Riley B, Mogudi-Carter M, Jenkins T, Williamson R
Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, Imperial College, London, UK.
Am J Med Genet. 1996 Nov 22;67(6):515-22. doi: 10.1002/(SICI)1096-8628(19961122)67:6<515::AID-AJMG2>3.0.CO;2-G.
Previous studies have demonstrated possible linkage between chromosome 22 and one of the hypothesized schizophrenia susceptibility genes. Interpretation of these data, however, is not straightforward: although not significant at the level traditionally accepted to demonstrate linkage, reported lod scores were greater than should have occurred by chance for an unlinked marker based on simulation studies. Further, these studies used sample populations which were either of mixed nationality and ethnicity, or mixed ethnic ancestry from one country. We therefore tested for linkage between highly polymorphic chromosome 22 markers and schizophrenia in a sample of southern African Bantu-speaking black families, a population known to have diverged within the last 2,000 years. We also tested one candidate locus, the gene for the soluble form of catechol-O-methyl transferase (COMT) located at 22q11, which has been suggested as the cause of psychiatric symptoms observed in velo-cardio-facial syndrome (VCFS, including DiGeorge syndrome), and which is known to be functionally as well as genetically polymorphic. There is no evidence to support the linkage of markers on chromosome 22 to susceptibility to schizophrenia in this population, using either parametric or nonparametric analysis.
以往的研究已经证明，22号染色体与一种假设的精神分裂症易感基因之间可能存在连锁关系。然而，对这些数据的解释并非直截了当：尽管在传统上认为可证明连锁关系的水平上并不显著，但根据模拟研究，报告的对数优势分数高于非连锁标记偶然出现的情况。此外，这些研究使用的样本群体要么是混合国籍和种族的，要么是来自一个国家的混合种族血统。因此，我们在一个讲班图语的南非黑人家庭样本中测试了高度多态的22号染色体标记与精神分裂症之间的连锁关系，该群体在过去2000年内出现了分化。我们还测试了一个候选基因座，即位于22q11的儿茶酚-O-甲基转移酶（COMT）可溶性形式的基因，该基因被认为是导致心脏颜面综合征（VCFS，包括迪乔治综合征）中观察到的精神症状的原因，并且已知其在功能和基因上都是多态的。无论是使用参数分析还是非参数分析，在这个群体中都没有证据支持22号染色体上的标记与精神分裂症易感性之间存在连锁关系。
