FAMILIAL MEDITERRANEAN FEVER (FMF) IN MOROCCAN JEWS - DEMONSTRATION OF A FOUNDER EFFECT BY EXTENDED HAPLOTYPE ANALYSIS

Familial Mediterranean fever (FMF) is an autosomal recessive disease c ausing attacks of fever and serositis. The FMF gene (designated ''MEF' ') is on 16p, with the gene order 16cen-D16S80-MEF-D16S94-D16S283-D16S 291-16pter. Here we report the association of FMF susceptibility with alleles at D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significan t associations at D16S283 and D16S291 among the Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Morocca n FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplot ype was present in 6/26 FMF chromosomes versus 1/28 controls. Both gro ups of families are largely descended from Jews who fled the Spanish I nquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic i solation of the Moroccan Jewish community. The lower haplotype frequen cy among non-Moroccan carriers may reflect differences both in history and in population genetics.