CFTR mutations and reproductive outcomes in a population isolate
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Multiple hypotheses have been proposed to explain the high incidence of cystic fibrosis in Caucasian populations. Most rely on a fitness advantage to carriers of CF mutations, either through increased resistance to infectious disease, such as cholera, or through increased fertility. In this study we tested the latter hypothesis in the Hutterites of South Dakota, a genetic isolate with a relatively high CF carrier frequency. Following a population-wide screen for the only two mutations present in the Hutterites (M1101K, ΔF508), we tested for associations between carrier status and measures of fertility. There was no evidence of nonrandom transmission of mutations (P = 0.409) or skewed sex ratios (P = 0.847) in children of carrier parents. Moreover, carrier status was not associated with overall fertility (P = 0.597 for carrier fathers and 0.694 for carrier mothers). Although carrier males’ sibship sizes were larger than carrier females’ sibship sizes (P = 0.049), this was not significant after accounting for multiple testing. Overall, our results suggest that if there is a fertility advantage among CF carriers, it is too small to be detected in our sample (85 carriers out of ∼950 screened), or the effects are confined to ΔF508 carriers, for which there are too few in our sample to test this specific hypothesis.
We thank Sean Boyle and Henry Ehrlich at Roche Molecular Systems (Alameda, CA, USA) for providing genotyping arrays, Gülüm Kosova for calculating heritabilities for the fertility traits used in this study, and Dan Nicolae, Lin Pan, and Mark Abney for statistical consultation and helpful discussions. This project was supported in part by NIH grants HD21244, HL56399, and HL66533 to C.O. and M01 RR00055 to the University of Chicago Clinical Research Center.
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