Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Effects of Human Genetic Variation on the Structure of mRNA UTRs
The 5? and 3? untranslated regions (UTRs) of genes play a central regulatory role in the cell. Although generally not considered to contain highly structured RNA, the accessibility of specific regions in the mRNA UTRs is a critical component of the cell?s regulatory machinery. To assess the potential of Single Nucleotide Polymorphisms (SNPs) to affect the structure of UTRs we used an RNA partition function calculation approach to scan all known SNPs within human UTRs. We identified in particular 5 SNPs in the PTEN promoter that cause a significant change in UTR structure, which we confirmed using chemical mapping with the CAFA (Capillary Automated Footprinting Analysis) approach. These SNPs are associated with Cowden Syndrome (multiple hamartoma) and lead to increased risk of cancer. We also identified the subset human SNPs that cause the largest changes in RNA structure, including a SNP in the 3? UTR of the OAS1 gene that is associated with weakened innate immunity. This approach allows us to identify SNPs that have the potential to significantly affect RNA structure. In turn we are able to evaluate the potential molecular causes of particular genetic associations.
1Computational and Structural Biology