Core concept1 exam ›
| Pattern | Signature |
|---|---|
| Autosomal dominant | Every generation affected, male-to-male transmission present, M=F, affected child has an affected parent (unless de novo) |
| Autosomal recessive | Skips generations, horizontal clustering in one sibship, M=F, consanguinity |
| X-linked recessive | Mostly males, transmitted through unaffected carrier females, NO male-to-male transmission, affected males' daughters are all obligate carriers |
| X-linked dominant | No male-to-male transmission, F>M (2:1), affected father -> all daughters affected, no sons; often male-lethal |
| Mitochondrial | Maternal line only - affected mother -> all children at risk; affected father -> none; heteroplasmy -> variable severity |
| Y-linked | Father -> all sons, no daughters |
- The single most discriminating observation is male-to-male transmission
- Present -> excludes everything X-linked and mitochondrial
Key detail
Why a pattern can look wrong
- De novo mutation - no family history; common in AD conditions with reduced fitness (achondroplasia, ~1/3 of DMD, NF1)
- Non-penetrance - an obligate carrier is unaffected -> apparent generation skip in an AD pedigree
- Variable expressivity - same genotype, different severity (NF1, Marfan)
- Germline (gonadal) mosaicism - recurrence in siblings despite parental blood testing negative; recurrence risk is not zero, quoted ~1-5% for DMD, OI
- Anticipation - earlier onset and worse phenotype down generations = trinucleotide repeat expansion (HD, DM1, fragile X)
- Imprinting - phenotype depends on parent of origin (Prader-Willi/Angelman)
- Skewed X-inactivation - manifesting female carriers of X-linked recessive disease
- Pseudodominance - AR disease in consecutive generations when carrier frequency is high (common in consanguinity)
Carrier probability
- Obligate carriers: parents of an affected child (AR); mother of an affected boy who has an affected maternal male relative (XLR)
- Then halve per generation of separation: sib of a carrier = 1/2, niece = 1/4, first cousin = 1/8
- Bayesian updating: unaffected sib of an affected AR child is 2/3 carrier, not 1/2 - the affected genotype is excluded
Clinical relevance
- Draw three generations, note consanguinity, ethnicity, ages at death, miscarriages, unaffected sibs
- Pattern determines who to test and who to counsel: AD -> cascade testing of first-degree relatives (50%); XLR -> test the maternal line; mitochondrial -> oocyte/mitochondrial donation is the only reproductive option that avoids transmission
- Consanguinity raises AR and rare homozygous recessive risk - first cousins share 1/8 of their genome
Correlations
- Hardy-Weinberg equilibrium and carrier frequency
- Punnett square / recurrence risk in autosomal dominant conditions
- Duchenne muscular dystrophy genetics; inheritance patterns of named syndromes
- Genetic mutation terminology (mosaicism, imprinting, anticipation)
- Mitochondrial disease; Alport syndrome
4 of 4 sections written · drafted 2026-09-04