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Title: Identification and characterization of conserved regulatory elements by comparative genomics
Keywords: enhancers, human genome, fugu, forebrain, developmental
Issue Date: 30-Sep-2008
Citation: KRISH JON MATHAVAN (2008-09-30). Identification and characterization of conserved regulatory elements by comparative genomics. ScholarBank@NUS Repository.
Abstract: The aim of this study is to use fugu to identify conserved noncoding elements (CNEs) in genes expressing in the human forebrain, and to characterize selected CNEs in transgenic mice. To this end, genomic sequences for 50 human genes were aligned with their orthologous sequences in mouse and fugu. 206 CNEs associated with 29 genes were identified using the criteria of at least 60% identity over 50 bp. CNEs associated with two transcription factor genes, Six3 and Foxb1, were found to function as cis-regulatory elements by either enhancing or suppressing expression of the reporter gene in a tissue- and developmental-stage specific manner. The regulatory region of orexin (ORX) gene did not contain CNEs but the fugu ORX regulatory region was able to direct neuron-specific expression in the hypothalamus of transgenic mice. Close inspection of sequences revealed cis-regulatory elements with sequence identities below the threshold level of CNEs. Therefore these results show that alternative strategies are required for the identification of all the cis-regulatory elements in the human genome.
Appears in Collections:Ph.D Theses (Open)

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