title: Familial Mediterranean fever (FMF) in Moroccan Jews: demonstration of a founder effect by extended haplotype analysis.
abstract: Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated "MEF") is on 16p, with the gene order 16cen-D16S80-MEF-D16S94-D16S283-D16S291-++ +16pter. Here we report the association of FMF susceptibility with alleles as D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significant 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 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lower haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: I
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: E
authors.initials: E
authors.lastname: Pras
authors.forename: L
authors.initials: L
authors.lastname: Gruberg
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: K
authors.initials: K
authors.lastname: Holman
authors.forename: S
authors.initials: S
authors.lastname: Helling
authors.forename: L
authors.initials: L
authors.lastname: Prosen
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: R I
authors.initials: RI
authors.lastname: Richards
authors.forename: M
authors.initials: M
authors.lastname: Dean
mesh_terms: D000483:Alleles; D016009:Chi-Square Distribution; D002885:Chromosomes, Human, Pair 16; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D009018:Morocco / Q000208:ethnology; D012150:Polymorphism, Restriction Fragment Length; D013030:Spain / Q000208:ethnology
chemical_list: D005819:Genetic Markers