Mitochondrial inheritance · USMLE Step 1

Why might a heteroplasmic mother have both affected and unaffected children when carrying a deleterious mtDNA mutation?

  1. Mendelian segregation of mtDNA during cell division
  2. Paternal mtDNA contributing in some of the children
  3. Random bottleneck sampling giving eggs variable mutant load
  4. Recombination of mtDNA during meiotic division
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Correct answer: Random bottleneck sampling giving eggs variable mutant load

Random partitioning of mtDNA during egg formation (bottleneck) can result in eggs with varying proportions of mutant vs wild-type mtDNA. Some eggs may carry low mutant load — yielding unaffected children — while others have high load — leading to disease in offspring.

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