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A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

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Item Type:Article
Title:A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
Creators Name:Bartha, I. and Carlson, J.M. and Brumme, C.J. and McLaren, P.J. and Brumme, Z.L. and John, M. and Haas, D.W. and Martinez-Picado, J. and Dalmau, J. and López-Galíndez, C. and Casado, C. and Rauch, A. and Günthard, H.F. and Bernasconi, E. and Vernazza, P. and Klimkait, T. and Yerly, S. and O'Brien, S.J. and Listgarten, J. and Pfeifer, N. and Lippert, C. and Fusi, N. and Kutalik, Z. and Allen, T.M. and Müller, V. and Harrigan, P.R. and Heckerman, D. and Telenti, A. and Fellay, J.
Abstract:HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction.
Keywords:Alleles, Genome-Wide Association Study, HIV Infections, HIV-1, Histocompatibility Antigens Class I, Host-Pathogen Interactions, Human Genome, Single Nucleotide Polymorphism, Viral Genome, Viral Load
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications (U.K.)
Volume:2
Page Range:e01123
Date:29 October 2013
Official Publication:https://doi.org/10.7554/eLife.01123
PubMed:View item in PubMed

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