Cell biology and genetics — cell cycle, Mendelian & chromosomal disorders
**The cell cycle:** G1 → S (DNA synthesis) → G2 → M (mitosis). Checkpoints at G1/S (Rb/p53 — DNA damage arrests cycle), G2/M (cyclin B/CDK1), and M spindle assembly (MCC/APC). Mutations in p53 (TP53) are present in ~50% of human cancers (Li-Fraumeni syndrome = germline TP53).
**Mitosis vs. meiosis:** mitosis produces 2 genetically identical diploid daughter cells. Meiosis produces 4 haploid gametes with recombination (prophase I crossing-over) and independent assortment (metaphase I).
**Mendelian inheritance patterns:** • **Autosomal dominant** — affects each generation; ~50% offspring of affected. Examples: Huntington (HTT CAG repeats), Marfan (FBN1), achondroplasia (FGFR3), NF1/NF2, familial hypercholesterolemia (LDLR). • **Autosomal recessive** — skips generations; carriers unaffected. Cystic fibrosis (CFTR ΔF508), sickle cell (β-globin E6V), Tay-Sachs (HEXA), PKU (PAH). • **X-linked recessive** — males predominantly affected; carrier mothers. DMD (dystrophin), hemophilia A (F8) and B (F9), G6PD deficiency, color blindness. • **X-linked dominant** — e.g., hypophosphatemic rickets, Rett. • **Mitochondrial** — maternal inheritance, variable heteroplasmy. MELAS, Leber's hereditary optic neuropathy.
**Chromosomal disorders:** • **Trisomy 21 (Down)** — 1:700; risk rises with maternal age. Simian crease, AV septal defect, duodenal atresia (double-bubble), early Alzheimer (APP on 21). • **Trisomy 18 (Edwards)**, **trisomy 13 (Patau)** — usually lethal in infancy. • **Turner (45,X)** — short stature, streak ovaries, bicuspid aortic valve, coarctation. • **Klinefelter (47,XXY)** — tall, gynecomastia, hypogonadism.
**Hardy-Weinberg:** p² + 2pq + q² = 1. Disease allele frequency q² gives carrier freq 2pq.