LINKAGE-DISEQUILIBRIUM MAPPING NARROWS THE FUKUYAMA-TYPE CONGENITAL MUSCULAR-DYSTROPHY (FCMD) CANDIDATE REGION TO LESS-THAN-100 KB

Fukuyama-type congenital muscular dystrophy (FCMD), the second most co mmon form of muscular dystrophy in Japan, is an autosomal recessive se vere muscular dystrophy associated with brain anomalies. After our ini tial mapping of the FCMD locus to chromosome 9q31-33, we have further defined the locus within a similar to 5-cM region between D9S127 and D 9S2111 and have found linkage disequilibrium between FCMD and D9S306 i n this candidate region on 9q31. The high prevalence of FCMD among the Japanese, who are a relatively isolated population, provides an oppor tunity to utilize linkage-disequilibrium mapping. We developed three n ew microsatellites, near D9S306, from the FCMD YAC contig, determined their positions on YACs, and performed linkage-disequilibrium mapping with these markers and other newly published loci. The maximum value o f p(excess), which represents the strength of linkage disequilibrium, was obtained at D9S2107; and this value showed a relatively steady ris e and fall across the region that is likely to contain FCMD. Distances between FCMD and each marker were presumed to be similar to 1 Mb, sim ilar to 350 kb, similar to 140 kb, similar to 20 kb, similar to 280 kb , similar to 450 kb, and similar to 740 kb for D9S306, A107XF9, D9S210 5, D9S2107, D9S172, D9S299, and D9S2109, respectively. Haplotype analy sis using the three closest markers D9S2105, D9S2107, and D9S172 indic ated that most FCMD-bearing chromosomes are derived from a single ance stral founder and suggested that these markers can be used for the dia gnosis of sporadic FCMD. Thus, the FCMD gene is most likely to lie wit hin a region of <100 kb containing D9S2107.