Viruses Helped Shape Human Genetic Variability
ScienceDaily (Feb. 19, 2010) — Viruses have played a role in shaping human genetic variability, according to a study published February 19 in the open-access journal PLoS Genetics. The researchers, from the Don C. Gnocchi and Eugenio Medea Scientific Institutes, the University of Milan and the Politecnico di Milano, Italy, used population genetics approaches to identify gene variants that augment susceptibility to viral infections or protect from such infections.
New research shows that viruses have played a role in shaping human genetic variability.
(Credit: iStockphoto/Sebastian Kaulitzki)
Viruses have represented a threat to human populations throughout history and still account for a large proportion of disease and death worldwide. The identification of gene variants that modulate the susceptibility to viral infections is thus central to the development of novel therapeutic approaches and vaccines. Due to the long relationship between humans and viruses, gene variants conferring increased resistance to these pathogens have likely been targeted by natural selection. This concept was exploited to identify variants in the human genome that modulate susceptibility to infection or the severity of the ensuing disease.
...
Read more here/Leia mais aqui: Science Daily
+++++
Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach
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 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.
Author Summary Top
Viruses have represented a constant threat to human communities throughout their history, therefore, human genes involved in anti-viral response can be thought of as targets of virus-driven selective pressure. Here we utilized the marks left by selection to identify viral infection-associated allelic variants. We analyzed more than 660,000 single nucleotide polymorphisms (SNPs) genotyped in 52 human populations, and we used virus diversity (the number of different viruses in a geographic region) to measure virus-driven selective pressure. Results showed that genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors display more variants associated with virus diversity than expected by chance. The same holds true for genes encoding proteins that directly interact with viral components. Genome-wide analysis identified 441 variants, mapping to 139 human genes, significantly associated with virus-diversity. We analyzed the functional relationships among genes subjected to virus-driven selective pressure and identified a complex interaction network enriched in viral products-interacting proteins. Therefore, we describe a novel approach for the identification of gene variants that may be involved in the susceptibility to viral infections.
Citation: Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Bresolin N, et al. (2010) Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach. PLoS Genet 6(2): e1000849. doi:10.1371/journal.pgen.1000849
Editor: Harmit S. Malik, Fred Hutchinson Cancer Research Center, United States of America
Received: August 24, 2009; Accepted: January 18, 2010; Published: February 19, 2010
Copyright: © 2010 Fumagalli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: MC is supported by grants from Istituto Superiore di Sanita “Programma Nazionale di Ricerca sull” AIDS, the EMPRO and AVIP EC WP6 Projects, the nGIN EC WP7 Project, the Japan Health Science Foundation, 2008 Ricerca Finalizzata [Italian Ministry of Health], 2008 Ricerca Corrente [Italian Ministry of Health], Progetto FIRB RETI: Rete Italiana Chimica Farmaceutica CHEM-PROFARMA-NET [RBPR05NWWC], and Fondazione CARIPLO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: manuela.sironi@bp.lnf.it
# These authors contributed equally to this work.
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.
Author Summary Top
Viruses have represented a constant threat to human communities throughout their history, therefore, human genes involved in anti-viral response can be thought of as targets of virus-driven selective pressure. Here we utilized the marks left by selection to identify viral infection-associated allelic variants. We analyzed more than 660,000 single nucleotide polymorphisms (SNPs) genotyped in 52 human populations, and we used virus diversity (the number of different viruses in a geographic region) to measure virus-driven selective pressure. Results showed that genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors display more variants associated with virus diversity than expected by chance. The same holds true for genes encoding proteins that directly interact with viral components. Genome-wide analysis identified 441 variants, mapping to 139 human genes, significantly associated with virus-diversity. We analyzed the functional relationships among genes subjected to virus-driven selective pressure and identified a complex interaction network enriched in viral products-interacting proteins. Therefore, we describe a novel approach for the identification of gene variants that may be involved in the susceptibility to viral infections.
Citation: Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Bresolin N, et al. (2010) Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach. PLoS Genet 6(2): e1000849. doi:10.1371/journal.pgen.1000849
Editor: Harmit S. Malik, Fred Hutchinson Cancer Research Center, United States of America
Received: August 24, 2009; Accepted: January 18, 2010; Published: February 19, 2010
Copyright: © 2010 Fumagalli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: MC is supported by grants from Istituto Superiore di Sanita “Programma Nazionale di Ricerca sull” AIDS, the EMPRO and AVIP EC WP6 Projects, the nGIN EC WP7 Project, the Japan Health Science Foundation, 2008 Ricerca Finalizzata [Italian Ministry of Health], 2008 Ricerca Corrente [Italian Ministry of Health], Progetto FIRB RETI: Rete Italiana Chimica Farmaceutica CHEM-PROFARMA-NET [RBPR05NWWC], and Fondazione CARIPLO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: manuela.sironi@bp.lnf.it
# These authors contributed equally to this work.
++++
