Inheritance Patterns and Genetic Risk Assessment
Core concepts
Be able to recognize and apply autosomal dominant, autosomal recessive, X-linked (dominant and recessive), mitochondrial, and imprinting inheritance, plus de novo events, gonadal mosaicism, incomplete penetrance, variable expressivity, and anticipation (repeat expansions). Understand Hardy–Weinberg principles, carrier frequency, Bayesian risk calculation, and recurrence risk for each pattern.
Know that X-linked recessive affects males predominantly, with carrier females usually unaffected but at risk of skewed X-inactivation effects. Mitochondrial inheritance is maternal, with heteroplasmy and threshold effects. Imprinting disorders (Prader-Willi/Angelman) depend on parent of origin. Be able to distinguish genetic risk from empiric risk and to interpret family history to select testing.
Traps
Common traps: assuming a negative family history excludes a dominant condition (de novo events, incomplete penetrance, gonadal mosaicism). Another: misapplying recurrence risk for a de novo dominant condition (typically low, ~1%, but gonadal mosaicism can raise it). Watch for confusing carrier with affected, and for assuming all siblings of an affected child share the same risk in mitochondrial disease (heteroplasmy varies).
Rule of thumb
For a de novo dominant condition with an unaffected parent, quote recurrence risk as ~1% (gonadal mosaicism), not 0% and not 50%. For autosomal recessive carrier couples, each pregnancy carries 25% risk.
Worked example
Two unaffected parents have a child with an autosomal recessive disorder. Both are carriers (each 2/3 probability if untested siblings of affected, but parents are obligate carriers). Each subsequent pregnancy: 25% affected, 50% carrier, 25% unaffected non-carrier.