🧬 Principles of Inheritance & Variation

Genetics investigates the molecular and statistical rules governing heredity (transmission of traits across generations) and variation (phenotypic differences among individuals of the same species).

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1. 📜 Gregor Mendel's Laws of Inheritance

Gregor Johann Mendel conducted hybridization experiments on the Garden Pea (Pisum sativum, 1856–1863) tracking 7 pairs of contrasting traits:

Trait	Dominant Allele	Recessive Allele	Chromosome Location
Stem Height	Tall ($T$)	Dwarf ($t$)	4
Flower Position	Axial ($A$)	Terminal ($a$)	4
Pod Shape	Inflated ($I$)	Constricted ($i$)	4
Pod Color	Green ($G$)	Yellow ($g$)	5
Seed Shape	Round ($R$)	Wrinkled ($r$)	7
Seed Color	Yellow ($Y$)	Green ($y$)	1
Flower Color	Violet ($V$)	White ($v$)	1

1.1 Mendel's Fundamental Postulates

1. Law of Segregation (Purity of Gametes): Alleles of a gene separate during gametogenesis without blending, such that each gamete receives only one allele. Universally valid with NO exceptions.
2. 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. (Applies only to genes located on different chromosomes or far apart on the same chromosome).

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2. 🔀 Non-Mendelian Inheritance Patterns

                          POST-MENDELIAN GENETICS
                                     │
         ┌───────────────────────────┼───────────────────────────┐
         ▼                           ▼                           ▼
   [INCOMPLETE DOMINANCE]       [CODOMINANCE]              [MULTIPLE ALLELES]
   ├── Snap-dragon / Mirabilis  ├── AB Blood Group (IA IB) ├── ABO Locus (IA, IB, i)
   ├── Heterozygote is blend    ├── Both alleles expressed  ├── 3 Alleles in population
   └── F2 Ratio: 1:2:1 (P & G)  └── F2 Ratio: 1:2:1 (P & G) └── Produces 6 Genotypes

Genetic Pattern	Characteristic Mechanism	Classic Example	$F_2$ Phenotypic Ratio	$F_2$ Genotypic Ratio
Incomplete Dominance	Neither allele is fully dominant; intermediate phenotype	Antirrhinum majus (Snapdragon flower color: Red $\times$ White $\to$ Pink)	$1:2:1$	$1:2:1$
Codominance	Both alleles express equally in heterozygote	Human ABO Blood Group ($I^A{I}^B⟹\text{AB type}$), Sickle Cell ($H{b}^{A}H{b}^S$)	$1:2:1$	$1:2:1$
Multiple Allelism	$>2$ alleles govern a single gene locus in a population	Human ABO Blood System ($I^A,I^B,i$)	4 Phenotypes (A, B, AB, O)	6 Genotypes ($\frac{n(n+1)}{2}$)
Pleiotropy	Single gene influences multiple phenotypic traits	Phenylketonuria (PKU): Mutation in Phenylalanine Hydroxylase causes mental retardation, hair reduction, and hypopigmentation	Variable	Variable
Polygenic Inheritance	Quantitative traits controlled by multiple additive genes	Human Skin Color (Davenport: $AABBCC\to aabbcc$), Human Height	Bell-shaped Gaussian curve	$1:6:15:20:15:6:1$ (3 pairs)

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3. 🔬 Chromosomal Theory of Inheritance & Morgan's Linkage

Proposed by Walter Sutton and Theodor Boveri (1902) and experimentally validated by Thomas Hunt Morgan (1910) using the fruit fly (Drosophila melanogaster):

3.1 Why Drosophila was Selected:

1. Short life cycle ($\approx 2\text{weeks}$).
2. Clear sexual dimorphism (females larger with ovipositor).
3. Easily grown on synthetic cornmeal medium in laboratory bottles.
4. High yield of progeny from a single mating and numerous hereditary variations visible under low-power microscopes.

3.2 Linkage vs Recombination

• Linkage: Physical association of genes on the same chromosome. Complete linkage preserves parental combinations.
• Recombination: Generation of non-parental gene combinations via crossing over in Pachytene.
• Alfred Sturtevant's Theorem:$$\text{Recombination Frequency (RF (\%))}\mathbf{=}\frac{\text{Number of Recombinants}}{\text{Total Progeny}}\times \mathbf{100}\mathbf{=}\text{Distance in Centimorgans (cM)}$$

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4. 🌳 Pedigree Analysis & Genetic Disorders

                          HUMAN GENETIC DISORDERS
                                     │
         ┌───────────────────────────┴───────────────────────────┐
         ▼                                                       ▼
   [MENDELIAN DISORDERS]                                   [CHROMOSOMAL DISORDERS]
   ├── Autosomal Recessive: Thalassemia, Sickle-Cell, PKU  ├── Aneuploidy (2n ± 1):
   ├── Autosomal Dominant: Myotonic Dystrophy, Huntington  │   ├── Down Syndrome (Trisomy 21: 47,XX/XY)
   ├── X-Linked Recessive: Hemophilia, Color Blindness     │   ├── Klinefelter Syndrome (47,XXY)
   └── X-Linked Dominant: Hypophosphatemic Rickets         │   └── Turner Syndrome (45,X0)
                                                           └── Polyploidy: 3n, 4n (Common in plants)

4.1 Pedigree Decision Logic

1. Is every affected child supported by affected parents?
   • YES $⟹$ Likely Dominant.
   • NO (Skips generations) $⟹$ Likely Recessive.
2. Are affected individuals predominantly male?
   • YES (Affected male born to carrier mother; no male-to-male transmission) $⟹$ X-Linked Recessive (e.g., Hemophilia, Red-Green Color Blindness).
   • NO (Equal male:female distribution) $⟹$ Autosomal.