Refined linkage disequilibrium and physical mapping of the gene locus for X-linked dystonia-parkinsonism (DYT3)

X-linked dystonia-parkinsonism (XDP) is a recessive disorder characterized by generalized dystonia with some patients exhibiting parkinsonism. The dis ease gene, DYT3, is located between DXS453 (DXS993) and DXS559, and stronge st linkage disequilibrium is found distal to DXS7117 and proximal to DXS559 . We have isolated and analyzed four novel polymorphic markers between DXS7 117 and DXS559 and, by haplotype analysis, have narrowed the candidate inte rval to <350 kb, A sequence-ready contig of 700 kb has been constructed spa nning DXS7117 to DXS559 and is composed of 35 PACs, BACs, and cosmids. Nine genes and novel ESTs have been mapped into this contig, and mutations in t he coding regions and intron-exon borders of two genes have been excluded a s the cause of XDP. Several of the other genes and ESTs located within the contig code for proteins implicated in normal brain development and functio n and are candidates for DYT3. (C) 1999 Academic Press.