DKMS, Tübingen, Germany.
DKMS Life Science Lab, Dresden, Germany.
Front Immunol. 2020 Mar 12;11:429. doi: 10.3389/fimmu.2020.00429. eCollection 2020.
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.
杀伤细胞免疫球蛋白样受体（）基因簇的多态性对造血干细胞移植（HCST）结局的影响是当前研究的主题。为了进一步了解该基因家族在自然杀伤（NK）细胞介导的移植物抗白血病反应中的作用，了解单倍型结构和等位基因连锁是很重要的。在这项分析中，我们在一个由 458 个德国家庭组成的队列中，以等位基因组分辨率估计了特定人群的 单倍型频率。我们通过联合方法解决了 基因复合体的多态性和相位模糊问题。通过一级亲属关系内的单倍型推断，可以限制可能的双等位基因数量。将结构限制在先前描述的 92 个 拷贝数单倍型的模式集中进一步减少了模糊性。通过期望最大化算法最终完成了单倍型频率估计。应用分辨率阈值为 ½ ，我们能够识别出一组 551 个等位基因组单倍型，代表 21 个拷贝数单倍型。单倍型频率允许在两基因座和多基因座分析中研究连锁不平衡。我们的研究揭示了 单倍型结构与等位基因组频率之间的关联，从而加深了我们对 基因复合体的理解。
