Characterisation of conserved non-coding sequences in vertebrate genomes using bioinformatics, statistics and functional studies
Characterisation of conserved non-coding sequences in vertebrate genomes using bioinformatics, statistics and functional studies
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DOI：
10.1016/j.cbd.2005.03.001
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发表时间：
2006-03-01
影响因子：
3
通讯作者：
Elgar, Greg
中科院分区：
文献类型：
--
作者：
Edwards, Yvonne J. K.;Walter, Klaudia;Elgar, Greg
我们最近发现了大约1400个与脊椎动物[Woolfe，A.，Goodson，M.，Goode，D.K.，Snell，P.，McEwen，G.K.，Vavouri，T.，Smith，S.F.，North，P.，Callaway，H.，Kelly，K.，Walter，K.，Abnizova，I.，Gilks，W.，Edwards，Y.J.K.，J.E.，Elgar，G.，2005]共享的与脊椎动物发育调控有关的保守非编码元件(CNE)。高度保守的非编码序列与脊椎动物的发育有关。PLOS Biol3(1)、E7]。这项研究包含了一个多学科的方法，使用生物信息学、统计学方法和功能分析来识别和表征CNES。使用体内增强子实验，超过90%的被测CNES上调组织特异性GFP表达。在这里，我们回顾了我们的团队在表征脊椎动物中保守的非编码序列领域的研究。我们借此机会讨论我们正在进行的研究，并介绍一些新的和额外的分析结果。包括CNES的系统发生学分析、脊椎动物CNES的序列保守模式以及人类SNPs在CNES中的分布。我们强调了CNE数据集在帮助将健康和疾病中的基因变异关联起来的有效性。我们还讨论了使用增强子实验进行的功能分析以及预测的两个CNES转录因子结合位点的丰富。现在可以公开访问CNES加上注释，并对此进行了说明。这篇综述的内容由Y.J.K.Edwards博士在2004年11月3-6日在日本东京举行的东台河豚功能基因组国际研讨会上介绍。(C)2005 Elsevier Inc.保留所有权利。
We recently identified approximately 1400 conserved non-coding elements (CNEs) shared by the genomes of fugu (Takifugu rubripes) and human that appear to be associated with developmental regulation in vertebrates [Woolfe, A., Goodson, M., Goode, D.K., Snell, P., McEwen, G.K., Vavouri, T., Smith, S.F., North, P., Callaway, H., Kelly, K., Walter, K., Abnizova, I., Gilks, W., Edwards, Y.J.K., Cooke, J.E., Elgar, G., 2005. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3 (1), e7]. This study encompassed a multi-disciplinary approach using bioinformatics, statistical methods and functional assays to identify and characterise the CNEs. Using an in vivo enhancer assay, over 90% of tested CNEs up-regulate tissue-specific GFP expression. Here we review our group's research in the field of characterising non-coding sequences conserved in vertebrates. We take this opportunity to discuss our research in progress and present some results of new and additional analyses. These include a phylogenomics analysis of CNEs, sequence conservation patterns in vertebrate CNEs and the distribution of human SNPs in the CNEs. We highlight the usefulness of the CNE dataset to help correlate genetic variation in health and disease. We also discuss the functional analysis using the enhancer assay and the enrichment of predicted transcription factor binding sites for two CNEs. Public access to the CNEs plus annotation is now possible and is described. The content of this review was presented by Dr. Y.J.K. Edwards at the TODAI International Symposium on Functional Genomics of the Pufferfish, Tokyo, Japan, 3 - 6 November 2004. (c) 2005 Elsevier Inc. All rights reserved.