Independent splice-creating mutations in an intron of the COL6A1 in two patients with collagen VI myopathyBERYL CUMMINGS, HARVARD UNIVERSITYRNA sequencing (RNA-seq) of affected tissue can be used to discover mutations likely responsible for Mendelian disorders, according to researchers from the Broad Institute of MIT and Harvard and their colleagues. A team led by Daniel MacArthur of the Broad Institute used RNA-seq on skeletal muscle biopsies from patients with rare, undiagnosed genetic disorders to uncover novel disease-causing mutations that are not easily identified with DNA sequencing, such as pathogenic splice site variants. The study, published in Science Translational Medicine today (April 19), is the largest-to-date application of transcriptome sequencing to a cohort of patients with undiagnosed diseases to identify previously unknown mutations associated with inherited disorders.
“This is a really great study that demonstrates beautifully the use of RNA sequencing in discovering and charactering relevant human disease mutations,” said Tuuli Lappalainen of the New York Genome Center, who collaborates with some of the coauthors in the Genotype-Tissue Expression (GTEx) Consortium but was not involved in the present study. “This is the first really compelling example of how well this can work.”
“There has been a huge step forward in how quickly we can do DNA sequencing to diagnose rare genetic diseases. But that approach still cannot identify the relevant mutation in about 60 percent of cases,” Jeffrey Barrett of the Wellcome Trust Sanger Institute who was not involved in the work told The Scientist. “This new paper is a really nice ...
