AN INTEGRATED PHYSICAL MAP OF 18P11.2 - A SUSCEPTIBILITY REGION FOR BIPOLAR DISORDER

The reported linkage between bipolar disorder and a large pericentric portion of chromosome 18 has been replicated in an independent study. Further examination of this region showed that 18p11.2 had the greates t allele sharing in our pedigrees and increased sharing in other indep endently ascertained pedigree series permitting refinement of the regi on of significance. To facilitate positional cloning of a susceptibili ty gene, we used a combination of mapping reagents, including a subchr omosomal somatic cell hybrid panel, a contig of clones in yeast artifi cial chromosomes (YAC), and a radiation hybrid (RH) panel, to construc t a high resolution physical map of the region including sequence tag sites (STSs) and expressed sequence tags (ESTs). This approach generat ed the interlocus distance and order of 15 STSs and 16 ESTs including four novel transcripts, with an average of similar to 200 kb between l oci, over a similar to 6-Mb region. This high resolution integrated ma p will be an important tool in providing loci for contig construction, and positional candidates for mutation screening.