Increase in GSK3β gene copy number variation in bipolar disorder
Increase in GSK3β gene copy number variation in bipolar disorder
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DOI：
10.1002/ajmg.b.30498
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发表时间：
2007-04-05
影响因子：
2.8
通讯作者：
Stopkova, Pavla
中科院分区：
文献类型：
--
作者：
Lachman, Herbert M.;Pedrosa, Erika;Stopkova, Pavla
亚显微拷贝数变异（CNVs），也称为拷贝数多态性（CNP）的分析，正在成为了解癌症，发育障碍和复杂性状的遗传基础的新工具。这可能特别有用的一个领域是鉴定精神分裂症（SZ）和双相情感障碍（BD）的遗传变异。在过去的十年中进行的连锁分析和药理学研究涉及到一些位置和生理候选基因。然而，尽管进行了广泛的分析，导致疾病易感性的潜在等位基因变异在很大程度上仍然是难以捉摸的。虽然大多数CNV的边界尚未被精确定位，但似乎相当数量的SZ和BD候选基因的编码元件被多态性CNV破坏，这表明这些将是考虑潜在疾病易感性的良好变体。一个这样的基因是GSK 3 β，其编码糖原合成酶激酶，其是Wnt信号传导途径的关键组分和锂盐的靶标。位于染色体3q13.3处的GSK 3 β基因座中的CNV似乎破坏了该基因的3 '编码元件。CNV还影响其他两个注释基因。我们现在报告，BD患者与对照组相比，CNV（主要是重复变异）的频率增加（P = 0.002）。这一发现表明，GSK 3 β可能与某些个体的BD易感性有关，并且应该将该基因和其他精神疾病候选基因中的CNV作为致病性功能性遗传变异进行分析。(c)2007 Wiley-Liss，Inc.
The analysis of submicroscopic copy number variations (CNVs), also known as copy number polymorphisms (CNPs), is emerging as a new tool for understanding the genetic basis of cancer, developmental disorders, and complex traits. One area where this may be particularly useful is in the identification of genetic variants underlying schizophrenia (SZ) and bipolar disorder (BD). Linkage analysis and pharmacological studies carried out over the past decade have implicated a number of positional and physiological candidate genes. Yet, despite extensive analysis, the underlying allelic variants responsible for disease susceptibility have remained, largely, elusive. Although the borders of most CNV have not been precisely mapped, it appears that a considerable number of SZ and BD candidate genes have their coding elements disrupted by polymorphic CNVs, suggesting that these would be good variants to consider for underlying disease susceptibility. One such gene is GSK3 beta, which codes for glycogen synthase kinase, a key component of the Wnt signaling pathway and a target of lithium salts. A CNV in the GSK3 beta locus at chromosome 3q13.3 appears to disrupt the gene's 3'-coding elements. The CNV also affects two other annotated genes. We now report that patients with BD have an increased frequency of this CNV-primarily the duplication variant-compared with controls (P = 0.002). The finding suggests that GSK3 beta may be involved in BD susceptibility in some individuals and that CNVs in this and other candidate genes for psychiatric disorders should be analyzed as causative functional genetic variants. (c) 2007 Wiley-Liss, Inc.