Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246.
This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbrück formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM).
Levy
E N
EN
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892-1820, USA.
Shen
Y
Y
Kupelian
A
A
Kruglyak
L
L
Aksentijevich
I
I
Pras
E
E
Balow
J E
JE
Linzer
B
B
Chen
X
X
Shelton
D A
DA
Gumucio
D
D
Pras
M
M
Shohat
M
M
Rotter
J I
JI
Fischel-Ghodsian
N
N
Richards
R I
RI
Kastner
D L
DL
D000465:Algorithms; D000483:Alleles; D018912:Arabs / Q000235:genetics; D001136:Armenia; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003198:Computer Simulation; D010505:Familial Mediterranean Fever / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D009018:Morocco