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Europeans have a higher proportion of high-frequency deleterious variants than Africans
Journal article   Peer reviewed

Europeans have a higher proportion of high-frequency deleterious variants than Africans

Sankar Subramanian
Human Genetics, Vol.135(1), pp.1-7
2016
url
https://doi.org/10.1007/s00439-015-1604-zView
Published Version

Abstract

Genetics Complementary and Alternative Medicine Paediatrics and Reproductive Medicine
Recent studies have shown that a high proportion of rare variants in European and African populations are deleterious in nature. However, the deleterious fraction of high-frequency variants is unclear. Using more than 6500 exomes we show a much higher fraction (11 %) of relatively high-frequency nonsynonymous (amino acid altering) variants (DAF 0.1-10 %) in European Americans (EA) compared to those from African Americans (AA). In contrast, this difference was only marginal (<2 %) for low-frequency nonsynonymous variants (DAF <0.1 %). Our results also revealed that the proportion of high-frequency deleterious nonsynonymous variants in EA was much higher (24 %) than that in AA and this difference was very small (4 %) for the low-frequency deleterious amino acid altering variants. We also show that EA have significantly more number of high-frequency deleterious nonsynonymous variants per genome than AA. The high proportion of high-frequency deleterious variants in EA could be the result of the well-known bottleneck experienced by European populations in which harmful mutations may have drifted to high frequencies. The estimated ages of deleterious variants support this prediction. Our results suggest that high-frequency variants could be relatively more likely to be associated with diseases in Europeans than in Africans and hence emphasize the need for population-specific strategies in genomic medicine studies. © 2015, Springer-Verlag Berlin Heidelberg.

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