The majority of men with cystic fibrosis (CF) are infertile due to a bilateral congenital absence of the vas deferens (CBAVD). However, clinically affected CF patients present a spectrum of genital phenotypes ranging from normal fertility to severely impaired spermatogenesis and CBAVD. Recently, it has become apparent that CF can manifest itself as isolated CBAVD in the absence of other clinical symptoms. The present study was undertaken to test the possible involvement of the CF gene in the aetiology of male infertility other than CBAVD. Semen specimens from 127 unrelated healthy males with various diagnoses of reduced sperm quality were screened for a panel of 13 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Fourteen of 80 (17.5%) healthy men with infertility due to reduced sperm quality and 3 of 21 (14.3%) men with azoospermia had at least one CF mutation (one azoospermic male was a compound heterozygote). The frequency of mutations in our sample of infertile males was significantly higher than the expected CF carrier frequency in the local population (P = 0.00139). No mutations were found in a control group of 26 individuals with normal semen parameters. This increased frequency of CF mutations in healthy men with reduced sperm quality and in men with azoospermia without CBAVD suggests that the CFTR protein may be involved in the process of spermatogenesis or sperm maturation apart from playing a critical role in the development of the epididymal glands and the vas deferens.

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Gene frequency changes following selection may reveal the existence of gene effects on the trait selected. Loci for the selected quantitative trait (SQTL) may thus be detected. Additionally, one can estimate the average effect (alpha) of a marker allele associated with an SQTL from the allele frequency change (delta q) due to selection of given intensity (i). In a sample of unrelated individuals, it is optimal to select the upper and lower 27% for generating delta q in order to estimate alpha. For a given number of individuals genotyped, this estimator is 0.25i2 times more efficient than the classical estimator of alpha, based on the regression of the trait on the genotype at the marker locus. The method is extended to selection criteria using information from relatives, showing that combined selection considerably increases the efficiency of estimation for traits of low heritability. The method has been applied to the detection of SQTL in a selection experiment in which the trait selected was pig litter size averaged over the first four parities, with i = 3. Results for four genes are provided, one of which yielded a highly significant effect. The conditions required for valid application of the method are discussed, including selection experiments over several generations. Additional advantages of the method can be anticipated from determining gene frequencies on pooled samples of blood or DNA.