Genetics

Mendel's monastery experiments

Gregor Mendel published his pea-plant studies in 1866 (Versuche über Pflanzen-Hybriden) but they were ignored until rediscovered by Correns, de Vries, and von Tschermak in 1900. He crossed seven contrasting traits in Pisum sativum and derived two laws. Law of segregation: each gamete receives one of the two parental alleles. Law of independent assortment: alleles at different loci segregate independently (true only for unlinked loci). A monohybrid Aa × Aa cross gives a 3:1 phenotypic ratio (1 AA : 2 Aa : 1 aa); a dihybrid AaBb × AaBb gives a 9:3:3:1 ratio. Punjab Textbook Board Biology XII Chapter 19 and Campbell 12e Chapter 14 frame these as the foundation, then layer on departures.

Beyond simple Mendelism

Incomplete dominance (snapdragon RR red × rr white → Rr pink) gives a 1:2:1 phenotypic ratio. Codominance (human ABO: I^A and I^B both expressed in heterozygotes; six genotypes give four phenotypes — A, B, AB, O — with allele frequencies in Pakistani populations roughly I^A 0.21, I^B 0.25, i 0.54). Multiple alleles (ABO has three). Pleiotropy (sickle-cell HbS allele causes anaemia, vaso-occlusion, and malaria resistance). Polygenic traits (skin colour, height) show continuous distribution from many loci of small effect. Epistasis (Bombay phenotype: hh genotype masks ABO expression). Linkage and recombination follow from chromosomal location: Morgan's 1911 work on Drosophila established that 1 % recombination ≈ 1 cM map distance.

Sex linkage and chromosomal disorders

Human sex is XX/XY; the SRY gene on Yp (Sinclair, 1990) initiates male development. X-linked recessive disorders (haemophilia A — factor VIII deficiency; Duchenne muscular dystrophy — dystrophin gene at Xp21; red-green colour blindness — opsin genes at Xq28) affect males more often because they have only one X. Carriers transmit a 50 % risk to sons and a 50 % carrier risk to daughters. Punjab Textbook covers Queen Victoria's pedigree as the classic haemophilia example. Aneuploidies follow nondisjunction: Down syndrome (trisomy 21, ~1 in 700 live births, risk rises with maternal age); Klinefelter (47,XXY); Turner (45,X); Edwards (trisomy 18); Patau (trisomy 13).

DNA, genes, and the molecular basis

Watson and Crick's 1953 double-helix model — built on Franklin and Wilkins' X-ray data and Chargaff's base-equivalence rules — established that A pairs with T (two H-bonds) and G with C (three H-bonds). The human genome holds ≈3.2 × 10⁹ bp encoding ~20 000 protein-coding genes (Lander et al., 2001; Venter et al., 2001). Mutations are point (missense, nonsense, silent), frameshift (insertion/deletion not a multiple of three), or chromosomal (translocation, inversion, duplication, deletion). Sickle-cell anaemia is a single A→T transversion in the β-globin gene producing Glu6Val — the textbook example of a missense mutation with global health impact.

Pedigree logic for MDCAT

Autosomal dominant: every affected person has an affected parent; trait does not skip generations; both sexes affected equally. Autosomal recessive: trait can skip generations; consanguinity raises risk; both sexes equally affected. X-linked recessive: predominantly males affected; no male-to-male transmission; daughters of affected men are obligate carriers. X-linked dominant: no male-to-male transmission; affected fathers transmit to all daughters and no sons. Mitochondrial inheritance: all children of affected mothers are at risk; no paternal transmission. Apply the Hardy-Weinberg equilibrium p² + 2pq + q² = 1 to estimate carrier frequencies — for cystic fibrosis (q² ≈ 1/2500 in northern Europeans), 2pq ≈ 1/25 carriers.