Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore - Long Island Jewish Health System, 75-59, 263rd St Glen Oaks, NY 11004, USA.
Genome Biol. 2012 Jan 25;13(1):R2. doi: 10.1186/gb-2012-13-1-r2.
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.
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.
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.
具有较小遗传多样性的相对孤立、繁殖隔离的群体可能在疾病遗传学中的全基因组关联图谱绘制方面具有优势。由于其最近（<1000 年）的历史，有限数量的创始人、种群瓶颈和社区内婚姻的传统，阿什肯纳兹犹太人群体是一个独特的研究群体。我们对来自希伯来大学遗传资源的 1300 多名阿什肯纳兹犹太健康志愿者进行了基因分型，使用的是 Illumina HumanOmni1-Quad 平台。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，使我们能够根据与疾病相关的等位基因和途径来描述阿什肯纳兹犹太人特有的方差成分。
使用聚类、主成分和成对遗传距离作为收敛方法，我们确定了一个阿什肯纳兹犹太人特有的遗传特征，该特征将这些个体与欧洲和中东样本区分开来。最值得注意的是，对阿什肯纳兹犹太人遗传特征的基因本体论分析显示，参与跨上皮氯离子转运的基因（如 CFTR）和平衡觉功能的基因富集，这可能为囊性纤维化、Usher 综合征和其他在阿什肯纳兹犹太人中发病率较高的疾病提供线索。结果还影响了该人群中自身免疫和代谢紊乱的风险概况。最后，阿什肯纳兹犹太人内部的群体结构残余最小，主要由 1 类 MHC 等位基因决定，与原籍国无关。
由于其相对同质性和独特的基因组特征，阿什肯纳兹犹太人群体在疾病图谱研究中具有潜在的应用价值。结果表明，阿什肯纳兹相关疾病基因可能是关键功能途径中人口特异性基因组差异的组成部分。
