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

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.

Genetic Predisposition to Self‐Curing Infection with the ProtozoanLeishmania chagasi:A Genomewide Scan

“…A minor locus (2q22-q23) was also suggestive of linkage in families with negative LOD scores for the 22q12 locus (LOD score, 2.29) [25]. A second genomewide scan of 2 ethnic groups in a nearby region of Sudan not only failed to reproduce the 22q12 linkage peak, but it also described 2 regions with strong linkage to VL at loci 1p22 (LOD score, 5.65) and 6q27 (LOD score, 3.74) that were village-specific and Y chromosome-specific, suggesting significant contributions from distinct founders [26]. A genome scan of VL in multiplex pedigrees from northern Brazil, which included some of our VL families, confirmed the peak at locus 6q27 (LOD, score 1.08) and identified 2 additional regions of interest (7q11.22 and 17q11.2-q21.3; LOD scores, 1.34 and 1.14, respectively).…”

The kiss of death: three tests of the relationship between disease threat and ritualized physical contact within traditional cultures

“…Evidence of the importance of environmental cues in calibrating the immune system to the local pathogen ecology (e.g., Miller et al, 2007) suggest by analogy that relevant facultatively-adjusted behavioral adaptations are indeed possible. Here too, the patterns of behaviors observed may reflect underlying cross-cultural psychological differences, albeit in this case reflecting not differences in genotype, but the impact of differing ecological inputs on phenotype.…”

Parasite stress promotes homicide and child maltreatment

“…Spatial variation and localization in parasite adaptation against hosts and in host adaptation against parasites, or said differently, in host immune maladaptation against out-group-typical parasites, is a general pattern in the animal and plant infectious disease literature [19,20]. Human cases showing this include (i) the caste-specific infectious diseases and corresponding specific immunity among sympatric castes in India [21], and (ii) the village-specific immune defences against leishmania parasites in adjacent Sudanese villages [22] (also see [9]). …”