Fine-structure mapping of the hereditary inclusion body myopathy locus.
The gene responsible for a recessive form of hereditary inclusion body myopathy (HIBM) has previously been mapped to a 10-cM interval on chromosome 9p1-q1. We report the results of further mapping studies using two-point linkage analyses and linkage disequilibrium analyses with 20 HIBM families. We demonstrate that the HIBM gene (HGMW-approved symbol IBM2) lies between loci D9S1791 and D9S50, which are about 1 Mb apart. Genetic analyses in 56 affected individuals of Persian, Afghani, and Iraqi Jewish descent demonstrated a common haplotype at these loci, indicating that a founding mutation accounts for disease in these related ethnic groups. beta-Tropomyosin, an abundant skeletal muscle protein that maps within 1 cM of D9S1791, was excluded as the disease gene because an intragenic polymorphism did not exhibit linkage disequilibrium in HIBM probands. We conclude that the disease gene resides in a 1-Mb interval on chromosome 9 and speculate that a novel muscle protein encoded there is mutated in HIBM.
Eisenberg
I
I
Unit for Development of Molecular Biology and Genetic Engineering, The Hebrew University-Hadassah Medical School, Jerusalem, 91240, Israel.
Thiel
C
C
Levi
T
T
Tiram
E
E
Argov
Z
Z
Sadeh
M
M
Jackson
C L
CL
Thierfelder
L
L
Mitrani-Rosenbaum
S
S
D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D007585:Jews / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic; D014335:Tropomyosin / Q000235:genetics
D014335:Tropomyosin