Hunt for noncoding mutations reveals insights into development of red blood cells

Chasing mutations in the coding regions of genes associated with disease is one thing; chasing noncoding or regulatory mutations is another. For a study published last week in the Proceedings of the National Academy of Sciences, a team led by Vijay Sankaran, Aoi Wakabayashi, and Jacob Ulirsch of Boston Children’s Hospital, Dana-Farber Cancer Institute, and Broad Institute used CRISPR genome editing to probe rare mutations — all in noncoding DNA — linked to three red blood cell diseases. Their findings reveal new insights into the intricate dance of transcription factors involved in red blood cell development, and provide a framework for studying the functional changes wrought by mutations in noncoding stretches of the genome.