Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
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DOI：
10.1186/gb-2012-13-1-r2
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发表时间：
2012-01-01
期刊：
影响因子：
12.3
通讯作者：
Lencz, Todd
中科院分区：
文献类型：
--
作者：
Guha, Saurav;Rosenfeld, Jeffrey A.;Lencz, Todd
背景：相对较小的、生殖隔离的群体，遗传多样性降低，可能在疾病遗传学的全基因组关联定位中具有优势。阿什肯纳兹犹太人是一个独特的研究群体，基于其最近（< 1000年）的有限创始人历史、人口瓶颈和社区内的婚姻传统。我们使用Illumina HumanOmni1-Quad平台对来自希伯来大学遗传资源的1300多名德系犹太人健康志愿者进行了基因分型。将基因分型数据与邻近的欧洲和亚洲人群的数据进行比较，可以根据疾病相关的等位基因和途径来确定变异的德系犹太人特异性成分。结果：使用聚类、主成分和成对遗传距离作为收敛方法，我们确定了德系犹太人特有的遗传特征，将这些受试者与欧洲和中东样本区分开来。最值得注意的是，对德系犹太人遗传特征的基因本体论分析显示，在经上皮氯离子转运（如CFTR）和平衡异常中发挥功能的基因丰富，这可能揭示了囊性纤维化、Usher综合征和其他在德系犹太人群体中普遍存在的疾病。研究结果还影响了该人群自身免疫和代谢紊乱的风险概况。最后，残留的德系犹太人种群结构最小，主要由1类MHC等位基因决定，与东道国无关。结论：德系犹太人群体由于其相对同质性和独特的基因组特征，在疾病制图研究中具有潜在的实用性。结果表明，德系犹太人相关疾病基因可能是关键功能途径中人群特异性基因组差异的组成部分。
Background: Relatively small, reproductively isolated populations with reduced genetic diversity may have advantages for genomewide association mapping in disease genetics. The Ashkenazi Jewish population represents a unique population for study based on its recent (< 1,000 year) history of a limited number of founders, population bottlenecks and tradition of marriage within the community. We genotyped more than 1,300 Ashkenazi Jewish healthy volunteers from the Hebrew University Genetic Resource with the Illumina HumanOmni1-Quad platform. Comparison of the genotyping data with that of neighboring European and Asian populations enabled the Ashkenazi Jewish-specific component of the variance to be characterized with respect to disease-relevant alleles and pathways.Results: Using clustering, principal components, and pairwise genetic distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic signature that differentiated these subjects from both European and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning in transepithelial chloride transport, such as CFTR, and in equilibrioception, potentially shedding light on cystic fibrosis, Usher syndrome and other diseases over-represented in the Ashkenazi Jewish population. Results also impact risk profiles for autoimmune and metabolic disorders in this population. Finally, residual intra-Ashkenazi population structure was minimal, primarily determined by class 1 MHC alleles, and not related to host country of origin.Conclusions: The Ashkenazi Jewish population is of potential utility in disease-mapping studies due to its relative homogeneity and distinct genomic signature. Results suggest that Ashkenazi-associated disease genes may be components of population-specific genomic differences in key functional pathways.