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Tuesday, January 22

How Single-Nucleotide Polymorphisms Affect the Decomposition of Introns

Dr. Richard J. Feldmann, Global Determinants, Inc., Derwood, Maryland
BSEC Seminar
2:00 PM — 3:00 PM, Weinberg Auditorium, Building 4500N
Contact: Kristina (Munoz-Flores) Thiagarajan (thiagarajakd@ornl.gov ), 865.241.5214

Abstract

A number of seemingly isolated facts form an interesting pattern that may help to resolve many diseases:
• Highly Repeated Sequences (HRSs)that are the detritus of transposable elements and viruses constitute 50% or more of higher eukaryotic genomes.
• HRSs can be inserted into the genome in either direction.
• Gene-Coding elements constitute less than 5% of the genome while Non-Coding elements constitute an additional 35%.
• Gene-Coding and Non-Coding elements act as the source of RNAs for many different uses (e.g., iRNAs, Connectrons, piwis).
• The stability of a cell may depend on the production of these RNAs.
• The three million single-nucleotide polymorphisms (SNPs) in an individual's genome are thought to be uniformly distributed across the chromosomes.
• Whereas exons are relatively short, introns follow a classic Pareto length distribution, so the probability of SNPs occurring in introns is much greater.

When transcribed, released by editing, and folded, introns with opposing HRSs form long stems that can be clipped by the Dicer enzyme. Each Dicer action turns one molecule into three shorter molecules. These three molecules can refold, and if they contain Dicer-length or longer stems, they too will be clipped. Twenty-eight percent of all introns in humans contain one or more Dicer stems. Dicer has the effect of transforming an intron into a collection of small to medium-sized RNA fragments (i.e., 20 to 1,000 bases).

The computational, experimental question (that Dr. Feldmann has been addressing) is whether SNPs in the Dicer stems change the collection of RNA fragments produced by Dicer's recursive action.

About the speaker In 1967, Dr. Feldmann went to the National Institutes of Health to effect the connection between computers and medical problems. He retired in 1966, and since then, he has been thinking about genomes. In 1999, he discovered four-sequence relationships called "Connectrons" that are thought to control the expression of Gene-Coding and Non-Coding elements in all genomes.