Sarah J. Wheelan, MD, PhD, (Institute of Genetic Medicine)

Michael C. Schatz, PhD, (Department of Computer Science)

The non-contiguous nature of eukaryotic coding sequences generates immense protein and RNA diversity from one gene, and poses a challenge for scientists investigating gene function. Short-read sequencing captures tiny snapshots of the immense combinatorial problem; thus, we have likely identified only a small fraction of the functional transcripts in any cell. A novel mechanism is possible: chromatin structure places genes in physical proximity and creates opportunities for RNA-level rearrangements, without corresponding DNA rearrangements. These have been reported anecdotally and would be a mechanism for creating immense transcript diversity. Such transcripts may be detectable only in large and validated datasets, by fast and sensitive algorithms. Longer-read technology, well known to our group, may also be employed.