Abstract
Understanding the functional impact of genomic variants is a major goal of modern genetics and personalized medicine. Although many synonymous and non-coding variants act through altering the efficiency of pre-mRNA splicing, it is difficult to predict how these variants impact pre-mRNA splicing. Here, we describe a massively parallel approach we use to test the impact on pre-mRNA splicing of 2059 human genetic variants spanning 110 alternative exons. This method, called variant exon sequencing (Vex-seq), yields data that reinforce known mechanisms of pre-mRNA splicing, identifies variants that impact pre-mRNA splicing, and will be useful for increasing our understanding of genome function.
Highlights
One of the main goals of personalized medicine is to understand how genetic variations between individuals impact health
Genetic variants can impact health in a number of different ways, one of which is through altering pre-mRNA splicing efficiency
We set out to develop a high-throughput reporter system to determine the impact of genomic variants on pre-mRNA splicing
Summary
One of the main goals of personalized medicine is to understand how genetic variations between individuals impact health. Exonic splicing enhancers and silencers (ESEs and ESSs), as well as intronic splicing enhancers and silencers (ISEs and ISSs), are examples of splicing regulatory elements that can be perturbed and result in different splicing outcomes. Modulation of these splicing regulatory elements has been shown to be disease associated (for a review see [4]). Understanding how both intronic and exonic variants impact splicing provides insights into the mechanisms of splicing, and is important to understand the basis of certain genetic diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
