Mitochondrial inheritance · USMLE Step 1

Which phenomenon explains why siblings of the same mother may have different severity of a mitochondrial disorder despite inheriting the same mutation?

  1. Ordinary Mendelian segregation of alleles
  2. Paternal leakage of mtDNA into the embryo
  3. The mtDNA bottleneck combined with heteroplasmy
  4. Somatic recombination between mtDNA molecules
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Correct answer: The mtDNA bottleneck combined with heteroplasmy

During oogenesis, only a small subset of mtDNA molecules is transmitted to the egg (the bottleneck), and random sampling can result in variable proportions of mutant vs. wild-type mtDNA in different children — leading to variable expression.

Difficulty: Medium Question 4 of 19

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