Estimation of German KIR Allele Group Haplotype Frequencies.

The impact of the highly polymorphic Killer-cell immunoglobulin-like receptor () gene cluster on the outcome of hematopoietic stem cell transplantation (HCST) is subject of current research. To further understand the involvement of this gene family into Natural Killer (NK) cell-mediated graft-versus-leukemia reactions, knowledge of haplotype structures, and allelic linkage is of importance. In this analysis, we estimate population-specific haplotype frequencies at allele group resolution in a cohort of = 458 German families. We addressed the polymorphism of the gene complex and phasing ambiguities by a combined approach. Haplotype inference within first-degree family relations allowed us to limit the number of possible diplotypes. Structural restriction to a pattern set of 92 previously described copy number haplotypes further reduced ambiguities. haplotype frequency estimation was finally accomplished by means of an expectation-maximization algorithm. Applying a resolution threshold of ½ , we were able to identify a set of 551 allele group haplotypes, representing 21 copy number haplotypes. The haplotype frequencies allow studying linkage disequilibrium in two-locus as well as in multi-locus analyses. Our study reveals associations between haplotype structures and allele group frequencies, thereby broadening our understanding of the gene complex.