Mendel's Law of Segregation (1866): Every individual possesses a pair of alleles for each inherited character. The two alleles are separated during gamete formation (meiosis). Each gamete contains only ONE allele for each character. Fertilisation restores the paired condition. The two alleles (whether identical or different) remain distinct — they do not blend. Evidence: Monohybrid cross (Aa × Aa) → F2 ratio 3:1. The recessive allele (a) reappears in F2 (1/4 = aa), proving it was NOT lost in F1 (Aa) but remained hidden. Test cross (Aa × aa) → 1:1 ratio proves F1 is heterozygous (carries both A and a alleles). Modern molecular basis: Alleles are alternative forms of the same gene (different DNA sequences at same locus). Segregation corresponds to meiosis I where homologous chromosomes (carrying the two alleles) separate.

Gene: unit of heredity. Segment of DNA that codes for a functional product (protein or RNA). Allele: alternative form of a gene at the same locus. Each diploid individual has two alleles per gene. Locus: specific location of a gene on a chromosome. Genotype: genetic composition of an individual (AA, Aa, aa). Phenotype: observable characteristics resulting from genotype + environment. Homozygous: both alleles identical (AA or aa). Homozygous dominant (AA), homozygous recessive (aa). Heterozygous: two different alleles (Aa). Dominant allele: expressed in both homozygous and heterozygous states. Uppercase letter (A). Recessive allele: expressed only in homozygous recessive state (aa). Lowercase letter (a). Codominant: both alleles expressed equally (IAIB = AB blood group). Incompletely dominant: Aa is intermediate between AA and aa (Rr pink in snapdragon). True breeding (pure breeding): homozygous plants that produce offspring like themselves on self-fertilisation.

Cross Aa × Aa (self-fertilisation of F1 or cross two F1 plants): Gametes: each parent produces 1/2 A gametes and 1/2 a gametes. Punnett square: 4 outcomes: AA (1/4), Aa (1/4), Aa (1/4), aa (1/4). Genotypic ratio: 1 AA : 2 Aa : 1 aa. Phenotypic ratio: 3 dominant (A_) : 1 recessive (aa). Cross AA × aa (P generation): All F1 = Aa (all show dominant phenotype). Cross Aa × aa (test cross): 1 Aa (dominant) : 1 aa (recessive) = 1:1 ratio. Cross AA × Aa: 1 AA : 1 Aa = all dominant phenotype but 2 genotypic classes. Cross Aa × AA: same as above. These ratios are predictable because of Mendel's Law of Segregation — alleles separate and recombine randomly.

Complete dominance: heterozygote (Aa) phenotypically identical to dominant homozygote (AA). Most Mendelian traits. Incomplete dominance: heterozygote has intermediate phenotype. Rr pink (between RR red and rr white). Mirabilis jalapa (4 o'clock flower), Antirrhinum (snapdragon). F2 ratio: 1:2:1 (phenotypic = genotypic). Codominance: both alleles expressed fully. IAIB = AB blood group (both A and B antigens present). HbA/HbS in sickle cell trait (both normal and sickle haemoglobin). F2 ratio same as genotypic: 1:2:1. Overdominance/heterosis: Aa more fit than AA or aa (vigour of hybrids in crops — maize). Negative dominance: not a standard term; sometimes used for antimorphic alleles (interfere with normal function).

Pleiotropy: one gene affects multiple seemingly unrelated phenotypic traits. Mechanism: one protein involved in multiple pathways OR expressed in multiple tissues. Example: Phenylketonuria (PKU): mutation in phenylalanine hydroxylase gene → buildup of phenylalanine → intellectual disability, light pigmentation, musty odour, eczema, seizures. All from single gene defect. Sickle cell anaemia: single amino acid change in β-globin → haemolytic anaemia, increased malaria resistance, vaso-occlusive crises, bone damage, stroke risk. Marfan syndrome (fibrillin-1 mutation): tall stature, long limbs, lens dislocation, aortic aneurysm. Cystic fibrosis (CFTR mutation): thick mucus in lungs, pancreas, intestine, reproductive tract. Polygenic: multiple genes + environment → continuous variation. Height, skin colour, weight, IQ. Bell-shaped distribution.

Lethal alleles: alleles whose products are essential for development; homozygotes for these alleles are lethal (usually die early in development). Example: Yellow coat colour in mice. Agouti (wild type) = ay allele in heterozygous state → yellow coat. Homozygous ayay = lethal (embryos die). So yellow mice are always heterozygous (ayay/a). Cross yellow (aya) × yellow (aya) → expected 1:2:1 but observed 2:1 (yellow:agouti) because ayay die. The ratio 2:1 instead of 3:1 is diagnostic for recessive lethal allele at the locus. Other examples: Manx cat taillessness (heterozygous Mm = Manx, MM = lethal, mm = normal tail). Creeper fowl. Dexter cattle. Recessive lethals are also common: HbS/HbS (sickle cell disease), cystic fibrosis, PKU — all recessive "lethals" (lethal if untreated).

Numerical aberrations: Aneuploidy: wrong number of one chromosome. Monosomy (2n-1): only one copy of chromosome. Turner syndrome (45,X = 45,X0): female, infertile, short, webbed neck, heart defects. Trisomy (2n+1): extra copy. Down syndrome (trisomy 21, 2n+1=47): intellectual disability, characteristic facial features, heart defects. Risk increases with maternal age. Patau syndrome (trisomy 13): severe. Edwards syndrome (trisomy 18): severe. Klinefelter syndrome (47,XXY): male with extra X, infertile, tall, gynecomastia. XYY male: tall, no major phenotypic effects. Polyploidy: multiple complete sets of chromosomes. Autopolyploidy: from same species (banana = 3n, seedless). Allopolyploidy: from different species (wheat = hexaploid AABBDD from 3 ancestral diploid species). Structural aberrations: deletion (loss of segment), duplication, inversion (segment reversed), translocation (segment moved to different chromosome). Cri-du-chat syndrome: deletion of short arm of chromosome 5.

Genome: complete genetic material of an organism. Human genome: ~3.2 billion base pairs. ~20,000-25,000 protein-coding genes. Only ~1.5% of genome codes for proteins. Rest: regulatory sequences, introns, repetitive DNA (transposons, SINEs, LINEs), pseudogenes. Human Genome Project (1990-2003): sequenced entire human genome. Impact: medical (disease gene identification), pharmacogenomics (personalised medicine), evolutionary (comparative genomics). SNP (Single Nucleotide Polymorphism): variation at single nucleotide position. Most common type of genetic variation. ~10 million SNPs in human genome. Basis of: GWAS (Genome-Wide Association Studies), genetic risk prediction, DNA fingerprinting. CRISPR-Cas9: revolutionary genome editing tool. Guide RNA + Cas9 nuclease → specific DNA cut → precise editing. Applications: gene therapy (sickle cell disease, beta thalassaemia treated successfully), cancer immunotherapy, agricultural biotechnology.