RATIONALE: Tuberculosis remains a major cause of morbidity and mortality in the developing world. A better understanding of the mechanisms of disease protection could allow novel strategies to disease management and control. OBJECTIVES: To identify human genomic loci with evidence of linkage to tuberculosis susceptibility and, within these loci, to identify individual genes influencing tuberculosis susceptibility. METHODS: Affected sibling pair analysis in South African and Malawian populations. Independent case-control study in West Africa. MEASUREMENTS AND MAIN RESULTS: Two novel putative loci for tuberculosis susceptibility are identified: chromosome 6p21-q23 and chromosome 20q13.31-33--the latter with the strongest evidence for any locus reported to date in human tuberculosis (single point LOD score of 3.1, P = 10(-4), with a maximum likelihood score [MLS] of 2.8). An independent, multistage genetic association study in West African populations mapped this latter region in detail, finding evidence that variation in the melanocortin 3 receptor (MC3R) and cathepsin Z (CTSZ) genes play a role in the pathogenesis of tuberculosis. CONCLUSIONS: These results demonstrate how a genomewide approach to the complex phenotype of human tuberculosis can identify novel targets for further research.
RATIONALE: Tuberculosis remains a major cause of morbidity and mortality in the developing world. A better understanding of the mechanisms of disease protection could allow novel strategies to disease management and control. OBJECTIVES: To identify human genomic loci with evidence of linkage to tuberculosis susceptibility and, within these loci, to identify individual genes influencing tuberculosis susceptibility. METHODS: Affected sibling pair analysis in South African and Malawian populations. Independent case-control study in West Africa. MEASUREMENTS AND MAIN RESULTS: Two novel putative loci for tuberculosis susceptibility are identified: chromosome 6p21-q23 and chromosome 20q13.31-33--the latter with the strongest evidence for any locus reported to date in humantuberculosis (single point LOD score of 3.1, P = 10(-4), with a maximum likelihood score [MLS] of 2.8). An independent, multistage genetic association study in West African populations mapped this latter region in detail, finding evidence that variation in the melanocortin 3 receptor (MC3R) and cathepsin Z (CTSZ) genes play a role in the pathogenesis of tuberculosis. CONCLUSIONS: These results demonstrate how a genomewide approach to the complex phenotype of humantuberculosis can identify novel targets for further research.
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Authors: J Satsangi; M Parkes; E Louis; L Hashimoto; N Kato; K Welsh; J D Terwilliger; G M Lathrop; J I Bell; D P Jewell Journal: Nat Genet Date: 1996-10 Impact factor: 38.330
Authors: Chiea C Khor; Stephen J Chapman; Fredrik O Vannberg; Aisling Dunne; Caroline Murphy; Edmund Y Ling; Angela J Frodsham; Andrew J Walley; Otto Kyrieleis; Amir Khan; Christophe Aucan; Shelley Segal; Catrin E Moore; Kyle Knox; Sarah J Campbell; Christian Lienhardt; Anthony Scott; Peter Aaby; Oumou Y Sow; Robert T Grignani; Jackson Sillah; Giorgio Sirugo; Nobert Peshu; Thomas N Williams; Kathryn Maitland; Robert J O Davies; Dominic P Kwiatkowski; Nicholas P Day; Djamel Yala; Derrick W Crook; Kevin Marsh; James A Berkley; Luke A J O'Neill; Adrian V S Hill Journal: Nat Genet Date: 2007-02-25 Impact factor: 38.330
Authors: Byung Lae Park; Lyoung Hyo Kim; Suhg Namgoong; Ji On Kim; Jason Yongha Kim; Hun Soo Chang; Jong Sook Park; An Soo Jang; Sung Woo Park; Do Jin Kim; Ki Up Kim; Yang Gee Kim; Soo-Taek Uh; Ki Hyun Seo; Young Hoon Kim; Choon Sik Park; Hyoung Doo Shin Journal: Lung Date: 2014-07-27 Impact factor: 2.584
Authors: Lindsey A Adams; Marlo Möller; Almut Nebel; Stefan Schreiber; Lize van der Merwe; Paul D van Helden; Eileen G Hoal Journal: Eur J Hum Genet Date: 2011-02-02 Impact factor: 4.246
Authors: Allison R Baker; Sarah Zalwango; LaShaunda L Malone; Robert P Igo; Feiyou Qiu; Mary Nsereko; Mark D Adams; Pamela Supelak; Harriet Mayanja-Kizza; W Henry Boom; Catherine M Stein Journal: Hum Immunol Date: 2011-02-25 Impact factor: 2.850