Refined Mapping of the Gene Causing Familial Mediterranean Fever, by Linkage and Homozygosity Studies

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1993 Aug 1

PMID 8328461

Citations 7

Authors

I Aksentijevich

E Pras

L Gruberg

Y Shen

K Holman

S Helling

L Prosen

G R Sutherland

R I Richards

M Ramsburg

Affiliations

Soon will be listed here.

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.

Citing Articles

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Genetic linkage study of familial Mediterranean fever (FMF) to 16p13.3 and evidence for genetic heterogeneity in the Turkish population.

Akarsu A, Saatci U, Ozen S, Bakkaloglu A, Besbas N, Sarfarazi M J Med Genet. 1997; 34(7):573-8.

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Identification of mutations in the duplicated region of the polycystic kidney disease 1 gene (PKD1) by a novel approach.

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Genotypic diagnosis of familial Mediterranean fever (FMF) using new microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.

Dupont M, Dross C, Smaoui N, Nedelec B, Grateau G, Clepet C J Med Genet. 1997; 34(5):375-81.

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Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?.

Aksentijevich I, Gruberg L, Pras E, Balow Jr J, Kovo M, Gazit E Hum Genet. 1993; 91(6):527-34.

PMID: 8340105 DOI: 10.1007/BF00205075.

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