Localization of the familial Mediterranean fever gene (FMF) to a 250-kb interval in non-Ashkenazi Jewish founder haplotypes

• Published in: American journal of human genetics Vol. 59; no. 3; pp. 603 - 612
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 1996
• Subjects: Biological and medical sciences; Medical sciences; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Genetic mapping; Human; Genetic inheritance; Chromosome E16; Family study; Familial recurrent polyseritis; Genotype; Mutation; Founder effect; Haplotype
• ISSN: 0002-9297; 1537-6605

Chromosome 16p13.3 harbors a gene (MEF) associated with familial Mediterranean fever (FMF), a recessive disease very common in populations of Mediterranean ancestry. In the course of positional cloning of MEF, we genotyped 26 non-Ashkenazi Jewish FMF pedigrees (310 meioses) with 15 microsatellite markers, most of which were recently developed by Genethon. Identification of recombination events in the haplotypes allowed narrowing of the MEF interval to a region between D16S3124 (telomeric) and D16S475 (centromeric). Two markers, D16S3070 and D16S3275, a microsatellite marker isolated from a YAC that also contains D16S3070, showed no recombination with the disease. Linkage disequilibrium and haplotype analysis highlighted the existence of a founder haplotype in our population. The core ancestral alleles were present in 71% of MEF-bearing chromosomes at loci D16S3070 and D16S3275. Furthermore, identification of historical crossing-over events in these pedigrees indicated that MEF is located between these two loci, which are both contained in a 250-kb genomic fragment.