High-Throughput Identification of Genetic Variation Impact on pre-mRNA Splicing Efficiency

AbstractUnderstanding 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 used to test the impact of 2,059 human genetic variants spanning 110 alternative exons on pre-mRNA splicing. This method yields data that reinforces known mechanisms of pre-mRNA splicing, can rapidly identify genomic variants that impact pre-mRNA splicing, and will be useful for increasing our understanding of genome function.