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Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians.
Genes Immun 2004; 5(1):46-57GI

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-1alpha, CCL4/MIP-1beta, 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 (Z(lr) score 2.34; P=0.01) and D17S1795 (Z(lr) 2.67; P=0.004) and a single peak for tuberculosis at D17S250 (Z(lr) 2.04; P=0.02). Combined analysis shows significant linkage (peak Z(lr) 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.

Authors+Show Affiliations

Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14735149

Citation

Jamieson, S E., et al. "Evidence for a Cluster of Genes On Chromosome 17q11-q21 Controlling Susceptibility to Tuberculosis and Leprosy in Brazilians." Genes and Immunity, vol. 5, no. 1, 2004, pp. 46-57.
Jamieson SE, Miller EN, Black GF, et al. Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun. 2004;5(1):46-57.
Jamieson, S. E., Miller, E. N., Black, G. F., Peacock, C. S., Cordell, H. J., Howson, J. M., ... Blackwell, J. M. (2004). Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes and Immunity, 5(1), pp. 46-57.
Jamieson SE, et al. Evidence for a Cluster of Genes On Chromosome 17q11-q21 Controlling Susceptibility to Tuberculosis and Leprosy in Brazilians. Genes Immun. 2004;5(1):46-57. PubMed PMID: 14735149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. AU - Jamieson,S E, AU - Miller,E N, AU - Black,G F, AU - Peacock,C S, AU - Cordell,H J, AU - Howson,J M M, AU - Shaw,M-A, AU - Burgner,D, AU - Xu,W, AU - Lins-Lainson,Z, AU - Shaw,J J, AU - Ramos,F, AU - Silveira,F, AU - Blackwell,J M, PY - 2004/1/22/pubmed PY - 2004/9/29/medline PY - 2004/1/22/entrez SP - 46 EP - 57 JF - Genes and immunity JO - Genes Immun. VL - 5 IS - 1 N2 - 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-1alpha, CCL4/MIP-1beta, 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 (Z(lr) score 2.34; P=0.01) and D17S1795 (Z(lr) 2.67; P=0.004) and a single peak for tuberculosis at D17S250 (Z(lr) 2.04; P=0.02). Combined analysis shows significant linkage (peak Z(lr) 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. SN - 1466-4879 UR - https://www.unboundmedicine.com/medline/citation/14735149/Evidence_for_a_cluster_of_genes_on_chromosome_17q11_q21_controlling_susceptibility_to_tuberculosis_and_leprosy_in_Brazilians_ L2 - http://dx.doi.org/10.1038/sj.gene.6364029 DB - PRIME DP - Unbound Medicine ER -