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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 ; λ S  = 5.1) and 6q27 (LOD score 3.74; nominal  p  = 1.68 × 10 −5 ; empirical  p  < 1 × 10 −4 ; λ S  = 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.

Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan