Journal article
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
eLife, Vol.2(0), pp.e01123-e01123
2013
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.
Details
- Title
- A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
- Authors/Creators
- I. Bartha (Author/Creator) - École Polytechnique Fédérale de LausanneJ.M. Carlson (Author/Creator) - Microsoft (United States)C.J. Brumme (Author/Creator) - AIDS VancouverP.J. McLaren (Author/Creator)Z.L. Brumme (Author/Creator) - Simon Fraser UniversityM. John (Author/Creator) - Murdoch UniversityD.W. Haas (Author/Creator) - Vanderbilt University Medical CenterJ. Martinez-Picado (Author/Creator) - Institut d'Investigació en Ciències de la Salut Germans Trias i PujolJ. Dalmau (Author/Creator) - Institut d'Investigació en Ciències de la Salut Germans Trias i PujolC. Lopez-Galindez (Author/Creator) - Instituto de Salud Carlos IIIC. Casado (Author/Creator) - Instituto de Salud Carlos IIIA. Rauch (Author/Creator) - University Hospital of BernH.F. Günthard (Author/Creator) - University Hospital of ZurichE. Bernasconi (Author/Creator) - Ospedale regionale di LuganoP. Vernazza (Author/Creator) - University of St.GallenT. Klimkait (Author/Creator) - Department of Biomedicine BaselS. Yerly (Author/Creator) - Laboratory of Virology, Geneva University Hospitals, Geneva, SwitzerlandS.J. O'Brien (Author/Creator) - Theodosius Dobzhansky Center for Genome Bioinformatics; St. Petersburg State University; St. Petersburg RussiaJ. Listgarten (Author/Creator) - Microsoft (United States)N. Pfeifer (Author/Creator) - Microsoft (United States)C. Lippert (Author/Creator)N. Fusi (Author/Creator) - Microsoft (United States)Z. Kutalik (Author/Creator) - SIB Swiss Institute of BioinformaticsT.M. Allen (Author/Creator) - Ragon Institute of MGH, MIT and HarvardV. Muller (Author/Creator) - Hungarian Academy of SciencesP.R. Harrigan (Author/Creator) - University of British ColumbiaD. Heckerman (Author/Creator) - Microsoft (Canada)A. Telenti (Author/Creator) - University of LausanneJ. Fellay (Author/Creator) - University of Lausanne
- Publication Details
- eLife, Vol.2(0), pp.e01123-e01123
- Publisher
- eLife Sciences Publications
- Identifiers
- 991005541088607891
- Copyright
- 2013 Bartha et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Biology
- ESI research areas
- Biology & Biochemistry