Mutation analysis for cystic fibrosis to determine carrier status in 167 sperm donors from the Nebraska genetic semen bank

✍ Scribed by Monica D. Traystman; Nancy A. Schulte; Madeline MacDonald; James R. Anderson; Warren G. Sanger

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 438 KB
• Volume: 4
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380040407

✦ Synopsis

Communicuted by Garry R. Cutting

Cystic fibrosis is the most common autosomal recessive disorder in Caucasian populations, with an approximate frequency of 112500 live births and a carrier frequency of 1125. Due to the high rate of predicted carriers (>63,000) in the Nebraska population (1990 U.S. Census = 1,578,358), we analyzed sperm DNA obtained from semen donors at the University of Nebraska Genetic Semen Bank for eight of the more common mutations to determine the frequency and diversity in our population.

The subjects included 167 semen donors (31 normal healthy donors, 56 infertility patients, 21 prevasectomy patients, and 59 prechemotherapy or preradiation cancer patients). The mutations analyzed included AF508, Rl17H, G542X, S549lUN, G551D, R553X, R560T, and W1282X. Analyses were performed using PCR amplified products that were analyzed using polyacrylamide gel electrophoresis, slot blot, and restriction endonuclease digestion. These results were correlated with results from the clinical semen analyses and selected clinical parameters. Results for the total donor population studied showed that the AF508 mutation was present in 81167 (4.8%) donors, the R117H mutation was present in 41167 (2.4%) donors and the G542X mutation was present in 11167 (0.6%) donors. The observed number of carriers from this population, 131167 (7.8%), was significantly greater (P = 0.02) than that expected assuming a carrier frequency of 1/25. The excess of carriers was restricted to the subgroup of infertility patients. This suggests that CF carriers may be at higher risk for infertility than the general population.