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Genome-wide identification of susceptibility alleles for viral infections through a population genetics approach.


ABSTRACT: Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.

SUBMITTER: Fumagalli M 

PROVIDER: S-EPMC2824813 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Genome-wide identification of susceptibility alleles for viral infections through a population genetics approach.

Fumagalli Matteo M   Pozzoli Uberto U   Cagliani Rachele R   Comi Giacomo P GP   Bresolin Nereo N   Clerici Mario M   Sironi Manuela M  

PLoS genetics 20100219 2


Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functio  ...[more]

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