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. 1996 Mar;58(3):523–534.

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246.

E N Levy 1, Y Shen 1, A Kupelian 1, L Kruglyak 1, I Aksentijevich 1, E Pras 1, J E Balow Jr 1, B Linzer 1, X Chen 1, D A Shelton 1, D Gumucio 1, M Pras 1, M Shohat 1, J I Rotter 1, N Fischel-Ghodsian 1, R I Richards 1, D L Kastner 1
PMCID: PMC1914560  PMID: 8644712

Abstract

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbrück formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM).

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Selected References

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