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

Bartha, I., Carlson, J.M., Brumme, C.J., McLaren, P.J., Brumme, Z.L., John, M., Haas, D.W., Martinez-Picado, J., Dalmau, J., Lopez-Galindez, C., Casado, C., Rauch, A., Günthard, H.F., Bernasconi, E., Vernazza, P., Klimkait, T., Yerly, S., O'Brien, S.J., Listgarten, J., Pfeifer, N., Lippert, C., Fusi, N., Kutalik, Z., Allen, T.M., Muller, V., Harrigan, P.R., Heckerman, D., Telenti, A. and Fellay, J. (2013) A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife, 2 . e01123-e01123.

Free to read: http://dx.doi.org/10.7554/eLife.01123
*No subscription required

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.

Item Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: eLife Sciences Publications
Copyright: 2013 Bartha et al.
URI: http://researchrepository.murdoch.edu.au/id/eprint/19638
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