genome-wide identification of susceptibility alleles for viral infections through a population genetics approach全基因组鉴定病毒感染的易感性的等位基因在群体遗传学方法.pdfVIP

Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach 1,2 1 1 3 1,3 Matteo Fumagalli , Uberto Pozzoli , Rachele Cagliani , Giacomo P. Comi , Nereo Bresolin , Mario 4,5. 1 . Clerici , Manuela Sironi * 1 Scientific Institute IRCCS E. Medea, Bioinformatic Lab, Bosisio Parini (LC), Italy, 2 Bioengineering Department, Politecnico di Milano, Milan, Italy, 3 Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Milan, Italy, 4 Department of Biomedical sciences and Technologies LITA Segrate, University of Milan, Milan, Italy, 5 Don C. Gnocchi ONLUS Foundation IRCCS, Milan, Italy 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