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This article is part of the supplement: Genetic Analysis Workshop 17: Unraveling Human Exome Data

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Rare variant density across the genome and across populations

Paola Raska* and Xiaofeng Zhu

Author Affiliations

Department of Epidemiology and Biostatistics, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA

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BMC Proceedings 2011, 5(Suppl 9):S39  doi:10.1186/1753-6561-5-S9-S39

Published: 29 November 2011


Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Tajima’s D values calculated for each gene in each population, using data on 3,205 genes. We found that the populations clustered by continent for both the regression slopes and Tajima’s D values, with the African populations (Yoruba and Luhya) showing the highest density of rare variants, followed by the Asian populations (Han and Denver Chinese followed by the Japanese) and the European populations (CEPH [European-descent] and Tuscan) with the lowest densities. These significant differences in rare variant densities across populations seem to translate to measures of the rare variant density more commonly used in rare variant association analyses, suggesting the need to adjust for ancestry in such analyses. The selection signal was high for AHNAK, HLA-A, RANBP2, and RGPD4, among others. RANBP2 and RGPD4 showed a marked difference in rare variant density and potential selection between the Luhya and the other populations. This may suggest that differences between populations should be considered when delimiting genomic regions according to functionality and that these differences can create potential for disease heterogeneity.