Genome-wide identification of susceptibility alleles for viral infections through a population genetics approach.
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.
Fumagalli
Matteo
M
Scientific Institute IRCCS E. Medea, Bioinformatic Lab, Bosisio Parini (LC), Italy.
Pozzoli
Uberto
U
Cagliani
Rachele
R
Comi
Giacomo P
GP
Bresolin
Nereo
N
Clerici
Mario
M
Sironi
Manuela
M
D000483:Alleles; D053263:Gene Regulatory Networks / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012641:Selection, Genetic; D014777:Virus Diseases / Q000235:genetics*; D014780:Viruses / Q000235:genetics