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The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Open accessAbstract
Getting HIV Under Control: Approximately 1 in 300 people infected with HIV are HIV “controllers” who are able to maintain long-term control of the virus without medication and who do not progress to AIDS. Uncovering the genetic basis for this ability is of great interest. Pereyra et al. (p. 1551 , published online 4 November; see the Perspective by McMichael and Jones ) now present genome-wide association results from patients enrolled in the International HIV Controllers Study. The analysis compared HIV controllers of European, African-American, and Hispanic descent with HIV progressors and found >300 variants that reached genome-wide significance, all of which were in the major histocompatibility class I (HLA) region on chromosome 6. Analysis of the effects of individual amino acids within classical HLA proteins revealed six independently significant residues, five of which lined the peptide-binding groove. Thus, differences in binding to viral peptide antigens by HLA may be the major factors underlying genetic differences between HIV controllers and progressors.
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A note on a general definition of the coefficient of determination
NAGELKERKE, N. J. D. (1991) · Biometrika · doi:10.1093/biomet/78.3.691 · Cited by 5,927
Integrating common and rare genetic variation in diverse human populations
The International HapMap 3 Consortium (2010) · Nature · doi:10.1038/nature09298 · Cited by 3,026
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Cited by
Genome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., et al. (2018) · Science · doi:10.1126/science.aao4572 · Cited by 1,142
The MHC locus and genetic susceptibility to autoimmune and infectious diseases
Matzaraki, V., Kumar, V., Wijmenga, C., & Zhernakova, A. (2017) · Genome biology · doi:10.1186/s13059-017-1207-1 · Cited by 566
Fairfax, B. P., Makino, S., Radhakrishnan, J., Plant, K., Leslie, S., Dilthey, A., Ellis, P., Langford, C., Vannberg, F. O., & Knight, J. C. (2012) · Nature Genetics · doi:10.1038/ng.2205 · Cited by 486
Exome sequencing and the genetic basis of complex traits
Kiezun, A., Garimella, K., Do, R., Stitziel, N. O., Neale, B. M., McLaren, P. J., Gupta, N., Sklar, P., Sullivan, P. F., Moran, J. L., et al. (2012) · Nature Genetics · doi:10.1038/ng.2303 · Cited by 372
Metadata
- Authors
- Study, T. I. H. C.
- Venue
- Science
- Published
- 2010-12-10
- Volume
- 330
- Issue
- 6010
- Pages
- 1551-1557
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2109130469
- Cited by
- 1,171
- References
- 3
- FWCI
- 38.20
- Type
- journal article
- Language
- en
- Open access
- green
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