Human homolog of the mouse imprinted gene Impact resides at the pericentric region of chromosome 18 within the critical region for bipolar affective disorder

Several mapping studies of families with multiple individuals who have bipo lar affective disorder (BPAD) have demonstrated possible linkage of the tra it to the pericentric region of chromosome 18 (18cen). Currently, the large size of the critical interval defined by these studies makes effective sel ection of candidate genes formidable. However, documentation of 18cen-linke d families in which a parent-of-origin effect was observed in the transmiss ion of the BPAD trait provides a clue to the nature of the putative gene; i t may be imprinted. In the present study, we cloned IMPACT, the human homol og of the mouse imprinted gene Impact and mapped it to 18cen within the cri tical interval for BPAD. Human IMPACT encodes a protein with 320 amino acid s and is expressed at high levels in the brain. Since only a small number o f imprinted genes are estimated to be present in the entire genome, very fe w imprinted genes would be expected to be present in this particular chromo somal region. Hence, IMPACT represents a candidate gene for BPAD susceptibi lity. Alternatively, other as yet unknown imprinted gene(s) adjacent to IMP ACT could contribute to the BPAD trait, since multiple imprinted genes may occasionally form clusters. Localization of human IMPACT at 18cen in this s tudy defines a promising target region in which to search for putative BPAD genes.