Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling pathway.
Lithium, an effective drug in the treatment of bipolar disorder, has been proposed to disrupt the Wnt signaling pathway. To facilitate analysis of the possible involvement of elements of the Wnt pathway in human bipolar disorder, a high resolution radiation hybrid mapping (RHM) of these genes was performed. A fine physical location has been obtained for Wnt 7A, frizzled 3, 4 and 5, dishevelled 1, 2 and 3, GSK3beta, axin, alpha-catenin, the Armadillo repeat-containing genes (delta-catenin and ARVCF), and a frizzled-like protein (frpHE) using the Stanford Human Genome Center (SHGC) G3 panel. Most of these genes were previously mapped by fluorescence in situ hybridization (FISH). Frizzled 4, axin and frpHE did not have a previous chromosomal assignment and were linked by RHM to chromosome markers, SHGC-35131 at 11q22.1, NIB1488 at 16p13.3 and D7S2919 at 7p15.2, respectively. Interestingly, some of these genes were found to map within potential regions underlying susceptibility to bipolar disorder and schizophrenia as well as disorders of neurodevelopmental origin. This alternative approach of establishing the precise location of selected genetic components of a candidate pathway and determining if they map within previously defined susceptibility loci should help to identify plausible candidate genes that warrant further analysis through association and mutational scanning.
Rhoads
A R
AR
Department of Biochemistry and Molecular Biology, Howard University, Washington, DC 20059, USA.
Karkera
J D
JD
Detera-Wadleigh
S D
SD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D060466:Axin Protein; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000235:genetics; D017931:DNA Primers; D051180:Desmoplakins; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011828:Radiation Chimera; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins; D051178:alpha Catenin
D048868:Adaptor Proteins, Signal Transducing; D018692:Antimanic Agents; D060466:Axin Protein; C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C000606578:DVL1 protein, human; D051180:Desmoplakins; D000072261:Dishevelled Proteins; C105574:FZD3 protein, human; D051157:Frizzled Receptors; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C092778:WNT7A protein, human; D051153:Wnt Proteins; D051178:alpha Catenin; D008094:Lithium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3