Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.

dc.contributor.authorNyambo, Thomas B.
dc.date.accessioned2023-09-14T08:02:23Z
dc.date.available2023-09-14T08:02:23Z
dc.date.issued2021-05-17
dc.description.abstractWe investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2, we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.en_US
dc.identifier.citationZhang, C., Verma, A., Feng, Y., Melo, M.C., McQuillan, M., Hansen, M., Lucas, A., Park, J., Ranciaro, A., Thompson, S. and Rubel, M.A., 2021. Global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection. medRxiv.en_US
dc.identifier.urihttps://doi.org/10.1101%2F2021.06.28.21259529
dc.identifier.urihttp://hdl.handle.net/123456789/1179
dc.language.isoenen_US
dc.publisherNational Institutes of Healthen_US
dc.subjectSARS-COV-2en_US
dc.subjectCOVID-19en_US
dc.subjectGenetic variationen_US
dc.titleImpact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.en_US
dc.typeArticleen_US

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