Fine-structure mapping of the hereditary inclusion body myopathy locus

The gene responsible for a recessive form of hereditary inclusion body myop athy (HIBM) has previously been mapped to a 10-cM interval on chromosome 9p 1-q1. We report the results of further mapping studies using two-point link age analyses and linkage disequilibrium analyses with 20 HIBM: families. We demonstrate that the HIBM gene (HGMW-approved symbol IBM2) lies between lo ci D9S1791 and D9S50, which are about 1 Mb apart. Genetic analyses in 56 af fected individuals of Persian, Afghani, and Iraqi Jewish descent demonstrat ed a common haplotype at these loci, indicating that a founding mutation ac counts for disease in these related ethnic groups. beta-Tropomyosin, an abu ndant skeletal muscle protein that maps within 1 cM of D9S1791, was exclude d as the disease gene because an intragenic polymorphism did not exhibit li nkage disequilibrium in HIBM probands. We conclude that the disease gene re sides in a 1-Mb interval on chromosome 9 and speculate that a novel muscle protein encoded there is mutated in HIBM. (C) 1999 Academic Press.