BIPOLAR AFFECTIVE-DISORDER PARTIALLY COSEGREGATES WITH A BALANCED T(9-11)(P24-Q23.1) CHROMOSOMAL TRANSLOCATION IN A SMALL PEDIGREE

Analysis of an extended pedigree in which a balanced t(9;11)(p24;q23.1 ) translocation was found to cosegregate with bipolar affective disord er revealed that five of 11 translocation carriers had bipolar affecti ve disorder and one carrier had unipolar depression. There were no aff ected individuals in the pedigree without the balanced translocation, We hypothesized that gene(s) or gene regulatory regions disrupted by t he translocation might be contributing to the bipolar affective disord er in a dominant fashion. To test this hypothesis, we isolated the der ivative chromosome 9 and derivative chromosome 11 in somatic cell hybr ids and identified the nearest flanking markers on chromosome 9 (D9S23 0 and D9S2011E/HRFX3) and chromosome 11 (EST00652 and CRYA2), YAC cont igs were constructed in the region of flanking markers for both chromo somes 9 and 11, Chromosome 11 breakpoint was localized within an 8-kb region in a small insert (100 kb) YAC, Chromosome 9 breakpoint was loc alized within approximately 2 Mb region, Several genes and ESTs includ ing EST00652, CRYA2, DRD2, 5HTR3 on chromosome 11 and VLDLR and SLC1A1 on chromosome 9 were mapped within the vicinity of the breakpoint but were shown not to be disrupted by the translocation breakpoint, Altho ugh several possibilities exist regarding the role of the balanced tra nslocation in developing bipolar affective disorder in this pedigree, including a chance cosegregation, identification of a disrupted gene o r gene regulatory region with the help of physical mapping resources d escribed in this study may help to identify the presence of a suscepti bility gene for this disorder. (C) 1998 Wiley-Liss, Inc.