Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis
Journal of Experimental Medicine, Volume 206, No. 12, Year 2009
Notification
URL copied to clipboard!
Description
Approximately 20% of persons living in areas hyperendemic for tuberculosis (TB) display persistent lack of tuberculin skin test (TST) reactivity and appear to be naturally resistant to infection by Mycobacterium tuberculosis. Among those with a positive response, the intensity of TST reactivity varies greatly. The genetic basis of TST reactivity is not known. We report on a genome-wide linkage search for loci that have an impact on TST reactivity, which is defined either as zero versus nonzero (TST-BINa) or as extent of TST in millimeters (TST-quantitative trait locus [QTL]) in a panel of 128 families, including 350 siblings, from an area of South Africa hyperendemic for TB. We detected a major locus (TST1) on chromosomal region 11p14 (P = 1.4 x 10-5), which controls TST-BINa, with a lack of responsiveness indicating T cell-independent resistance to M. tuberculosis. We also detected a second major locus ( TST2 ) on chromosomal region 5p15 (P < 10-5), which controls TST-QTL or the intensity of T cell-mediated delayed type hypersensitivity (DTH) to tuberculin. Fine mapping of this region identified SLC6A3, encoding the dopamine transporter DAT1, as a promising gene for further studies. Our results pave the way for the understanding of the molecular mechanisms involved in resistance to M. tuberculosis infection in endemic areas (TST1) and for the identification of critical regulators of T cell-dependent DTH to tuberculin (TST2). © 2009 Cobat et al.
Authors & Co-Authors
Cobat, Aurélie
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Gallant, Caroline Julie
Canada, Montreal
Université Mcgill
Simkin, Leah
Canada, Montreal
Université Mcgill
Black, Gillian Frances
South Africa, Stellenbosch
Stellenbosch University
Stanley, Kim
South Africa, Stellenbosch
Stellenbosch University
Hughes, Jane E.
South Africa, Cape Town
University of Cape Town
Doherty, Timothy Mark
Denmark, Copenhagen
Statens Serum Institut
Hanekom, Willem Albert
South Africa, Cape Town
University of Cape Town
Eley, Brian S.
South Africa, Cape Town
University of Cape Town
Jaïs, Jean Philippe
France, Paris
Université Paris Cité
Boland, Anne
France, Evry
Centre National de Recherche en Génomique Humaine
Van Helden, Paul D.
South Africa, Stellenbosch
Stellenbosch University
Casanova, Jean Laurent
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
United States, New York
Rockefeller University
Abel, Laurent
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
United States, New York
Rockefeller University
Hoal, Eileen G.
South Africa, Stellenbosch
Stellenbosch University
Schurr, Erwin
Canada, Montreal
Université Mcgill
Alcaïs, Alexandre
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
United States, New York
Rockefeller University
Statistics
Citations: 149
Authors: 17
Affiliations: 8
Identifiers
Doi:
10.1084/jem.20090892
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Genetics And Genomics
Infectious Diseases
Study Approach
Quantitative
Study Locations
South Africa