CRISPR/Cas9-Mediated Scanning for Regulatory Elements Required for HPRT1 Expression via Thousands of Large, Programmed Genomic Deletions

The extent to which non-coding mutations contribute to Mendelian disease is a major unknown in human genetics. Relatedly, the vast majority of candidate regulatory elements have yet to be functionally validated. Here, we describe a CRISPR-based system that uses pairs of guide RNAs (gRNAs) to program thousands of kilobase-scale deletions that deeply scan across a targeted region in a tiling fashion ( “ScanDel”). We applied ScanDel to HPRT1, the housekeeping gene underlying Lesch-Nyhan syndrome, an X-linked recessive disorder.

Source: The American Journal of Human Genetics - July 13, 2017 Category: Genetics & Stem Cells Authors: Molly Gasperini, Gregory M. Findlay, Aaron McKenna, Jennifer H. Milbank, Choli Lee, Melissa D. Zhang, Darren A. Cusanovich, Jay Shendure Tags: Article Source Type: research