title: 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.
authors.affiliation: 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.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Hector
authors.initials: H
authors.lastname: Bolivar
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.forename: Racquel
authors.initials: R
authors.lastname: Sanchez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Catano
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Marlon P
authors.initials: MP
authors.lastname: Quinones
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Murthy
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.forename: William
authors.initials: W
authors.lastname: Bradley
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'connell
authors.forename: Brian K
authors.initials: BK
authors.lastname: Agan
authors.forename: Seema S
authors.initials: SS
authors.lastname: Ahuja
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D002679:Pan troglodytes / Q000235:genetics; D010641:Phenotype; D011634:Public Health; D044469:Racial Groups / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: C492767:CCL3L1 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5