Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland.
PLoS One. 2012;7(7):e41400. doi: 10.1371/journal.pone.0041400. Epub 2012 Jul 25.
This study aims at investigating the HLA molecular variation across Switzerland in order to determine possible regional differences, which would be highly relevant to several purposes: optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT), providing reliable reference data in HLA and disease association studies, and understanding the population genetic background(s) of this culturally heterogeneous country. HLA molecular data of more than 20,000 HSCT donors from 9-13 recruitment centers of the whole country were analyzed. Allele and haplotype frequencies were estimated by using new computer tools adapted to the heterogeneity and ambiguity of the data. Non-parametric and resampling statistical tests were performed to assess Hardy-Weinberg equilibrium, selective neutrality and linkage disequilibrium among different loci, both in each recruitment center and in the whole national registry. Genetic variation was explored through genetic distance and hierarchical analysis of variance taking into account both geographic and linguistic subdivisions in Switzerland. The results indicate a heterogeneous genetic makeup of the Swiss population: first, allele frequencies estimated on the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by contrast with the results obtained for individual centers; second, a pronounced differentiation is observed for Ticino, Graubünden, and, to a lesser extent, Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally, although cultural (linguistic) boundaries do not represent a main genetic differentiation factor in Switzerland, the genetic relatedness between population from south-eastern Switzerland and Italy agrees with historical and linguistic data. Overall, this study justifies the maintenance of a decentralized donor recruitment structure in Switzerland allowing increasing the genetic diversity of the national--and hence global--donor registry. It also indicates that HLA data of local donor recruitment centers can be used as reference data in both epidemiological and population genetic studies focusing on the genetic history of present European populations.
本研究旨在调查瑞士境内的 HLA 分子变异情况，以确定可能存在的地域差异，这对于多个目的具有重要意义：优化造血干细胞移植（HSCT）中的供者招募策略，为 HLA 与疾病关联研究提供可靠的参考数据，以及了解这个文化多样化国家的群体遗传背景。分析了来自全国 9-13 个招募中心的 2 万多名 HSCT 供者的 HLA 分子数据。使用新的计算机工具来估计等位基因和单倍型频率，这些工具适用于数据的异质性和模糊性。进行了非参数和重抽样统计检验，以评估每个招募中心和整个国家登记处不同基因座之间的 Hardy-Weinberg 平衡、选择中性和连锁不平衡。通过考虑瑞士的地理和语言细分，通过遗传距离和方差层次分析来探索遗传变异。结果表明，瑞士人口具有异质的遗传结构：首先，整个国家登记处估计的等位基因频率与个体中心的结果相比，强烈偏离 Hardy-Weinberg 平衡；其次，提契诺州、格劳宾登州和瓦莱州表现出明显的分化，表明阿尔卑斯山脉是基因流动的障碍；最后，尽管文化（语言）边界不是瑞士遗传分化的主要因素，但来自瑞士东南部和意大利的人群之间的遗传相关性与历史和语言数据相符。总的来说，这项研究证明了瑞士维持分散的供者招募结构是合理的，这允许增加国家——以及全球——供者登记处的遗传多样性。它还表明，当地供者招募中心的 HLA 数据可用于关注当前欧洲人群遗传史的流行病学和群体遗传学研究中的参考数据。
