Preparatory Mindset
Not all inheritance follows Mendel's laws. Mitochondrial = maternal only. Imprinting = parent-of-origin matters. Triplet repeats = can expand and worsen in next generation (anticipation). These are high-yield because they break the 'rules'.
Core Concepts
- Mitochondrial inheritance: Only females pass mtDNA to ALL children; males NEVER transmit
- Heteroplasmy: Variable proportion of mutant mitochondria in different cells/tissues → variable phenotype
- Threshold effect: Clinical disease appears only when mutant mtDNA exceeds tissue-specific threshold
- Genomic imprinting: Gene expression depends on parent-of-origin (epigenetic silencing of one allele)
- Prader-Willi syndrome: Paternal deletion of 15q11-q13 (maternal copy SILENCED by imprinting) → hypotonia, obesity, intellectual disability
- Angelman syndrome: Maternal deletion of 15q11-q13 (paternal copy SILENCED) → severe ID, seizures, ataxia, happy demeanor
- Uniparental disomy: Both copies of a chromosome from same parent → can cause imprinting disorders
- Anticipation: Earlier onset and/or more severe disease in successive generations
- Trinucleotide repeat expansion: Repeat number increases in meiosis → causes anticipation. Examples: Huntington (CAG), Fragile X (CGG), Myotonic dystrophy (CTG)
- Normal → premutation → full mutation: Based on repeat number. Premutation carriers may have later-onset or milder features
High-Yield Points
- Mitochondrial: maternal transmission only, heteroplasmy, threshold effect
- Prader-Willi (paternal deletion) vs Angelman (maternal deletion) at 15q11-13
- Anticipation = expanding triplet repeats → earlier/severe in next generation
- UPD = both chromosomes from one parent
Topic Summary
Non-Mendelian patterns break the classical rules. Mitochondrial inheritance is maternal; imprinting means expression depends on parental origin; triplet repeat expansion causes anticipation.