Understanding the functional impact of genomic variants is one of the major goals of modern genetics and the underpinning of personalized medicine. To some extent, it is relatively easy to understand how non-synonymous protein coding variants exert their effects. Many synonymous and non-coding variants are known to act by altering the ef?ciency of pre-mRNA splicing. However, in most cases, it is exceedingly dif?cult to predict how these variants impact pre-mRNA splicing. Thus, a method that could simultaneously measure the splicing ef?ciency of thousands of exons and their variants would have a tremendous impact on the ?eld and our understanding of genome function. We propose to develop an assay we call Variant Exon analysis by Sequencing (VEX-Seq) that will facilitate the simultaneous analysis of the impact of intronic and exonic variants on the splicing of thousands of exons. This approach has the potential to have an extremely high impact on our understanding of genome function and how non-coding sequence variants impact pre-mRNA splicing.

Public Health Relevance

Understanding the functional impact of genomic variants is one of the major goals of modern genetics and the underpinning of personalized medicine. The goal of this proposal is to develop a new assay that will facilitate the simultaneous analysis of the impact of intronic and exonic variants on the splicing of thousands of exons. This approach has the potential to have an extremely high impact on our understanding of genome function and how non-coding sequence variants impact pre-mRNA splicing.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HG008799-02
Application #
9187885
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Gilchrist, Daniel A
Project Start
2015-12-01
Project End
2018-11-30
Budget Start
2016-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Genetics
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06032
Adamson, Scott I; Zhan, Lijun; Graveley, Brenton R (2018) Vex-seq: high-throughput identification of the impact of genetic variation on pre-mRNA splicing efficiency. Genome Biol 19:71
Graveley, Brenton R (2016) RNA Matchmaking: Finding Cellular Pairing Partners. Mol Cell 63:186-189