A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
Elife
; 2: e01123, 2013 Oct 29.
Article
en En
| MEDLINE
| ID: mdl-24171102
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. DOIhttp//dx.doi.org/10.7554/eLife.01123.001.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Infecciones por VIH
/
VIH-1
/
Genoma Viral
/
Carga Viral
/
Polimorfismo de Nucleótido Simple
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza