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dc.contributor.authorAndersen, Kristian G
dc.contributor.authorShylakhter, Ilya
dc.contributor.authorTabrizi, Shervin
dc.contributor.authorGrossman, Sharon Rachel
dc.contributor.authorHappi, Christian Tientcha
dc.contributor.authorSabeti, Pardis Christine
dc.date.accessioned2013-11-01T16:56:48Z
dc.date.issued2012
dc.identifier.citationAndersen, Kristian G., Ilya Shylakhter, Shervin Tabrizi, Sharon R. Grossman, Christian T. Happi, and Pardis C. Sabeti. 2012. Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever. Philosophical Transactions of the Royal Society B: Biological Sciences 367(1590): 868-877.en_US
dc.identifier.issn0962-8436en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11248782
dc.description.abstractRapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 (IL21), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21. Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit.en_US
dc.description.sponsorshipOrganismic and Evolutionary Biologyen_US
dc.language.isoen_USen_US
dc.publisherThe Royal Societyen_US
dc.relation.isversionofdoi:10.1098/rstb.2011.0299en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267117/pdf/en_US
dash.licenseLAA
dc.subjectLassa feveren_US
dc.subjectnatural selectionen_US
dc.subjectpositive selectionen_US
dc.subjectgenome-wide scansen_US
dc.subjectinterleukin 21en_US
dc.subjectLARGEen_US
dc.titleGenome-Wide Scans Provide Evidence for Positive Selection of Genes Implicated in Lassa Feveren_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPhilosophical Transactions of the Royal Society B: Biological Sciencesen_US
dash.depositing.authorSabeti, Pardis Christine
dc.date.available2013-11-01T16:56:48Z
dc.identifier.doi10.1098/rstb.2011.0299*
dash.contributor.affiliatedTabrizi, Shervin
dash.contributor.affiliatedGrossman, Sharon
dash.contributor.affiliatedAndersen, Kristian G
dash.contributor.affiliatedHappi, Christian
dash.contributor.affiliatedSabeti, Pardis


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