Friddle C, Koskela R, Ranade K, Hebert J, Cargill M, Clark C D, McInnis M, Simpson S, McMahon F, Stine O C, Meyers D, Xu J, MacKinnon D, Swift-Scanlan T, Jamison K, Folstein S, Daly M, Kruglyak L, Marr T, DePaulo J R, Botstein D
Department of Genetics, Stanford University, Stanford, CA, USA.
Am J Hum Genet. 2000 Jan;66(1):205-15. doi: 10.1086/302697.
A genome scan of approximately 12-cM initial resolution was done on 50 of a set of 51 carefully ascertained unilineal multiplex families segregating the bipolar affective disorder phenotype. In addition to standard multipoint linkage analysis methods, a simultaneous-search algorithm was applied in an attempt to surmount the problem of genetic heterogeneity. The results revealed no linkage across the genome. The results exclude monogenic models and make it unlikely that two genes account for the disease in this sample. These results support the conclusion that at least several hundred kindreds will be required in order to establish linkage of susceptibility loci to bipolar disorder in heterogeneous populations.
对51个经过仔细确定的单系多重家庭中的50个进行了初始分辨率约为12厘摩的基因组扫描，这些家庭中双相情感障碍表型呈分离状态。除了标准的多点连锁分析方法外，还应用了一种同步搜索算法，试图克服遗传异质性问题。结果显示全基因组无连锁。这些结果排除了单基因模型，且表明在该样本中由两个基因导致该疾病的可能性不大。这些结果支持这样的结论：在异质人群中，为了确定双相情感障碍易感基因座的连锁关系，至少需要几百个家族。
