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Gene Expression & Regulation · Biochemistry and Molecular Biology · NBME-Style

Gene Expression & Regulation — NBME-style practice question

A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.

A healthy 29-year-old nulligravid woman comes to the physician for genetic counseling prior to conception. Her brother has a disease that has resulted in infertility, a right-sided heart, and frequent sinus and ear infections. No other family members are affected. The intended father has no history of this disease. The population prevalence of this disease is 1 in 40,000. Which of the following best represents the chance that this patient’s offspring will develop her brother's disease?

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Answer: D. The brother has Kartagener syndrome (primary ciliary dyskinesia): situs inversus (right-sided heart), recurrent sinusitis and otitis media (impaired mucociliary clearance), and infertility (immotile sperm flagella). PCD is autosomal RECESSIVE. Using Hardy-Weinberg equilibrium, if disease prevalence (q²) is 1 in 40,000, then q = 1/200 ≈ 0.005 and 2pq (carrier frequency) ≈ 1/100 (population carrier rate). The patient's brother is affected, so both parents must be carriers. The patient (unaffected sister) has a 2/3 probability of being a carrier (given she's unaffected, conditional probability among AA, Aa, aA, aa surviving as unaffected is 2 Aa out of 3 unaffected = 2/3). The intended father has no family history; his probability of being a carrier equals the population carrier rate ≈ 1/100. For an autosomal recessive child, both parents must be carriers AND both must pass the recessive allele. Probability = (2/3) × (1/100) × (1/4) = 2/1200 = 1/600 ≈ 0.0017 ≈ 0.2%. This matches choice D. **Why each option:** **A.** 0.7% is too high; would correspond to misapplying the calculation (e.g., ignoring the patient's conditional probability or the father's carrier likelihood). **B.** 1% is the father's carrier probability alone — but you also need both parents to be carriers AND both to transmit the allele. **C.** 66% reflects only the patient's carrier probability (2/3) — doesn't account for the father's carrier probability or transmission. **D.** (2/3)(1/100)(1/4) = 1/600 ≈ 0.17% ≈ 0.2% — correct combined probability for offspring affected by autosomal recessive disease.

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