Abstract
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 × 10−7; empirical p < 1 × 10−5; λS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 × 10−5; empirical p < 1 × 10−4; λS = 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.
Highlights
Ninety percent of clinical visceral leishmaniasis (VL) cases caused by protozoa of the L. donovani species complex (L. donovani, L. archibaldi, L. infantum, and L. chagasi) occur in three foci in India/Bangladesh/Nepal, Sudan, and Brazil
We report on a second genome-wide scan undertaken in two villages occupied by the related Masalit ethnic group in eastern Sudan, in which we provide evidence for major loci at 1p22 and 6q27 that are Y chromosome–lineage and village-specific
Primary Genome Scan In their study, Bucheton et al [13] used 63 multicase families from members of the Aringa ethnic group living in Barbar El Fugura, Gedaref State, eastern Sudan (Figure 1)
Summary
Ninety percent of clinical visceral leishmaniasis (VL) cases caused by protozoa of the L. donovani species complex (L. donovani, L. archibaldi, L. infantum, and L. chagasi) occur in three foci in India/Bangladesh/Nepal, Sudan, and Brazil. In Sudan, familial clustering and marked differences in incidence of clinical disease and skintest reactivity between villages inhabited by different ethnic groups that share environment and exposure [7,8] support a contribution of host genotype to susceptibility. A genome-wide scan recently undertaken in eastern Sudan by Bucheton et al [13] reported a major gene (LOD score 3.5; p 1⁄4 3 3 10À5) on Chromosome 22q12 controlling VL in the Aringa ethnic group. We report on a second genome-wide scan undertaken in two villages occupied by the related Masalit ethnic group in eastern Sudan, in which we provide evidence for major loci at 1p22 and 6q27 that are Y chromosome–lineage and village-specific
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