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


Autoria(s): Bartha I.; Carlson J.M.; Brumme C.J.; McLaren P.J.; Brumme Z.L.; John M.; Haas D.W.; Martinez-Picado J.; Dalmau J.; López-Galíndez 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.; Müller V.; Harrigan P.R.; Heckerman D.; Telenti A.; Fellay J.
Data(s)

2013

Resumo

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. DOI:http://dx.doi.org/10.7554/eLife.01123.001.

Identificador

http://serval.unil.ch/?id=serval:BIB_AD72A6E486EC

isbn:2050-084X (Electronic)

pmid:24171102

doi:10.7554/eLife.01123

isiid:000328638400001

http://my.unil.ch/serval/document/BIB_AD72A6E486EC.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_AD72A6E486EC4

Idioma(s)

en

Direitos

info:eu-repo/semantics/openAccess

Fonte

eLIFE, vol. 2, pp. e01123

Tipo

info:eu-repo/semantics/article

article