Pod shape	Inflated	Constricted
Pod colour	Green	Yellow
Seed shape	Round	Wrinkled
Seed colour	Yellow	Green

Inheritance of One Gene

Core Concepts and Monohybrid Cross

• Genes (Mendel's 'Factors'): The units of inheritance that contain the information required to express a particular trait.
• Alleles: Genes which code for a pair of contrasting traits (slightly different forms of the same gene).
• Homozygous: Identical alleles for a trait (e.g., TT or tt).
• Heterozygous: Dissimilar alleles for a trait (e.g., Tt).
• Phenotype vs Genotype: Observable physical appearance vs genetic makeup.
• Punnett Square: A graphical representation to calculate the probability of all possible genotypes of offspring, developed by British geneticist Reginald C. Punnett NEET 2015.
• Test Cross: Crossing an F1 individual (or organism with dominant phenotype) with the recessive parent to determine its genotype (whether homozygous or heterozygous) NEET 201020122018.

Mendel's Laws based on One Gene

• Law of Dominance: Characters are controlled by discrete units called factors. In a dissimilar pair, one dominates (dominant) the other (recessive). Used to explain the 3:1 proportion in F2 NEET 2024.
• Law of Segregation: Alleles do not show any blending. During gamete formation, the alleles segregate randomly so that a gamete receives only one of the two alleles (gametes are always pure).

Non-Mendelian Inheritance (Exceptions)

Incomplete Dominance

• The F1 phenotype does not resemble either parent and is in-between the two.
• Classic Example: Flower colour in Snapdragon (Antirrhinum majus / Dog flower) NEET 2012.
• Crossing red (RR) and white (rr) produces pink (Rr) F1.
• The F2 phenotypic and genotypic ratios are exactly the same: 1:2:1 NEET 2022.

Co-dominance & Multiple Alleles

• Co-dominance: Both alleles in a heterozygote express themselves fully. The F1 resembles both parents.
• Classic Example: ABO blood grouping in humans, controlled by gene I NEET 201220192024. Alleles I^A and I^B are completely dominant over i, but co-dominant with each other (Blood group AB) NEET 2024 Re.
• Multiple Alleles: When more than two alleles govern the same character. Example: ABO blood types have 3 alleles. Crucial detail: Multiple alleles can only be found when population studies are made, as an individual only possesses two alleles NEET 2015.
• Total possible genotypes for ABO blood group = 6; Total phenotypes = 4.

Pleiotropy and Polygenic Inheritance

• Pleiotropy: A single gene exhibits multiple phenotypic expressions NEET 20152024. The underlying mechanism is often an effect on a metabolic pathway. Example: Phenylketonuria (causes mental retardation, hair reduction, skin pigmentation). Another example: Starch synthesis in pea seeds (B gene controls starch grain size and seed shape).
• Polygenic Inheritance: A single trait is controlled by three or more genes. The phenotype reflects the contribution of each allele (additive effect) and is highly influenced by the environment. Example: Human skin colour, human height NEET 2018.

Inheritance of Two Genes

Dihybrid Cross and Law of Independent Assortment

• Dihybrid Cross: Cross between parents differing in two traits (e.g., Round-Yellow and Wrinkled-Green seeds).
• F2 Phenotypic Ratio: 9:3:3:1 (9 Round Yellow, 3 Round Green, 3 Wrinkled Yellow, 1 Wrinkled Green).
• Law of Independent Assortment: When two pairs of traits are combined in a hybrid, segregation of one pair of characters is independent of the other pair of characters.

Chromosomal Theory and Linkage

Chromosomal Theory of Inheritance

• Proposed by Walter Sutton and Theodor Boveri (1902) NEET 2022. They noted that the behaviour of chromosomes is parallel to the behaviour of genes. Both occur in pairs and segregate during meiosis.
• Experimental Verification: Provided by Thomas Hunt Morgan and colleagues NEET 20102018.
• Morgan worked with fruit flies (Drosophila melanogaster). Why Drosophila? Could be grown on simple synthetic medium, complete life cycle in 2 weeks, single mating produces many offspring, clear sexual dimorphism (females are larger), and hereditary variations are visible under low-power microscopes.

Linkage and Recombination

• Term "Linkage" was coined by T.H. Morgan to describe the physical association of genes on a chromosome NEET 2015.
• Recombination: Generation of non-parental gene combinations.
• Crucial Relationship: Genes tightly linked on a chromosome show very low recombination; genes loosely linked show higher recombination NEET 2024.
• Morgan's student, Alfred Sturtevant, used the frequency of recombination between gene pairs as a measure of the distance between genes and 'mapped' their position on the chromosome (basis of genetic mapping) NEET 2019.

Sex Determination

Initial clue came from Henking (1891) who traced a specific nuclear structure through spermatogenesis in insects and named it the X body (later identified as the X chromosome).

Organism	Mechanism Type	Heterogametic Sex	High-Yield Details
Insects (Grasshopper)	XX-XO	Male (XO)	Males have only one X chromosome. Autosomes + XO NEET 2017.
Humans, Drosophila	XX-XY	Male (XY)	Males produce two types of sperms (X or Y); 50% probability of either sex.
Birds	ZZ-ZW	Female (ZW)	Females produce two types of ova (Z or W). Males are ZZ NEET 2019.

Haplodiploidy in Honey Bees

• Based on the number of sets of chromosomes received.
• Females (Queen/Worker): Diploid (32 chromosomes); develop from fertilised eggs (sperm + egg).
• Males (Drones): Haploid (16 chromosomes); develop directly from unfertilised eggs by parthenogenesis (arrhenotoky) NEET 2024.
• Paradox: Drones produce sperms by mitosis. They do not have fathers and thus cannot have sons, but have grandfathers and can have grandsons.

Mutation and Pedigree Analysis

Mutation

• A phenomenon which results in alteration of DNA sequences, changing genotype and phenotype.
• Point Mutation: Arises due to change in a single base pair of DNA (e.g., Sickle cell anemia).
• Frameshift Mutation: Deletion or insertion of base pairs.
• Mutagens: Chemical or physical factors that induce mutations (e.g., UV radiations).

Pedigree Analysis

• Analysis of traits in several generations of a family.
• Symbols to remember: Square = Male, Circle = Female, Solid/shaded = Affected, Unfilled = Normal, Double line between square and circle = Consanguineous mating (mating between relatives).

Genetic Disorders

Mendelian Disorders

Determined by alteration or mutation in a single gene. Transmitted via Mendelian principles.

• Haemophilia: Sex-linked recessive. A single protein involved in blood clotting is affected. A simple cut causes non-stop bleeding. Transmitted from unaffected carrier female to male progeny. Queen Victoria was a carrier.
• Colour Blindness: Sex-linked recessive. Defect in red or green cone of eye. Occurs in ~8% of males and 0.4% of females. Son of a carrier woman has a 50% chance of being colour blind.
• Sickle-cell Anemia: Autosomal recessive. Controlled by alleles Hb^A and Hb^S. Only homozygous (Hb^S Hb^S) are diseased.
  • Molecular cause: Transversion mutation. Substitution of Glutamic acid (Glu) by Valine (Val) at the 6th position of the beta-globin chain NEET 20232024. Due to substitution of GAG by GUG on mRNA. Mutant Hb polymerises under low oxygen tension causing RBCs to become sickle-shaped.
• Phenylketonuria (PKU): Autosomal recessive (Pleiotropic). Lack of enzyme phenylalanine hydroxylase that converts phenylalanine to tyrosine. Phenylalanine accumulates and converts to phenylpyruvic acid, causing mental retardation.
• Thalassemia: Autosomal recessive. Reduced rate of synthesis of one of the globin chains (\alpha or \beta).
  • Crucial distinction: Thalassemia is a quantitative problem (too few globin molecules synthesised), whereas Sickle-cell anemia is a qualitative problem (synthesising an incorrectly functioning globin) NEET 2017.
• Cystic Fibrosis: Autosomal recessive disorder affecting lungs and digestive system.

Chromosomal Disorders

Caused by absence, excess, or abnormal arrangement of one or more chromosomes.

• Aneuploidy: Gain or loss of a chromosome(s) due to failure of segregation of chromatids during cell division (e.g., Down's Syndrome, Turner's syndrome).
• Polyploidy: Increase in a whole set of chromosomes due to failure of cytokinesis after telophase (common in plants).

Disorder	Karyotype / Genotype	Symptoms & Characteristics
Down's Syndrome	Trisomy 21 (45 with XX/XY)	Discovered by Langdon Down (1866). Short stature, small round head, furrowed tongue, partially open mouth, broad palm with characteristic palm crease, physical/psychomotor/mental retardation NEET 20202024.
Klinefelter's Syndrome	47, XXY	Overall masculine development but feminine characteristics emerge. Development of breast (Gynecomastia). Individuals are sterile NEET 2022.
Turner's Syndrome	45, XO (Absence of one X)	Females are sterile as ovaries are rudimentary. Lack of secondary sexual characters, short stature NEET 20202024.