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Genetic and functional mapping of gene deserts in complex disease. (360G-Wellcome-094491_Z_10_Z)

It is suggested that as much as 93% of the human genome is transcribed although only 1.5% encodes proteins. The remaining transcriptional activity is presumably due to non-coding RNAs that regulate the expression of distal genes. Transcriptionally active DNA is discernible by the presence of certain histone modifications and transcription factor binding. There are some well-characterised examples of intergenic, transcriptionally active regions which are tissue specific and show limited sequence conservation but are affected by DNA polymorphisms. Some large intergenic regions, ( gene deserts ) have been identified as susceptibility loci in common diseases by genome-wide association studies. This further advocates that non-coding DNA has an important functional role. At least 12 of the 71 loci involved in Crohn's disease (CD) are gene deserts . We will use chromatin immuno-precipitation (ChIP) and RNA profiling to interrogate chromatin architecture and transcriptional activity at thes e loci in intestinal tissues from CD patients. New-generation sequencing (NGS) of recovered DNA and RNA will allow the identification of regulatory regions that co-localise with CD risk SNPs and potentially disease causing. We will then examine regulatory SNPs for association with changes in distal gene expression in primary tissues from CD patients by NGS of mRNA from colonic biopsies.


09 Mar 2011

Grant details
Amount Awarded 471730
Applicant Surname Prescott
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2011-03-09T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title University Award
Internal ID 094491/Z/10/Z
Lead Applicant Dr Natalie Prescott
Planned Dates: End Date 2017-07-31T00:00:00+00:00
Planned Dates: Start Date 2011-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
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