A group of systems biologists in Berlin have developed parallel genome editing in tiny worms to produce diverse indel mutations in regulatory elements in genomic DNA and a powerful software package, crispr-DART, to analyze the indel mutations following targeted DNA sequencing. Using this new approach, they directly map gene regulatory genotypes to physical and physiological attributes in the worm.
The human genome is made up of 40% of regulatory elements that control gene expression. Understanding the function of these regulatory regions is very important for understanding the cause of certain diseases. The study of these regions is complicated because they must be in the context of their genomic and tissue environment and their developmental timeline. To overcome this, researchers at the Max Delbrück Center for Molecular Medicine in Berlin introduced various large-scale mutations using CRISPR-Cas9 in the form of deletions or insertions into the genomes of thousands of C. elegans worms and then monitored the physiological effect of these mutations. In addition, one of the team's bioinformatics researchers developed sequencing software called CRISPR- Downstream Analysis and Reporting Tool (DART), to analyze the generated data. One of their results was the identification of the function of two let-7 microRNA binding sites that work independently in the downstream regulatory region of a gene called lin-41. They were able to show that if one of the two sites were intact, the worms grew normally, otherwise gene expression was incorrect and the worms grew poorly and died.