The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility
- PMID: 15637236
- DOI: 10.1126/science.1101160
The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility
Abstract
Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.
Comment in
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HIV/AIDS. HIV: experiencing the pressures of modern life.Science. 2005 Mar 4;307(5714):1422-4. doi: 10.1126/science.1110009. Science. 2005. PMID: 15746416 No abstract available.
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