Baysal B E, Potkin S G, Farr J E, Higgins M J, Korcz J, Gollin S M, James M R, Evans G A, Richard C W
Department of Psychiatry, Western Psychiatric Institute and Clinic, The University of Pittsburgh Medical Center, Pennsylvania 15213-2593, USA.
Am J Med Genet. 1998 Feb 7;81(1):81-91.
Analysis of an extended pedigree in which a balanced t(9;11)(p24;q23.1) translocation was found to cosegregate with bipolar affective disorder revealed that five of 11 translocation carriers had bipolar affective disorder and one carrier had unipolar depression. There were no affected individuals in the pedigree without the balanced translocation. We hypothesized that gene(s) or gene regulatory regions disrupted by the translocation might be contributing to the bipolar affective disorder in a dominant fashion. To test this hypothesis, we isolated the derivative chromosome 9 and derivative chromosome 11 in somatic cell hybrids and identified the nearest flanking markers on chromosome 9 (D9S230 and D9S2011E/HRFX3) and chromosome 11 (EST00652 and CRYA2). YAC contigs were constructed in the region of flanking markers for both chromosomes 9 and 11. Chromosome 11 breakpoint was localized within an 8-kb region in a small insert (100 kb) YAC. Chromosome 9 breakpoint was localized within approximately 2 Mb region. Several genes and ESTs including 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. Although several possibilities exist regarding the role of the balanced translocation in developing bipolar affective disorder in this pedigree, including a chance cosegregation, identification of a disrupted gene or gene regulatory region with the help of physical mapping resources described in this study may help to identify the presence of a susceptibility gene for this disorder.
对一个扩展家系进行分析，发现其中一个平衡的t(9;11)(p24;q23.1)易位与双相情感障碍共分离，结果显示11名易位携带者中有5人患有双相情感障碍，1名携带者患有单相抑郁症。该家系中没有携带平衡易位的未患病个体。我们推测，易位所破坏的基因或基因调控区域可能以显性方式导致双相情感障碍。为了验证这一假设，我们在体细胞杂种中分离出衍生9号染色体和衍生11号染色体，并确定了9号染色体（D9S230和D9S2011E/HRFX3）和11号染色体（EST00652和CRYA2）上最邻近的侧翼标记。在9号和11号染色体侧翼标记区域构建了酵母人工染色体（YAC）重叠群。11号染色体断点定位于一个小插入（100 kb）YAC中的一个8 kb区域内。9号染色体断点定位于大约2 Mb区域内。包括11号染色体上的EST00652、CRYA2、DRD2、5HTR3以及9号染色体上的VLDLR和SLC1A1在内的几个基因和EST被定位在断点附近，但未显示被易位断点破坏。尽管关于这个家系中平衡易位在双相情感障碍发生中的作用存在多种可能性，包括偶然共分离，但借助本研究中描述的物理图谱资源鉴定出一个被破坏的基因或基因调控区域，可能有助于确定该疾病易感基因的存在。
