Gene identification using exon amplification on human chromosome 18q21: implications for bipolar disorder

We previously reported linkage between bipolar disorder and a region on hum an chromosome (HC) 18q21. To identify genes in this region, exon trapping w as performed on cosmids isolated from an HC18-specific cosmid library (LL18 NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridizati on probes. A total of 285 unique sequences (exons) were obtained from 850 s equenced clones. Homology searching of the databases using NCBI's BLAST alg orithms revealed that 31 exons have identity to known genes and/or ESTs, se ven are identical to regions of finished genomic sequences in the 18q21 reg ion, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility reg ion for further study in bipolar disorder or other diseases that map to thi s region.