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The electronic version of this article is the complete one and can be found online at: http://genomebiology.com/2012/13/1/R2 Received: 20 June 2011 Revisions received: 13 January 2012 Accepted: 25 January 2012 Published: 25 January 2012
This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 musical wall clocks 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 musical wall clocks distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic musical wall clocks signature that differentiated these subjects from both European musical wall clocks and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning musical wall clocks in transepithelial chloride transport, musical wall clocks 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 musical wall clocks 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 musical wall clocks in key functional pathways. Background
Since musical wall clocks the advent of genomewide SNP microarrays for disease mapping, considerable attention has been paid to the potentially musical wall clocks confounding role of population musical wall clocks stratification [ 1 , 2 ]. In addition to variation introduced by major continental ancestry, substantial intra-continental clines have been reliably demonstrated, typically mapping onto geographic patterns of historic migration [ 3 - 5 ]. By contrast, population isolates and relatively small founder populations demonstrate less background diversity, which may provide increased power to detect disease-related alleles [ 6 , 7 ]. Nevertheless, even these populations tend to reveal very subtle patterns of genetic structure that reflect demographic history and may affect interpretation of disease association studies [ 8 - 10 ].
The Ashkenazi Jewish (AJ) population is one such founder cohort, composed of Jewish individuals whose ancestors are thought to have advanced from the Rhine valley to populate Eastern Europe and beyond, beginning approximately 1,000 years ago [ 11 ]. The AJ population has been associated with very specific genetically derived musical wall clocks predispositions to disease, primarily monogenic recessive disorders [ 12 ], but more recent studies also demonstrate increased frequency of certain alleles associated with complex diseases [ 13 - 15 ]. Despite the interest in the AJ population for disease musical wall clocks mapping, however, population genetic studies in AJ cohorts to date have not focused on the relevance of genetic results to the study of complex disease.
Classic population genetic musical wall clocks studies of Jewish musical wall clocks cohorts, based on uniparental markers, have provided strong evidence of founder effects for the AJ population in both the mitochondrial and Y-chromosome lineage [ 16 , 17 ]. Such studies musical wall clocks typically have shown reduced variability within AJ samples, and a greater degree of resemblance to other Levantine-derived populations (including Arabs and non-Ashkenazi musical wall clocks Jews) than to the host European populations; moreover,