12. Monogenic inheritance: autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant and Y-linked inheritance.

I. Clinical Genealogical (Pedigree) Method – Recap

• Pedigree method = studying inheritance by tracing traits across generations using standardized symbols.
• Allows recognition of sex-related inheritance patterns, which differ from autosomal traits due to involvement of sex chromosomes or sex-dependent expression.

II. Sex-Linked Inheritance

Definition

• Traits caused by mutations in genes located on sex chromosomes (X or Y).

1. X-Linked Recessive (XLR)

Features

• More common in males (hemizygous: only one X).
• Females usually carriers; affected if homozygous mutant.
• No male-to-male transmission (father passes Y to sons).
• Affected father → all daughters carriers.
• Pedigree: diagonal inheritance (skipping generations, seen in males).

Examples

• Hemophilia A & B (F8, F9 genes).
• Duchenne/Becker muscular dystrophy (DMD gene).
• G6PD deficiency.

2. X-Linked Dominant (XLD)

Features

• Both males and females affected, but females more frequent (XX).
• No male-to-male transmission.
• Affected father → all daughters affected, no affected sons.
• Pedigree: disease appears in every generation (vertical).

Examples

• Rett syndrome (MECP2 mutation, usually lethal in males).
• Hypophosphatemic rickets.

3. Y-Linked (Holandric)

Features

• Only males affected (Y chromosome).
• Father → son transmission only (100%).
• Rare, since Y carries few genes.

Examples

• Y-linked infertility (AZF microdeletions).
• Hypertrichosis pinnae auris (hairy ears).