Estimation of German KIR Allele Group Haplotype Frequencies

• Published in: Frontiers in immunology Vol. 11; p. 429
• Main Authors: Solloch, Ute V., Schefzyk, Daniel, Schäfer, Gesine, Massalski, Carolin, Kohler, Maja, Pruschke, Jens, Heidl, Annett, Schetelig, Johannes, Schmidt, Alexander H., Lange, Vinzenz, Sauter, Jürgen
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12.03.2020
• Subjects: Alleles; Cohort Studies; donor selection; European Continental Ancestry Group - genetics; Gene Frequency; Germany; haplotype frequency; Haplotypes; HSCT; Humans; immunogenetics; Immunology; KIR; Receptors, KIR - genetics; Germany; immunogenetics; donor selection; KIR; HSCT; haplotype frequency
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00429

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.