The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility

Enrique Gonzalez, Hemant Kulkarni, Hector Bolivar, Andrea Mangano, Racquel Sanchez, Gabriel Catano, Robert J. Nibbs, Barry I. Freedman, Marlon P. Quinones, Michael J. Bamshad, Krishna K. Murthy, Brad H. Rovin, William Bradley, Robert A. Clark, Stephanie A. Anderson, Robert J. O'Connell, Brian K. Agan, Seema S. Ahuja, Rosa Bologna, Luisa SenMatthew J. Dolan, Sunil K. Ahuja

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908 Scopus citations

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-1αP), 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.

Original languageEnglish (US)
Pages (from-to)1434-1440
Number of pages7
JournalScience
Volume307
Issue number5714
DOIs
StatePublished - Mar 4 2005

ASJC Scopus subject areas

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    Gonzalez, E., Kulkarni, H., Bolivar, H., Mangano, A., Sanchez, R., Catano, G., Nibbs, R. J., Freedman, B. I., Quinones, M. P., Bamshad, M. J., Murthy, K. K., Rovin, B. H., Bradley, W., Clark, R. A., Anderson, S. A., O'Connell, R. J., Agan, B. K., Ahuja, S. S., Bologna, R., ... Ahuja, S. K. (2005). The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science, 307(5714), 1434-1440. https://doi.org/10.1126/science.1101160