Publication Date:
2005-01-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez, Enrique -- Kulkarni, Hemant -- Bolivar, Hector -- Mangano, Andrea -- Sanchez, Racquel -- Catano, Gabriel -- Nibbs, Robert J -- Freedman, Barry I -- Quinones, Marlon P -- Bamshad, Michael J -- Murthy, Krishna K -- Rovin, Brad H -- Bradley, William -- Clark, Robert A -- Anderson, Stephanie A -- O'connell, Robert J -- Agan, Brian K -- Ahuja, Seema S -- Bologna, Rosa -- Sen, Luisa -- Dolan, Matthew J -- Ahuja, Sunil K -- AI043279/AI/NIAID NIH HHS/ -- AI046326/AI/NIAID NIH HHS/ -- MH069270/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 4;307(5714):1434-40. Epub 2005 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, and Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15637236" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Aged
;
Animals
;
Chemokines, CC/*genetics/metabolism
;
Child
;
Cohort Studies
;
Continental Population Groups/genetics
;
Disease Progression
;
Ethnic Groups/genetics
;
Female
;
*Gene Dosage
;
*Gene Duplication
;
*Genetic Predisposition to Disease
;
Genotype
;
HIV Infections/epidemiology/*genetics/*immunology/virology
;
*HIV-1/metabolism
;
Humans
;
Male
;
Middle Aged
;
Pan troglodytes/genetics
;
Phenotype
;
Public Health
;
Receptors, CCR5/genetics/metabolism
;
Selection, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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