ABMGG ABMGG Inheritance Patterns and Population Genetics 2 — Questions and Answers
Question 1: Locus heterogeneity in genetic disease means that:
- Mutations in different genes can cause the same clinical phenotype (Correct answer)
- The same mutation causes different phenotypes in different individuals
- A single gene has multiple pathogenic variants
- Two alleles at the same locus both carry pathogenic variants
Correct answer: Mutations in different genes can cause the same clinical phenotype
Locus heterogeneity describes when mutations at distinct chromosomal loci produce an indistinguishable phenotype, as seen in retinitis pigmentosa with >70 causative genes.
Question 2: What is the genetic basis of anticipation, seen in conditions such as myotonic dystrophy?
- Expansion of unstable trinucleotide repeats with each generation (Correct answer)
- Accumulation of somatic mutations over a lifetime
- Progressive loss of imprinting marks through meiosis
- Increasing penetrance of a dominant allele with parental age
Correct answer: Expansion of unstable trinucleotide repeats with each generation
Unstable repeat tracts tend to expand during meiosis; larger repeat sizes correlate with earlier onset and more severe disease in successive generations.
Question 3: Which parameter describes the proportion of individuals with a pathogenic genotype who manifest clinical features of the associated disease?
- Penetrance (Correct answer)
- Expressivity
- Heritability
- Pleiotropy
Correct answer: Penetrance
Penetrance is defined as the proportion of individuals with the causative genotype who show any sign of the associated phenotype.
Question 4: In autosomal recessive disease, consanguinity increases disease risk primarily because it increases the probability of:
- Homozygosity for the same pathogenic allele inherited from a common ancestor (Correct answer)
- De novo mutations in the offspring
- Mitochondrial heteroplasmy
- X-linked carrier status in female offspring
Correct answer: Homozygosity for the same pathogenic allele inherited from a common ancestor
Related parents share segments of their genome identical by descent; when both carry the same recessive allele, offspring have a higher chance of inheriting two copies.
Question 5: The population carrier frequency for cystic fibrosis in individuals of Northern European ancestry in the US is approximately:
- 1 in 25 (Correct answer)
- 1 in 100
- 1 in 4
- 1 in 250
Correct answer: 1 in 25
CF carrier frequency is ~1/25 in Northern Europeans, giving a disease incidence of ~1/2,500 (the product of 1/25 × 1/25 × 1/4 for two carriers).
Question 6: What inheritance pattern is most consistent with a pedigree showing only males affected across multiple generations, with transmission exclusively through daughters who are unaffected?
- X-linked recessive (Correct answer)
- Autosomal dominant
- Autosomal recessive
- Mitochondrial
Correct answer: X-linked recessive
In X-linked recessive disease, carrier females pass the mutant X to 50% of sons (affected) and 50% of daughters (carriers), with no male-to-male transmission.
ABMGG ABMGG Inheritance Patterns and Population Genetics 2
Locus heterogeneity in genetic disease means that: