TY - JOUR
T1 - A high-resolution genetic map of the Familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups
AU - Balow, James E.
AU - Shelton, David A.
AU - Orsborn, Annette
AU - Mangelsdorf, Marie
AU - Aksentijevich, Ivona
AU - Blake, Trevor
AU - Sood, Raman
AU - Gardner, Dawn
AU - Liu, Raymond
AU - Pras, Elon
AU - Levy, Ernesto N.
AU - Centola, Michael
AU - Deng, Zuoming
AU - Zaks, Nurit
AU - Wood, Geryl
AU - Chen, Xiaoguang
AU - Richards, Neil
AU - Shohat, Mordechai
AU - Livneh, Avi
AU - Pras, Mordechai
AU - Doggett, Norman A.
AU - Collins, Francis S.
AU - Liu, P. Paul
AU - Rotter, Jerome I.
AU - Fischel-Ghodsian, Nathan
AU - Gumucio, Deborah
AU - Richards, Robert I.
AU - Kastner, Daniel L.
N1 - Funding Information:
This work was performed in partial ful®llment of the requirements for a Master of Sciences degree at George Washington University. We thank Dr. Alejandro SchaÈffer for help in setting up FASTLINK on our computer. N.F.-G. and X.C. gratefully acknowledge the support of the Arthritis Foundation. N.A.D. was supported by the U.S. DOE under Contract W-7405-ENG-36. D.L.G. is grateful to the Michigan Multipurpose Arthritis Center, NIH P60 AR20557, for pilot study support.
PY - 1997/9/15
Y1 - 1997/9/15
N2 - Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) 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 placed MEFV in the ~285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (~200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among 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.
AB - Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) 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 placed MEFV in the ~285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (~200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among 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.
UR - http://www.scopus.com/inward/record.url?scp=0031572315&partnerID=8YFLogxK
U2 - 10.1006/geno.1997.4860
DO - 10.1006/geno.1997.4860
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C2 - 9325049
AN - SCOPUS:0031572315
VL - 44
SP - 280
EP - 291
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 3
ER -