title: Characterisation of conserved non-coding sequences in vertebrate genomes using bioinformatics, statistics and functional studies.
abstract: 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.
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London, E1 4NS, UK.
authors.forename: Yvonne J K
authors.initials: YJ
authors.lastname: Edwards
authors.forename: Klaudia
authors.initials: K
authors.lastname: Walter
authors.forename: Gayle
authors.initials: G
authors.lastname: McEwen
authors.forename: Tanya
authors.initials: T
authors.lastname: Vavouri
authors.forename: Krystyna A
authors.initials: KA
authors.lastname: Kelly
authors.forename: Irina
authors.initials: I
authors.lastname: Abnizova
authors.forename: Adam
authors.initials: A
authors.lastname: Woolfe
authors.forename: Debbie K
authors.initials: DK
authors.lastname: Goode
authors.forename: Martin
authors.initials: M
authors.lastname: Goodson
authors.forename: Phil
authors.initials: P
authors.lastname: North
authors.forename: Phil
authors.initials: P
authors.lastname: Snell
authors.forename: Heather
authors.initials: H
authors.lastname: Callaway
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Smith
authors.forename: Walter R
authors.initials: WR
authors.lastname: Gilks
authors.forename: Julie E
authors.initials: JE
authors.lastname: Cooke
authors.forename: Greg
authors.initials: G
authors.lastname: Elgar