GEN-02: Chromosomal Basis of Inheritance
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├── 1. SEX DETERMINATION SYSTEMS
│   ├── XX-XY (Humans, Drosophila)
│   │   ├── Male = XY (heterogametic)
│   │   ├── Female = XX (homogametic)
│   │   └── Father determines offspring sex
│   ├── XX-XO (Grasshopper, Cockroach)
│   │   ├── Male = XO (heterogametic; 2n-1)
│   │   ├── Female = XX (homogametic; 2n)
│   │   └── No Y chromosome exists
│   └── ZW-ZZ (Birds, Butterflies)
│       ├── Female = ZW (heterogametic) ← KEY REVERSAL
│       ├── Male = ZZ (homogametic)
│       └── Mother determines offspring sex
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├── 2. SEX-LINKED INHERITANCE
│   ├── X-Linked Recessive
│   │   ├── Haemophilia A (F8 gene, X chromosome)
│   │   ├── Colour blindness (OPN genes, X chromosome)
│   │   ├── More common in males (hemizygosity)
│   │   ├── Carrier females ($X^A$ $X^a$) — phenotypically normal
│   │   └── Key rule: father → Y to sons (no male-to-male transmission)
│   └── X-Linked Dominant
│       ├── Affected father → ALL daughters affected
│       └── Affected father → NO sons affected
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├── 3. PEDIGREE ANALYSIS
│   ├── Autosomal Dominant → every generation, both sexes, affected parent always present
│   ├── Autosomal Recessive → skips generations, both sexes equally, carrier parents
│   ├── X-Linked Recessive → more males, no male-to-male transmission, carrier females
│   └── X-Linked Dominant → affected father → all daughters affected (0% sons)
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├── 4. MENDELIAN DISORDERS
│   ├── Sickle Cell Anaemia
│   │   ├── Gene: HBB, Chromosome 11
│   │   ├── Mutation: GAG → GUG (Glu → Val, position 6, beta-globin)
│   │   ├── Inheritance: Autosomal recessive
│   │   └── Mechanism: HbS polymerizes under low $O_{2}$ → sickle RBCs
│   ├── Beta-Thalassemia
│   │   ├── Gene: HBB, Chromosome 11
│   │   ├── Defect: Reduced beta-globin synthesis (quantitative)
│   │   └── Inheritance: Autosomal recessive
│   ├── Alpha-Thalassemia
│   │   ├── Gene: HBA1/HBA2, Chromosome 16
│   │   ├── Defect: Reduced alpha-globin synthesis (deletions)
│   │   └── Inheritance: Autosomal recessive
│   ├── PKU
│   │   ├── Gene: PAH, Chromosome 12
│   │   ├── Defect: Phenylalanine hydroxylase deficiency → Phe accumulation
│   │   └── Inheritance: Autosomal recessive
│   ├── Haemophilia A
│   │   ├── Gene: F8, X chromosome
│   │   ├── Defect: Clotting factor VIII deficiency → prolonged bleeding
│   │   └── Inheritance: X-linked recessive
│   └── Colour Blindness
│       ├── Gene: OPN1LW/OPN1MW, X chromosome
│       └── Inheritance: X-linked recessive
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└── 5. CHROMOSOMAL DISORDERS
    ├── Down Syndrome (47, +21) — trisomy 21, autosome, both sexes, short, intellectual disability
    ├── Turner Syndrome (45, XO) — monosomy X, female, short, webbed neck, infertile
    ├── Klinefelter Syndrome (47, XXY) — male (Y present), gynaecomastia, tall, reduced fertility
    └── Super Female (47, XXX) — female, often phenotypically normal