title: Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies.
abstract: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated "MEF") to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location.
authors.affiliation: Artchritis 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: Ramsburg
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D002885:Chromosomes, Human, Pair 16; D003241:Consanguinity; D003434:Crossing Over, Genetic; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007557:Israel; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers