Balow J E, Shelton D A, Orsborn A, Mangelsdorf M, Aksentijevich I, Blake T, Sood R, Gardner D, Liu R, Pras E, Levy E N, Centola M, Deng Z, Zaks N, Wood G, Chen X, Richards N, Shohat M, Livneh A, Pras M, Doggett N A, Collins F S, Liu P P, Rotter J I, Kastner D L
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892-1820, USA.
Genomics. 1997 Sep 15;44(3):280-91. doi: 10.1006/geno.1997.4860.
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 approximately 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 (approximately 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.
家族性地中海热（FMF）是一种由位于16号染色体p13.3上的一个基因（命名为MEFV）发生突变引起的隐性炎症性疾病。我们最近构建了一个包含FMF关键区域的1兆碱基的黏粒重叠群。在此，我们展示了FMF家族中来自我们物理图谱的12个标记的基因型数据，包括5个新鉴定的微卫星。家系内重组将MEFV定位在D16S468/D16S3070和D16S3376之间约285千碱基的区域。我们在北非犹太人群体中观察到显著的连锁不平衡，并且在奠基者单倍型中的历史重组将MEFV定位在D16S3082和D16S3373之间（约200千碱基）。在伊拉克犹太、阿拉伯和亚美尼亚家族的较小样本中，亚美尼亚人群体中仅D16S3370和D16S2617存在显著的等位基因关联。相当一部分伊拉克犹太和亚美尼亚携带者染色体似乎源自北非犹太祖先单倍型。我们观察到一种伊拉克犹太人、阿拉伯人和亚美尼亚人共有的独特FMF单倍型以及另外两种分别局限于伊拉克犹太人群体或亚美尼亚人群体的单倍型。这些数据支持这样一种观点，即少数几个主要突变占FMF病例的很大比例，并表明其中一些突变在受影响的中东人群彼此分化之前就已出现。
