IDENTIFICATION OF POSITIONAL CANDIDATES FOR NEUROLOGICAL DISORDERS ONCHROMOSOME 13Q14-]Q22

In the course of a research project aimed at the molecular characteriz ation of balanced chromosome rearrangements associated with mental ret ardation (MR), several YACs spanning MR-associated chromosomal rearran gements in the 13q14-->q22 region were identified. To facilitate the s earch for relevant candidate genes, we have analyzed a total of 102 ES T clones from this region. Sequence comparisons revealed that these 10 2 clones represent up to 72 distinct transcripts. When no physical map ping data were available, a minimal YAC contig was screened for each u nique transcript by the polymerase chain reaction (PCR) or hybridizati on. Fifty-eight independent ESTs could be localized to YAC clones betw een the markers D13S1248 and D13S1201. Several ESTs are located on YAC clones detecting chromosomal rearrangements in MR patients. One EST w as mapped within the critical region for Rieger syndrome type 2, and t hree transcripts were identified in the region for the nocturnal enure sis type 1. Some ESTs showed homologies to known genes, including the cadherin-related tumor suppressor gene from Drosophila, the yeast mito tic control protein DIS3, and the human alpha-2-macroglobulin receptor associated protein.