Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan

E.N. Miller, M. Fadl, H.S. Mohamed, A. Elzein, S.E. Jamieson, H.J. Cordell, Christopher Peacock, M. Fakiola, M. Raju, E.A. Khalil, A. Elhassan, A.M. Musa, M.E. Ibrahim, Jenefer Blackwell

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 x 10(-7); empirical p = 1 x 10(-5); lambda(S) 5.1) and 6q27 ( LOD score 3.74; nominal p = 1.68 x 10(-5); empirical p < 1 x 10(-4); lambda(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.
Original languageEnglish
Pages (from-to)0679-0688
JournalPLoS Genetics
Volume3
Issue number5
DOIs
Publication statusPublished - 2007

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