Keizo Asami Laboratory (LIKA), Federal University of Pernambuco, Recife, PE, Brazil.
J Mol Neurosci. 2010 May;41(1):193-7. doi: 10.1007/s12031-009-9321-5. Epub 2010 Jan 19.
Genetic variations might contribute to differences in protein activities and gene expression levels observed in complex genetic traits, like neuropsychiatric disease. This finding motivated the development of original approaches using expression studies to guide the finding of new genetic variations. We extended this approach to new genes selected from microarrays studies of brain samples of patients with Alzheimer's disease, major depressive disorder, bipolar affective disorder, and sporadic Creutzfeldt-Jakob disease. The CLCbio Workbench Combined version 3.6.2 was initially used to build expression sites tags (ESTs) and mRNA files retrieved, respectively, from the Goldenpath (UCSC) and NCBI databases and latter to perform multiple batches of Smith-Waterman alignments. The total of 438 ESTs sequences were selected after proper stringent parameters were applied to the first set of mismatches. The annotation revealed various classes of variations, most of them deletions ranging from 1 to 10 pb. These deletions were present in coding regions, 5' and 3' UTR regions. Deletions are often associated to major genetic syndromes with dysmorphic features; however, recent studies show that common microdeletions might be highly associated with common neuropsychiatric disorders.
遗传变异可能导致复杂遗传特征(如神经精神疾病)中观察到的蛋白质活性和基因表达水平的差异。这一发现促使人们开发了使用表达研究来指导寻找新遗传变异的原始方法。我们将这种方法扩展到从阿尔茨海默病、重度抑郁症、双相情感障碍和散发性克雅氏病患者的大脑样本的微阵列研究中选择的新基因。CLCbio Workbench Combined 版本 3.6.2 最初用于分别从 Goldenpath(UCSC)和 NCBI 数据库中构建表达序列标签 (EST) 和 mRNA 文件,然后用于执行多个批次的 Smith-Waterman 比对。在应用适当的严格参数对第一组不匹配项进行筛选后,共选择了 438 个 EST 序列。注释揭示了各种类别的变异,其中大多数缺失长度为 1 到 10 pb。这些缺失存在于编码区、5' 和 3' UTR 区。缺失通常与具有畸形特征的主要遗传综合征有关;然而,最近的研究表明,常见的微缺失可能与常见的神经精神疾病高度相关。
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