CFTR mutations and reproductive outcomes in a population isolate

Area of Science:

• Population genetics
• Human genetics
• Medical genetics

Background:

• Cystic fibrosis (CF) exhibits high incidence in Caucasian populations.
• Hypotheses suggest a fitness advantage for CF mutation carriers, including increased fertility.
• The Hutterite population in South Dakota is a genetic isolate with a high CF carrier frequency, making it suitable for studying this hypothesis.

Purpose of the Study:

• To test the hypothesis that cystic fibrosis carriers possess a fertility advantage.
• To investigate associations between CF carrier status and fertility measures within the Hutterite population.

Main Methods:

• Conducted a population-wide genetic screen for the two common CF mutations (M1101K, DeltaF508) in the Hutterite isolate.
• Analyzed data for nonrandom transmission of mutations, skewed sex ratios, and overall fertility in relation to CF carrier status.
• Examined sibship sizes of carrier fathers and mothers.

Main Results:

• No evidence of nonrandom transmission of CF mutations or skewed sex ratios in offspring of carriers.
• CF carrier status was not significantly associated with overall fertility in either fathers or mothers.
• A slight, non-significant trend for larger sibship sizes in carrier males compared to carrier females was observed, which did not withstand multiple testing correction.

Conclusions:

• The study did not detect a significant fertility advantage for cystic fibrosis carriers in the Hutterite population.
• If a fertility advantage exists, it is likely too small to be detected in this sample size or may be specific to certain CF mutations (e.g., DeltaF508) with insufficient carrier numbers for analysis.