YAC and Cosmid Contigs Encompassing the Fukuyama-Type Congenital Muscular Dystrophy (FCMD) Candidate Region on 9q31

Abstract

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31–q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this candidate region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3.5 Mb, which includes this D9S306–D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site,Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen–D9S127–(∼800 kb)–D9S306 (identical to D9S53)–(∼700 kb)–A107XF9–(∼500 kb)–D9S172–(∼30 kb)–D9S299 (identical to D9S774)–(∼120 kb)–WI2269–tel. Thus, we have constructed the first high-resolution physical map of the FCMD candidate region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this region.