Characterisation of conserved non-coding sequences in vertebrate genomes using bioinformatics, statistics and functional studies

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• 作者：Yvonne J.K. Edwards ; Klaudia Walter ; Gayle McEwen ; Tanya Vavouri ; Krystyna A. Kelly ; Irina Abnizova ; Adam Woolfe ; Debbie K. Goode ; Martin Goodson ; Phil North ; Phil Snell ; Heather Callaway ; Sarah F. Smith ; Walter R. Gilks ; Julie E. Cooke ; Greg Elgar
• 关键词：Conserved non-coding elements ; Comparative genomics ; Functional genomics ; Vertebrates ; Takifugu rubripes ; Bioinformatics ; In vivo enhancer assay
• 刊名：Comparative Biochemistry and Physiology Part D: Genomics and Proteomics
• 出版年：2006
• 出版时间：March 2006
• 年：2006
• 卷：1
• 期：1
• 页码：46-58
• 全文大小：360 K

文摘

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.