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 1.72 107;
empirical p < 1 105; S 5.1) and 6q27 (LOD score 3.74; nominal p 1.68 105; empirical p < 1 104; S 2.3) that were Y chromosomelineage 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.