ASSIGNMENT OF THE DYSTONIA-PARKINSONISM SYNDROME LOCUS, DYT3, TO A SMALL REGION WITHIN A 1.8-MB YAC CONTIG OF XQ13.1

A YAC contig was constructed of Xq13.1 in order to sublocalize the X-l inked dystonia-parkinsonism (XDP) syndrome locus, DYT3. The contig spa ns a region of similar to 1.8 Mb and includes loci DXS453/DXS348/IL2R gamma/GJB1/CCG1/DXS559. For the construction of the contig, nine seque nce-tagged sites and four short tandem repeat polymorphisms (STRPs) we re isolated. The STRPs, designated as 4704#6 (DXS7113), 4704#7 (DXS711 4), 67601 (DXS7117), and B4Pst (DXS7119) were assigned to a region Ban ked by DXS348 proximally and by DXS559 distally. Their order was DXS34 8/4704 #6/4704 #7/67601/B4Pst/DXS559. They were applied to the analysi s of allelic association and of haplotypes in 47 not-obviously-related XDP patients and in 105 Filipino male controls. The same haplotype wa s found at loci 67601 (DXS7117) and B4Pst (DXS7119) in 42 of 47 patien ts. This percentage of common haplotypes decreased at the adjacent loc i. The findings, together with the previous demonstration of DXS559 be ing the distal nanking marker of DYT3, assign the disease locus to a s mall region in Xq13.1 defined by loci 67601 (DXS7117) and B4Pst (DXS71 19). The location of DYT3 was born out by the application of a newly d eveloped likelihood method for the analysis of linkage disequilibrium.