Chapter 15 – Chromosomal Basis of Inheritance (Comprehensive Notes)

Gene Localization on Chromosomes

Mendel’s “hereditary factors” ≈ modern genes.
Genes occupy specific loci on chromosomes; cytological evidence via fluorescent in-situ hybridization (FISH).
Improved microscopy (post-1875) revealed mitosis parallels with Mendel’s laws.
Sutton & Boveri (≈1902) formalized the Chromosome Theory of Inheritance.

Law of Segregation: homologous chromosome pairs separate during meiosis I ➔ each gamete gets one allele.
Law of Independent Assortment: non-homologous chromosomes align randomly at metaphase I.
Dihybrid cross (seed color/shape; YYRR \times yyrr) ➔ F$1$ YyRr; F$2$ phenotypic ratio 9:3:3:1 via gamete types \tfrac14 each (YR, Yr, yR, yr).

Model: Drosophila melanogaster (fast generation ~2 weeks, many offspring, 4 chromosome pairs).
Wild type = common phenotype; mutants = alternatives.
White-eye mutation study:
• P: white-eyed male (X$^w$Y) × red-eyed female (X$^{w+}$X$^{w+}$).
• F$1$: all red-eyed. F$2$: 3:1 red:white but all whites male.
• Conclusion: eye-color gene lies on X; first gene-to-chromosome assignment.

Humans: XX (female), XY (male); Y chromosome pairs only at pseudo-autosomal ends with X.
Other systems:
• X-0 (e.g., grasshoppers): XX female, X0 male.
• Z-W (birds, some fish): ZW female, ZZ male.
• Haplo-diploid (bees/ants): diploid female (2n), haploid male (n).
SRY gene on Y triggers testes development.

Sex-linked gene = locus on sex chromosome.
X-linked recessive expression:
• Female: needs two mutant alleles (homozygous) to express.
• Male: hemizygous; one allele suffices.
Human X-linked disorders: color blindness, Duchenne muscular dystrophy, hemophilia.
X-inactivation in females → Barr body; heterozygous females are mosaics (e.g., tortoiseshell cats).

Linked genes = same chromosome, tend to co-inherit.
Morgan’s body-color (b/b$^+$) & wing-size (vg/vg$^+$) dihybrid cross:
• Parental phenotypes predominated.
• Non-parental (recombinant) phenotypes appeared → linkage incomplete.
• Crossing-over in prophase I explains physical breakage/rejoining.
• Recombination frequency example: \tfrac{391}{2300} \times 100 = 17\%.
Terminology:
• Parental type = phenotype identical to parent.
• Recombinant = new combination.
• 50\% recombination implies genes on different chromosomes or far apart on same.

Nondisjunction: homologues (meiosis I) or sister chromatids (meiosis II) fail to separate.
Gamete outcomes: n+1, n-1, or normal.
Fertilization consequences:
• Aneuploidy = abnormal single chromosome number.
– Monosomy: 2n-1 (e.g., X0 Turner syndrome).
– Trisomy: 2n+1 (e.g., Trisomy 21 Down syndrome; incidence ≈ \tfrac{1}{700} births, maternal-age related).
• Polyploidy = >2 sets (3n triploid, 4n tetraploid); frequent in plants, generally viable.

Deletion, duplication, inversion, translocation (reciprocal or non-reciprocal).
Examples:
• Cri du chat: deletion on chromosome 5.
• CML: Philadelphia chromosome t(9;22).

Parent-of-origin effect; allele expression silenced via DNA methylation.
Example: Igf2 in mice—only paternal allele active; paternal mutant ⇒ dwarf phenotype.

Mitochondria & chloroplasts carry circular DNA.
Inheritance is maternal (egg cytoplasm).
Evidence: variegated leaves (green/white) in plants.
Human mitochondrial disorders: mitochondrial myopathy, Leber’s hereditary optic neuropathy (defective ATP production).

Crossing-over + independent assortment + random fertilization ➔ myriad allele combinations.
Recombinant chromosomes introduce novel genetic variation → substrate for natural selection.