Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan.
Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 x 10(-7); empirical p < 1 x 10(-5); lambdaS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambdaS = 2.3) that were Y chromosome-lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.
Miller
E Nancy
EN
Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
Fadl
Manal
M
Mohamed
Hiba S
HS
Elzein
Abier
A
Jamieson
Sarra E
SE
Cordell
Heather J
HJ
Peacock
Christopher S
CS
Fakiola
Michaela
M
Raju
Madhuri
M
Khalil
Eltahir A
EA
Elhassan
Ahmed
A
Musa
Ahmed M
AM
Ibrahim
Muntaser E
ME
Blackwell
Jenefer M
JM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D003241:Consanguinity; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D012423:Rural Health; D012424:Rural Population; D013045:Species Specificity; D013397:Sudan
D004272:DNA, Mitochondrial