DLG3,the Gene Encoding Human Neuroendocrine Dlg (NE-Dlg), Is Located within the 1.8-Mb Dystonia–Parkinsonism Region at Xq13.1

Abstract

Neuroendocrine-Dlg (NE-Dlg) is a member of the discs-large-related (DLG) subfamily of the membrane-associated guanylate kinase-related protein family. Based on evidence from model systems, this protein appears to be critical for synaptogenesis, acting as a site-specific organizational center for integral membrane proteins and their downstream signaling molecules associated with the cytoskeleton. NE-Dlg also directly interacts with the colorectal tumor suppressor adenomatous polyposis coli, suggesting that it may play a role in regulating cell proliferation in epithelial cells. To explore the genetic control of NE-Dlg, we developed a physical map of the chromosome region containingDLG3,the locus encoding NE-Dlg. Using human–hamster radiation hybrid mapping panels, we mappedDLG3to Xq13.1 and established a sequence-tagged site marker map of the surrounding region. We then developed a yeast artificial chromosome (YAC) contig for this region. Encompassing approximately 2.0 Mb contained within five overlapping YACs, this contig also includes the dystonia–parkinsonism syndrome (DYT3) locus. The close proximity ofDLG3to theDYT3region suggests that the gene encoding NE-Dlg is a candidate locus for this neurological disorder.