TY - JOUR
KW - Animals
KW - Brazil
KW - Case-Control Studies
KW - Chemokine CCL3
KW - Chemokine CCL4
KW - Chemokines, CC
KW - Chromosomes, Human, Pair 17
KW - DNA-Binding Proteins
KW - Female
KW - Gene Frequency
KW - Genetic Markers
KW - Genetic Predisposition to Disease
KW - Genetic Testing
KW - genotype
KW - Humans
KW - leprosy
KW - Macrophage Inflammatory Proteins
KW - Male
KW - Mice
KW - Milk Proteins
KW - Multigene Family
KW - Point Mutation
KW - Proteins
KW - STAT5 Transcription Factor
KW - Trans-Activators
KW - Tuberculosis
KW - Tumor Suppressor Proteins
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
AB - <p>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.</p>
BT - Genes and immunity
C1 - http://www.ncbi.nlm.nih.gov/pubmed/14735149?dopt=Abstract
CN - JAMIESON 2004
DA - 2004 Jan
DO - 10.1038/sj.gene.6364029
IS - 1
J2 - Genes Immun.
LA - eng
N2 - <p>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.</p>
PY - 2004
SP - 46
EP - 57
T2 - Genes and immunity
TI - Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians.
UR - Evidence for a cluster of genes on chromosome 
VL - 5
SN - 1466-4879
ER -