DLG3, THE GENE ENCODING HUMAN NEUROENDOCRINE DLG (NE-DLG), IS LOCATEDWITHIN THE 1.8-MB DYSTONIA-PARKINSONISM REGION AT XQ13.1

Neuroendocrine-Dlg (NE-Dlg) is a member of the discs-large-related (DL G) subfamily of the membrane-associated guanylate kinase-related prote in family. Based on evidence from model systems, this protein appears to be critical for synaptogenesis, acting as a site-specific organizat ional center for integral membrane proteins and their downstream signa ling molecules associated with the cytoskeleton, NE-Dlg also directly interacts with the colorectal tumor suppressor adenomatous polyposis c oli, suggesting that it may play a role in regulating cell proliferati on in epithelial cells. To explore the genetic control of NE-Dlg, we d eveloped a physical map of the chromosome region containing DLG3, the locus encoding NE-Dlg. Using human-hamster radiation hybrid mapping pa nels, we mapped DLG3 to Xq13.1 and established a sequence-tagged site marker map of the surrounding region. We then developed a yeast artifi cial chromosome (YAC) contig for this region, Encompassing approximate ly 2.0 Mb contained within five overlapping YACs, this contig also inc ludes the dystonia-parkinsonism syndrome (DYT3) locus. The close proxi mity of DLG3 to the DYT3 region suggests that the gene encoding NE-Dlg is a candidate locus for this neurological disorder. (C) 1998 Academi c Press.