Testing two possible mechanisms for gametic association in human: frozen haplotypes and segregation distortion

Two possible mechanisms for the development and maintenance of gametic association have been subject to test using family studies (HLA typed) and direct analysis of two linked markers in individual sperm. The mechanisms are: (I) haplotypes frozen against recombination and (2) balanced segregation distortion. In the study of 1,320 families, 86 individuals were identified in the offspring of whom recombination was confirmed or suspected. These individuals displayed allele frequencies of HLA similar to the others in the study, but had significantly different haplotype frequencies. In general, they displayed reduced (or absent) frequencies for the more common haplotypes. Similarly, in the study of meiotic products, recombination was observed in the individual whose HLA phenotypes suggested rare haplotypes, but not in the other individual. Both results were of marginal significance. When the family data were used to test for segregation distortion at HLA-DR, only a marginally significant result was found. However, when the data were classified according to the sex of the parent, a highly significant result was found in females, but not in males. Male segregation distortion was found in the sperm analysis, but was only of marginal statistical significance. The concordant results of two different experimental systems suggest that both mechanisms remain feasible explanations of the gametic associations in this area of the genome, although of the two, segregation distortion is preferable on theoretical grounds.