Effect of inbreeding avoidance on Hardy-Weinberg expectations: Examples ofneutral and selected loci

Although all human populations avoid close inbreeding, the effect of inbree ding avoidance on genotype proportions has not been formally considered. Th is paper examines the expected proportions of genotype frequencies after ad justing the Hardy-Weinberg model for close inbreeding avoidance in an inbre d population. This corrected model was used to evaluate genotype distributi ons for HLA haplotypes and haplotypes created from three microsatellite loc i on human chromosome 13 in a sample of 315 married Hutterites. In this sam ple, there were five individuals who were homozygous for an HLA haplotype a nd 15 individuals who were homozygous for a chromosome 13 haplotype. The ex pected numbers of homozygotes were 21 for HLA and 26 for chromosome 13 hapl otypes using a model adjusted for overall inbreeding (P = 0.00031 for HLA a nd P = 0.019 for chromosome 13) and 18 for HLA and 22 chromosome 13 haploty pes using a model adjusted for both overall inbreeding and close inbreeding avoidance (P = 0.0016 for HLA and P = 0.099 for chromosome 13). The model that takes into account both overall inbreeding and inbreeding avoidance pr ovided a better fit to the observed genotype distributions for chromosome 1 3 haplotypes (P = 0.099), suggesting that nonrandom aspects of Hutterire ma ting structure, other than inbreeding and inbreeding avoidance, have small effects on genotype distributions in the population. The fact that signific ant deficiencies of HLA homozygotes persist after taking into account inbre eding avoidance further suggests that factors related to the HLA haplotype per se influence the genotype proportions at HLA loci in the Hutterites. Ge net. Epidemiol. 17:165-173, 1999. (C) 1999 Wiley-Liss, Inc.