A 6.9-Mb high-resolution BAC/PAC contig of human 4p15.3-p16.1, a candidateregion for bipolar affective disorder

Bipolar affective disorder (BPAD) is a complex disease with a significant g enetic component and a population lifetime risk of 1%. Our previous work id entified a region of human chromosome 4p that showed significant linkage to BPAD in a large pedigree. Here, we report the construction of an accurate, high-resolution physical map of 6.9 Nm of human chromosome 4p15.3-p16.1, w hich includes an 11-cM (5.8 Mb) critical region for BPAD. The map consists of 460 PAC and BAC clones ordered by a combination of STS content analysis and restriction fragment fingerprinting, with a single similar to 300-kb ga p remaining. A total of 289 new and existing markers from a wide range of s ources have been localized on the contig, giving an average marker resoluti on of 1 marker/23 kb. The STSs include 57 ESTs, 9 of which represent known genes, This contig is an essential preliminary to the identification of can didate genes that predispose to bipolar affective disorder, to the completi on of the sequence of the region, and to the development of a high-density SNP map. (C) 2001 Academic Press.