Duchenne muscular dystrophy (DMD) is a lethal pediatric disease caused by mutations in the enormous DMD gene. The DMD gene contains 79 exons and spans 2 megabases – one of the largest in the human genome. Multiple messenger RNA isoforms which are “working copies” of the gene, have been described but recent data suggests an enormity of potential isoforms, some of which will have therapeutic value. With 79 exons, a theoretical 2⁷⁹-1 potential isoforms exist although much fewer are expected to exist. We and others have observed that some individuals with DMD mutations express unusual DMD isoforms that may explain the relative mildness of their disease relative to the general DMD population.

In recent years, a large number of RNA-seq experiments have been performed on tissues and cells of human origin. Most of these experiments, however, are not focused on DMD transcripts. We aim to leverage this large number of RNA-seq experiments to search for evidence of unknown DMD isoforms that could potentially be upregulated to ameliorate the symptoms of DMD. In addition, we utilize DMD as an example of how diseases diagnosis could proceed using RNA-sequencing data by comparison to a broad cohort of RNA-seq samples.

Authors: Richard T Wang^1,2, Stanley F Nelson^1,2,3

¹Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

²Center for Duchenne Muscular Dystrophy, University of California Los Angeles, Los Angeles, CA, USA

³Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA