Radiation hybrid mapping of genes in the lithium-sensitive Wnt signaling pathway

Lithium, an effective drug in the treatment of bipolar disorder, has been p roposed to disrupt the Wnt signaling pathway. To facilitate analysis of the possible involvement of elements of the Wnt pathway in human bipolar disor der, a high resolution radiation hybrid mapping (RHM) of these genes was pe rformed. A fine physical location has been obtained for Wnt 7A, frizzled 3, 4 and 5, dishevelled 1, 2 and 3, GSK3 beta, axin, alpha-catenin, the Armad illo repeat-containing genes (delta-catenin and ARVCF), and a frizzled-like protein (frpHE) using the Stanford Human Genome Center (SHGC) G3 panel. Mo st of these genes were previously mapped by fluorescence in situ hybridizat ion (FISH). Frizzled 4, axin and frpHE did not have a previous chromosomal assignment and were linked by RHM to chromosome markers, SHGC-35131 at 11q2 2.1, 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 o f 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 shoul d help to identify plausible candidate genes that warrant further analysis through association and mutational scanning.