A High-Resolution Genetic Map of the Familial Mediterranean Fever Candidate Region Allows Identification of Haplotype-Sharing among Ethnic Groups

• Published in: Genomics (San Diego, Calif.) Calif.), 1997-09, Vol.44 (3), p.280-291
• Main Authors: Balow, James E., Shelton, David A., Orsborn, Annette, Mangelsdorf, Marie, Aksentijevich, Ivona, Blake, Trevor, Sood, Raman, Gardner, Dawn, Liu, Raymond, Pras, Elon, Levy, Ernesto N., Centola, Michael, Deng, Zuoming, Zaks, Nurit, Wood, Geryl, Chen, Xiaoguang, Richards, Neil, Shohat, Mordechai, Livneh, Avi, Pras, Mordechai, Doggett, Norman A., Collins, Francis S., Liu, P.Paul, Rotter, Jerome I., Fischel-Ghodsian, Nathan, Gumucio, Deborah, Richards, Robert I., Kastner, Daniel L.
• Format: Article
• Language: English
• Subjects: Alleles; Armenia - ethnology; Biological and medical sciences; Chromosome Mapping - methods; Chromosomes, Human, Pair 16; Complex syndromes; Egypt - ethnology; Familial Mediterranean Fever - ethnology; Familial Mediterranean Fever - genetics; Haplotypes; Humans; Iraq - ethnology; Jews; Libya - ethnology; Linkage Disequilibrium; Medical genetics; Medical sciences; Recombination, Genetic; Saudi Arabia - ethnology; Tunisia - ethnology
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1997.4860

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designatedMEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placedMEFVin the ∼285 kb betweenD16S468/D16S3070andD16S3376.We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placedMEFVbetweenD16S3082andD16S3373(∼200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only forD16S3370andD16S2617among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.