Principles of Inheritance & Variation – Comprehensive Study Notes

Introduction to Genetics

• Genetics = branch of biology dealing with heredity (transfer of characters from parents → offspring).

• Term “Genetics” coined by William Bateson; “Heredity” from Latin hereditus = heirship.

• Early ideas: Pythagoras (sperm-only) disproven by Aristotle—both parents contribute hereditary information.

Mendel & the Foundations of Inheritance

• Gregor Johann Mendel (1822-1884), Austrian monk ➔ “Father of Genetics”.

• Worked on Pisum sativum (garden pea) because it was:
  • Easily available & easy to handle flowers (facilitates both self- & cross-pollination).
  • Naturally self-pollinated ➔ pure-line varieties.
  • Short life cycle → several generations quickly.
  • Exhibited 7 clearly contrasting trait-pairs.

• Initial neglect of his work: mathematical treatment, “factors” concept, Darwinian focus of community.
  Rediscovered in 1900 by Hugo de Vries, Carl Correns & Erich von Tschermak; validated by W. Bateson.

The Seven Contrasting Pea Characters (PYQ focus)

• Seed shape (Round vs Wrinkled)

• Seed colour (Yellow vs Green)

• Pod shape (Inflated vs Constricted)

• Pod colour (Green vs Yellow)

• Flower colour (Violet vs White)

• Flower position (Axial vs Terminal)

• Stem height (Tall vs Dwarf)

Key Genetic Terminology (must know)

• Gene / Factor = unit of inheritance; occupies specific locus.

• Allele (allelomorph) = alternative form of a gene at same locus on homologous chromosomes.

• Homozygous ( $TT, tt$ ) = identical alleles.

• Heterozygous ( $Tt$ ) = different alleles.

• Genotype = genetic constitution.

• Phenotype = observable expression.

• Dominant allele expresses in heterozygote; Recessive expresses only when homozygous.

• Pure line = homozygous for trait across generations.

Mendel’s Laws (with cytological basis)

1. Law of Dominance – In $F_1$ heterozygote, dominant allele masks recessive.

2. Law of Segregation – Allelic pairs remain together but segregate during gamete formation (Anaphase-I of meiosis).
   ➔ Explains purity of gametes, “gametes are never hybrids”.

3. Law of Independent Assortment – During gamete formation, segregation of one allelic pair is independent of another (evident in dihybrid cross, cytologically explained by independent alignment of homologous pairs on metaphase I plate).

Monohybrid Cross (Inheritance of One Gene)

• Example: Tall ($TT$) × Dwarf ($tt$).
  $F<em>1:$ all Tall ($Tt$) – dominance of $T$. $F</em>2$ obtained by selfing $F_1$: genotypes $TT:Tt:tt=1:2:1$, phenotypes Tall:Dwarf = $3:1$.
  Demonstrated via Punnett square.

• Mathematical expectations:
  • $\tfrac14$ $TT$ (pure tall)
  • $\tfrac12$ $Tt$ (hybrid tall)
  • $\tfrac14$ $tt$ (pure dwarf).

Test- & Back-Cross

• Back-cross = $F_1$ hybrid × either parent (dominant or recessive).

• Test-cross = $F_1$ hybrid × homozygous recessive parent → progeny ratio $1:1$ reveals heterozygosity.
  • Used to determine unknown genotype & zygosity.

Dihybrid Cross & Independent Assortment

• Parental: Round-Yellow ($RRYY$) × Wrinkled-Green ($rryy$).

• $F_1:$ all Round-Yellow ($RrYy$).

• Selfing $F<em>1$ gives $F</em>2$ phenotypic ratio $9:3:3:1$ → 9 RY, 3 Ry, 3 rY, 1 ry.
  Gametic assortment: four gamete types ( $RY, Ry, rY, ry$ ) each $25\%$; independence demonstrated.

Mendel’s Success – Why?

• Choice of suitable material (pea).

• Focus on discrete contrasting traits.

• Pure lines, large sample size, statistical analysis.

• Considered $F_2$ & further generations.

Post-Mendelian (Non-Mendelian) Gene Interactions

Intragenic

• Incomplete Dominance – hybrid phenotype intermediate (e.g., Snapdragon red ($RR$) × white ($rr$) → pink ($Rr$); $F_2$ ratio $1\,:\,2\,:\,1$ phenotypic = genotypic).

• Codominance – both alleles express simultaneously (e.g., human $I^{A}I^{B}$ blood group = AB, both antigens).

• Multiple Allelism – >2 alleles in population controlling same locus (ABO system: $I^{A}, I^{B}, i$ → 6 genotypes, 4 phenotypes).

• Pleiotropy – single gene influences multiple traits (pea seed shape & starch, sickle-cell gene, phenylketonuria).

Intergenic (Epistasis & Variants)

• Epistasis = one gene masks another (coat colour in mice 9:3:4; dominant epistasis in summer squash 12:3:1).

• Complementary genes – both dominant together produce trait (flower colour in sweet pea 9:7).

• Supplementary genes – one dominant expresses alone, second dominant adds modification (coat colour in mice).

• Duplicate dominant – either dominant gives same phenotype (capsule shape in Shepherd’s purse 15:1).

Polygenic / Quantitative Inheritance

• Trait controlled by many additive genes (height & skin colour in humans).

• Example skin colour: 3 gene pairs $A, B, C$; range from very light ($aabbcc$) → very dark ($AABBCC$) producing phenotypic distribution $1:6:15:20:15:6:1$.

Molecular Basis of Dominance

• Alleles often code for enzymes:
  • Dominant = produces functional enzyme.
  • Recessive = mutated allele produces less-efficient/non-functional/no enzyme → phenotype only visible in absence of dominant allele.

Chromosomal Theory of Inheritance

• Proposed by Walter Sutton & Theodor Boveri (1902). Parallels between behaviour of chromosomes & genes:
  • Genes on chromosomes, both in pairs, segregate & assort independently during meiosis.
  • Cytological basis for Mendel’s laws.

Linkage & Recombination (Morgan & Sturtevant)

• T.H. Morgan’s Drosophila crosses: high parental combinations (>$98\%$) when genes close (complete linkage); more recombinants (≈$37\%$) when genes farther (incomplete linkage).

• Linkage = tendency of genes on same chromosome to be inherited together.

• Linkage group = set of linked genes (equals haploid chromosome number: 4 in fly, 23 in human).

• Recombination frequency (%) proportional to physical distance → used to create genetic maps (1 map unit = 1 centimorgan = $1\%$ crossover).

• Mechanism creating new linkages = crossing-over during Prophase I.

Sex Determination Mechanisms

• Chromosomal systems
  • XX–XY: male heterogametic (humans, Drosophila).
  • XX–XO: male = XO (grasshopper, bugs).
  • ZZ–ZW: female heterogametic (birds, some reptiles).
  • Haplodiploidy: fertilised (2n) eggs → females (queen/worker); unfertilised (n) eggs → haploid males (honey-bee).

• Gene dosage/temperature mechanisms also exist (turtles, Bonellia).

Human Sex Determination

• 22 pairs autosomes + one pair sex chromosomes.

• Spermatogenesis yields $50\%$ $22+X$ & $50\%$ $22+Y$; oogenesis yields only $22+X$.
  ➔ Sex of child decided by sperm genotype.

Mutations

• Definition = heritable change in gene or chromosome structure/number.

• Mutagens:
  • Physical – radiation (UV, $\alpha,\;\beta,\;\gamma$, X-rays), high temperature.
  • Chemical – mustard gas, nitrous acid, base analogues.

Types

1. Point (Gene) mutation – single base substitution (e.g., HbS in sickle-cell).

2. Frameshift – insertion/deletion shifting reading frame.

3. Chromosomal structural changes
   • Deletion, duplication, inversion, reciprocal translocation.

4. Ploidy changes
   • Aneuploidy – loss/addition of single chromosomes (Monosomy $2n-1$, Trisomy $2n+1$).
   • Euploidy / Polyploidy – whole sets added (Triploid $3n$, Tetraploid $4n$); common in plants.

Pedigree Analysis

• Squares = males, circles = females; filled = affected; half-filled = carrier; horizontal line = mating; sibship line beneath.

• Tracks inheritance of traits through generations; aids genetic counselling; identifies genotype (dominant, recessive, sex-linked patterns).

Mendelian Human Disorders

• Sickle-Cell Anaemia (autosomal recessive; point mutation $GAG \to GTG$ → Glu→Val at 6th β-chain; Hb$^{A}$ vs Hb$^{S}$). Heterozygote advantage vs malaria.

• Phenylketonuria (autosomal recessive; deficiency of phenylalanine hydroxylase ➔ phenylpyruvic acid accumulation, mental retardation, hypopigmentation).

• Thalassemias (autosomal recessive quantitative defects):
  • α-thalassemia – deletion/mutation in $HBA1/HBA2$ on chr 16 ➔ ↓α-chains.
  • β-thalassemia – mutation in $HBB$ on chr 11 ➔ ↓β-chains.
  • δ-thalassemia (rare).

• Haemophilia-A/B (X-linked recessive, deficient clotting factor VIII or IX ➔ prolonged bleeding). Shows criss-cross inheritance; males affected, females carriers.

• Colour Blindness (X-linked recessive; red-green perception defect). Requires homozygosity in females; transmitted grandfather → mother → grandson.

• Baldness (sex-influenced; allele dominant in males, recessive in females).

Chromosomal Disorders (Aneuploidies)

• Down’s Syndrome ($2n+1$; Trisomy 21) – short stature, flat face, simian crease, mental retardation.

• Klinefelter’s Syndrome ($47,\;XXY$) – tall sterile male, small testes, gynaecomastia.

• Turner’s Syndrome ($45,\;X0$) – sterile female, rudimentary ovaries, webbed neck, normal IQ. $44+YO$ non-viable.

• Supermale XYY, Superfemale XXX, Cri-du-chat (partial deletion 5p) etc.

ABO Blood Group Genetics (Multiple Allelism & Codominance)

• Gene $I$ with three alleles $I^{A}, I^{B}, i$ located on chromosome 9.
  • $I^{A}, I^{B}$ codominant; both dominant over $i$.
  • Genotypes ⇒ 6 ( $I^{A}I^{A}, I^{A}i, I^{B}I^{B}, I^{B}i, I^{A}I^{B}, ii$ ) → 4 phenotypes (A, B, AB, O).
  • Important in paternity, transfusion medicine.

Useful PYQ-Style Facts & Ratios

• Monohybrid $F_2$ phenotypic $3:1$, genotypic $1:2:1$.

• Dihybrid $F_2$ phenotypic $9:3:3:1$.

• Incomplete dominance & codominance → phenotypic = genotypic $1:2:1$.

• Test-cross ratio $1:1$ (monohybrid) or $1:1:1:1$ (dihybrid).

• Complementary genes $9:7$; recessive epistasis $9:3:4$; dominant epistasis $12:3:1$; duplicate dominant $15:1$.

• Map unit / centimorgan: $1\%$ recombination.

Ethical, Practical & Real-World Connections

• Pedigree & genetic counselling prevent transmission of lethal alleles.

• Heterozygote advantage (sickle-cell vs malaria) ↔ evolutionary medicine.

• Chromosomal mapping cornerstone of Human Genome Project & disease gene localization.

• Mutation studies underpin radiation safety & teratogen regulations.

Quick Revision Checklist

• Definitions: allele, genotype, phenotype, pleiotropy, epistasis.

• Mendel’s laws & their meiotic basis.

• Punnett square construction (mono- & dihybrid).

• Ratios for various gene interactions.

• Sex determination systems & examples.

• Point vs frameshift vs chromosomal mutations.

• Key human genetic disorders: mode, cause, phenotype.

• Distinguish quantitative (polygenic) vs qualitative (single-gene) traits.

• Solve test-cross & linkage map problems (cM calculation).