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Abstract Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results: Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions: These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.

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Autor(es)

McLaren, Paul J -  Pulit, Sara L -  Gurdasani, Deepti -  Bartha, Istvan -  Shea, Patrick R -  Pomilla, Cristina -  Gupta, Namrata -  Gkrania -  Klotsas, Effrossyni -  Young, Elizabeth H -  Bannert, Norbert -  Del Amo, Julia -  Gill, M John -  Gilmour, Jill -  Kellam, Paul -  Kelleher, Anthony D -  Sönnerborg, Anders -  Zangerle, Robert -  Post, Frank A -  Fisher, Martin -  Haas, David W -  Walker, Bruce D -  Porter, Kholoud -  Goldstein, David B -  Sandhu, Manjinder S -  de Bakker, Paul I W -  Fellay, Jacques - 

Id.: 71228386

Idioma: inglés (Estados Unidos)  - 

Versión: 1.0

Estado: Final

Palabras claveHIV/AIDS - 

Tipo de recurso: Journal Article  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: open

Requerimientos técnicos:  Browser: Any - 

Relación: [References] doi:10.1093/infdis/jix470
[References] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853944/pdf/
[References] The Journal of Infectious Diseases

Fecha de contribución: 21-abr-2018

Contacto:

Localización:
* McLaren, P. J., S. L. Pulit, D. Gurdasani, I. Bartha, P. R. Shea, C. Pomilla, N. Gupta, et al. 2017. “Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.” The Journal of Infectious Diseases 216 (9): 1063-1069. doi:10.1093/infdis/jix470. http://dx.doi.org/10.1093/infdis/jix470.

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