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 Sen; Matthew J. Dolan; Sunil K. Ahuja

doi:10.1126/science.1101160

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

971 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 language	English
Pages (from-to)	1434-1440
Number of pages	7
Journal	Science
Volume	307
Issue number	5714
DOIs	https://doi.org/10.1126/science.1101160
State	Published - 4 Mar 2005
Externally published	Yes

Access to Document

10.1126/science.1101160

Cite this

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

@article{0ba0a4d7ec194854aab63ff397c74a5f,

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-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.",

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

year = "2005",

month = mar,

day = "4",

doi = "10.1126/science.1101160",

language = "English",

volume = "307",

pages = "1434--1440",

journal = "Science",

issn = "0036-8075",

number = "5714",

}

Gonzalez, E, Kulkarni, H, Bolivar, H, Mangano, A, Sanchez, R, Catano, G, Nibbs, RJ, Freedman, BI, Quinones, MP, Bamshad, MJ, Murthy, KK, Rovin, BH, Bradley, W, Clark, RA, Anderson, SA, O'Connell, RJ , Agan, BK, Ahuja, SS, Bologna, R, Sen, L, Dolan, MJ & Ahuja, SK 2005, 'The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility', Science, vol. 307, no. 5714, pp. 1434-1440. https://doi.org/10.1126/science.1101160

TY - JOUR

T1 - The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility

AU - Gonzalez, Enrique

AU - Kulkarni, Hemant

AU - Bolivar, Hector

AU - Mangano, Andrea

AU - Sanchez, Racquel

AU - Catano, Gabriel

AU - Nibbs, Robert J.

AU - Freedman, Barry I.

AU - Quinones, Marlon P.

AU - Bamshad, Michael J.

AU - Murthy, Krishna K.

AU - Rovin, Brad H.

AU - Bradley, William

AU - Clark, Robert A.

AU - Anderson, Stephanie A.

AU - O'Connell, Robert J.

AU - Agan, Brian K.

AU - Ahuja, Seema S.

AU - Bologna, Rosa

AU - Sen, Luisa

AU - Dolan, Matthew J.

AU - Ahuja, Sunil K.

PY - 2005/3/4

Y1 - 2005/3/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=20044377204&partnerID=8YFLogxK

U2 - 10.1126/science.1101160

DO - 10.1126/science.1101160

M3 - Article

C2 - 15637236

AN - SCOPUS:20044377204

SN - 0036-8075

VL - 307

SP - 1434

EP - 1440

JO - Science

JF - Science

IS - 5714

ER -

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

Abstract

Access to Document

Fingerprint

Cite this