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Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians

Genes & Immunity volume 5, pages 46–57 (2004)Cite this article

Abstract

The region of conserved synteny on mouse chromosome 11/human 17q11–q21 is known to carry a susceptibility gene(s) for intramacrophage pathogens. The region is rich in candidates including NOS2A, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCR7, STAT3 and STAT5A/5B. To examine the region in man, we studied 92 multicase tuberculosis (627 individuals) and 72 multicase leprosy (372 individuals) families from Brazil. Multipoint nonparametric analysis (ALLEGRO) using 16 microsatellites shows two peaks of linkage for leprosy at D17S250 (Zlr score 2.34; P=0.01) and D17S1795 (Zlr 2.67; P=0.004) and a single peak for tuberculosis at D17S250 (Zlr 2.04; P=0.02). Combined analysis shows significant linkage (peak Zlr 3.38) at D17S250, equivalent to an allele sharing LOD score 2.48 (P=0.0004). To determine whether one or multiple genes contribute, 49 informative single nucleotide polymorphisms were typed in candidate genes. Family-based allelic association testing that was robust to family clustering demonstrated significant associations with tuberculosis susceptibility at four loci separated by intervals (NOS2A–8.4 Mb–CCL18–32.3 kb–CCL4–6.04 Mb–STAT5B) up to several Mb. Stepwise conditional logistic regression analysis using a case/pseudo-control data set showed that the four genes contributed separate main effects, consistent with a cluster of susceptibility genes across 17q11.2.

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Acknowledgements

This work was funded by grants from the Wellcome Trust. SJ held an MRC research studentship. We thank the people of Belem for their cooperation in this study.

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Author notes

  1. D Burgner

    Present address: Princess Margaret Hospital, Subiaco, Western Australia, Australia

  2. J J Shaw

    Present address: Department of Parasitology, Institute of Biomedical Sciences, Sao Paulo University, 05508-900, Brazil

Authors and Affiliations

  1. Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK

    S E Jamieson, E N Miller, G F Black, C S Peacock, H J Cordell, J M M Howson & J M Blackwell

  2. Department of Biology, University of Leeds, Leeds, UK

    M-A Shaw

  3. The Wellcome Trust Centre for Human Genetics, Oxford, UK

    D Burgner

  4. Wolfson Institute for Biomedical Research, Rayne Institute, University College, London, UK

    W Xu

  5. Instituto Evandro Chagas, Belem, Brazil

    Z Lins-Lainson, J J Shaw, F Ramos & F Silveira

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  1. S E Jamieson
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Correspondence to J M Blackwell.

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Jamieson, S., Miller, E., Black, G. et al. Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun 5, 46–57 (2004). https://doi.org/10.1038/sj.gene.6364029

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