Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil.
A genome-wide scan was conducted for visceral leishmaniasis (VL) in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected). Non-parametric multipoint analysis detected nine chromosomal regions with provisional evidence (logarithm of the odds (LOD) scores 0.95-1.66; 0.003<P<0.018) for linkage. To confirm linkage, 132 individuals (43 affected) from 19 independently ascertained families were genotyped across these regions. Three regions (6q27, 7q11.22 and 17q11.2-q21.3) retained evidence (LOD scores 1.08, 1.34, 1.14; P=0.013, 0.007, 0.011) for linkage. To determine which genes contribute to linkage at 17q11.2-q21.3, 80 single nucleotide polymorphisms were genotyped in 98 nuclear families with 183 affected individuals. Family-based association test analysis indicated associations at two chemokine genes, CCL1 and CCL16, that lie 1.6 Mb apart, show some extended linkage disequilibrium with each other, but each lie within different clusters of candidate CCL genes. Multiple genes may therefore contribute to the linkage peak for VL at 17q12.
Jamieson
S E
SE
Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
Miller
E N
EN
Peacock
C S
CS
Fakiola
M
M
Wilson
M E
ME
Bales-Holst
A
A
Shaw
M-A
MA
Silveira
F
F
Shaw
J J
JJ
Jeronimo
S M
SM
Blackwell
J M
JM
D001938:Brazil; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide
C065971:CCL1 protein, human; C481939:CCL16 protein, human; D054402:Chemokine CCL1; D019742:Chemokines, CC