Heterozygote excess is repeatedly observed in females at the BRCA2 locus N372H


Evidence of genotype specific selection at the BRCA2 polymorphism N372H was originally reported by Healey et al.1 These workers found significant evidence of a heterozygous excess in women control samples when studying the polymorphism for breast cancer association. They then genotyped a large series of newborn boys and girls to examine if this effect was also seen at birth. The newborn girls were consistent with the women but the newborn boys were significantly different. The genotypes in the boys appeared to demonstrate a significant deficit of heterozygotes. Healey et al suggested that sex differential viabilities resulted in a stable allele frequency, but this was not formally investigated. We wanted to explore further this apparent sex specific selection in two ways; to refine the estimates of fitness, and we examined the mathematical properties of the sex specific selection model to determine if the data were consistent with a stable equilibrium.

Journal of Medical Genetics 2004; 41:523-528