Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD 21205, USA.
Biol Psychiatry. 2012 Oct 15;72(8):651-4. doi: 10.1016/j.biopsych.2012.06.014. Epub 2012 Jul 15.
Clinical studies have identified several regions of the genome with copy number variations (CNVs) associated with diverse neurodevelopmental behavioral disorders.
We analyzed 1 million (M) single nucleotide polymorphism genotype arrays for evidence of previously reported recurrent CNVs and enriched genome-wide CNV burden in DNA from 600 brains, including 441 individuals with various psychiatric diagnoses. We explored gene expression in the dorsolateral prefrontal cortex in selected cases with CNVs and in other subjects with Illumina BeadArrays (568 subjects in total) and additionally in 66-92 subjects with quantitative real-time polymerase chain reaction.
The CNVs in previously reported genomic regions were identified in 4 of 193 patients with the diagnosis of schizophrenia (1q21.1, 11q25, 15q11.2, 22q11), 4 of 238 patients with mood disorders (11q25, 15q11.2, 22q11), and 1 of 10 patients with autism (2p16.3). No evidence of increased genome-wide CNV burden was observed in cases with schizophrenia or mood disorders, although the study is underpowered to observe rare events. Messenger RNA expression patterns suggested incomplete molecular penetrance of observed CNVs.
Our data confirm in brain DNA the presence of certain recurrent CNVs in a small percentage of patients with psychiatric diagnoses.
临床研究已经确定了基因组中与多种神经发育行为障碍相关的多个区域存在拷贝数变异(CNVs)。
我们分析了 100 万个单核苷酸多态性基因分型阵列,以寻找先前报道的反复出现的 CNV 证据,并在来自 600 个大脑的 DNA 中富集全基因组 CNV 负担,包括 441 名具有各种精神诊断的个体。我们在具有 CNV 的选定病例和其他具有 Illumina BeadArray 的个体(总共 568 名个体)中以及在具有定量实时聚合酶链反应的 66-92 名个体中探索了背外侧前额叶皮层中的基因表达。
在 193 名精神分裂症患者(1q21.1、11q25、15q11.2、22q11)、238 名情绪障碍患者(11q25、15q11.2、22q11)和 10 名自闭症患者(2p16.3)中发现了先前报道的基因组区域中的 CNVs。尽管该研究没有足够的能力来观察罕见事件,但在精神分裂症或情绪障碍患者中未观察到全基因组 CNV 负担增加的证据。信使 RNA 表达模式表明观察到的 CNVs 的不完全分子外显率。
我们的数据在脑 DNA 中证实了某些具有精神诊断的患者中存在一定比例的反复出现的 CNVs。