Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.
Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.
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DOI：
10.1016/j.biopsych.2011.02.015
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发表时间：
2011-10-01
影响因子：
10.6
通讯作者：
Ophoff, Roel A.
中科院分区：
文献类型：
--
作者：
Buizer-Voskamp, Jacobine E.;Muntjewerff, Jan-Willem;Strengman, Eric;Sabatti, Chiara;Stefansson, Hreinn;Vorstman, Jacob A. S.;Ophoff, Roel A.
自2008年以来，已有多项研究报道了精神分裂症的拷贝数变异(CNV)。然而，许多地区是独特的事件，研究之间的重叠最小。这使得很难全面了解精神分裂症病因学中涉及的所有CNV。我们基于一个同质的全基因组数据集，针对所有CNV≥50kb进行了系统的CNV研究。为了补充这一分析，我们回顾了文献中报道的精神分裂症的细胞遗传学和染色体异常，目的是将经典的遗传学发现与我们目前对基因组变异的理解结合起来。我们调查了834名荷兰精神分裂症患者和672名荷兰对照。如果CNV被QuantiSNP和PennCNV检测到，并且包含已知的蛋白质编码基因，则包括CNV。CNV区域和细胞遗传学位点的综合识别指示感兴趣区(CROI)。总共鉴定出2437个CNV，在病例和对照中，每个受试者平均有2.1个CNV。与对照组相比，我们在精神分裂症病例中观察到明显更多的缺失，但没有重复。发现的CNV与以前文献中报道的基因座一致，证实了公认的精神分裂症Crois 1q42和22q11.2，并表明在染色体5q35.1上可能有一个新的CROI。染色体缺失在精神分裂症患者中比在健康受试者中更普遍，因此是致病的危险因素。我们的CNV数据与之前报道的精神分裂症细胞遗传学异常相结合，为位置候选基因提供了一个潜在的有趣区域的概述。
Since 2008 multiple studies have reported on copy number variations (CNVs) in schizophrenia. However, many regions are unique events with minimal overlap between studies. This makes it difficult to gain a comprehensive overview of all CNVs involved in the aetiology of schizophrenia. We performed a systematic CNV study based on a homogeneous genome-wide dataset aiming at all CNVs ≥50 kb. We complemented this analysis with a review of cytogenetic and chromosomal abnormalities for schizophrenia reported in the literature with the purpose to combine classical genetic findings and our current understanding of genomic variation. We investigated 834 Dutch schizophrenia patients and 672 Dutch controls. CNVs were included if they were detected by QuantiSNP as well as PennCNV and contain known protein coding genes. The integrated identification of CNV regions and cytogenetic loci indicates regions of interest (CROIs). In total, 2,437 CNVs were identified with an average number of 2.1 CNVs per subject for both cases and controls. We observed significantly more deletions, but not duplications, in schizophrenia cases versus controls. The CNVs identified coincide with loci previously reported in the literature, confirming well-established schizophrenia CROIs 1q42 and 22q11.2, as well as indicating a potentially novel CROI on chromosome 5q35.1. Chromosomal deletions are more prevalent in schizophrenia patients than in healthy subjects and therefore confer a risk factor for pathogenicity. The combination of our CNV data with previously reported cytogenetic abnormalities in schizophrenia provides an overview of potentially interesting regions for positional candidate genes.
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影响因子：
30.8
作者：
Alkan, Can;Kidd, Jeffrey M.;Marques-Bonet, Tomas;Aksay, Gozde;Antonacci, Francesca;Hormozdiari, Fereydoun;Kitzman, Jacob O.;Baker, Carl;Malig, Maika;Mutlu, Onur;Sahinalp, S. Cenk;Gibbs, Richard A.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
11
作者：
通讯作者：
--
DOI：
10.1016/j.molbrainres.2004.09.029
发表时间：
2004-12-20
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Karayiorgou, M;Gogos, JA
通讯作者：
Gogos, JA
影响因子：
1.7
作者：
Bailey, J. A.;Kidd, J. M.;Eichler, E. E.
通讯作者：
Eichler, E. E.
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C