Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease.
Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease.
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DOI：
10.1176/appi.ajp.2009.09071016
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Brzustowicz LM
中科院分区：
文献类型：
--
作者：
Bassett AS;Scherer SW;Brzustowicz LM
DNA的结构变异，如拷贝数变异（CNV），被认为有助于正常的基因组变异和人类疾病的风险。例如，精神分裂症与22q11.2缺失有明确的联系。最近的全基因组研究提供了初步证据，表明其他基因座的CNV也可能与精神分裂症有关。在这篇文章中，作者提供了CNVs的简要概述，回顾了最近与精神分裂症相关的发现，概述了临床实践和诊断亚型的影响，并对未来的CNVs报告提出了建议，以改善结果的解释。该综述包括精神分裂症CNVs的全基因组调查，其中包括一个或多个比较组，在2009年之前发表，并使用更新的方法。确定了6项研究。尽管存在一些局限性，这些最初的全基因组CNV研究提供了精神分裂症与罕见的1q21.1和15q13.3缺失的重复关联。总的来说，这些结果指出了一个更普遍的突变机制，涉及罕见的CNV，这些CNV会增加精神分裂症的风险，特别是这种疾病的更多发育形式。包括22q11.2缺失在内，罕见的风险相关CNV似乎占精神分裂症的2%。更明显的CNVs对临床实践和诊断亚型有直接的意义。具有较低拷贝数的CNVs有望有助于我们对发病机制的遗传理解。这些发现为精神分裂症提供了比以前设想的更广泛的神经精神谱系，并为遗传研究指明了新的方向。
Structural variations of DNA, such as copy number variations (CNVs), are recognized to contribute both to normal genomic variability and to risk for human diseases. For example, schizophrenia has an established connection with 22q11.2 deletions. Recent genome-wide studies have provided initial evidence that CNVs at other loci may also be associated with schizophrenia. In this article, the authors provide a brief overview of CNVs, review recent findings related to schizophrenia, outline implications for clinical practice and diagnostic subtyping, and make recommendations for future reports on CNVs to improve interpretation of results. The review included genome-wide surveys of CNVs in schizophrenia that included one or more comparison groups, were published before 2009, and used newer methods. Six studies were identified. Despite some limitations, these initial genome-wide studies of CNVs provide replicated associations of schizophrenia with rare 1q21.1 and 15q13.3 deletions. Collectively, the results point to a more general mutational mechanism involving rare CNVs that elevate risk for schizophrenia, especially more developmental forms of the disease. Including 22q11.2 deletions, rare risk-associated CNVs appear to account for up to 2% of schizophrenia. The more penetrant CNVs have direct implications for clinical practice and diagnostic subtyping. CNVs with lower penetrance promise to contribute to our genetic understanding of pathogenesis. The findings provide insight into a broader neuropsychiatric spectrum for schizophrenia than previously conceived and indicate new directions for genetic studies.
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影响因子：
30.8
作者：
Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
64.8
作者：
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通讯作者：
Scherer, Stephen W.
影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
DOI：
10.1111/j.1365-2788.2004.00621.x
发表时间：
2004-09-01
影响因子：
3.6
作者：
Greenwood, CMT;Husted, J;Bassett, AS
通讯作者：
Bassett, AS