A simple blood test may help diagnose and develop therapies for the most common genetic form of ALS. The strategy, proposed by a research team led by the University of Florida’s Maurice Swanson in Gainesville, screens for the presence of a key intron in transcripts of the C9orf72 gene.
The approach is based on RNA-seq analysis, which suggests that GC-rich repeat expansions, linked to ALS, interfere with mRNA splicing, leading to the retention of the first intron in the C9orf72 ALS gene (see also Niblock et al., 2016).
The strategy is potentially a key alternative to existing PCR-based approaches for detecting repeat expansions in larger populations including in genome-wide association studies (GWAS) and in clinical trials.
The approach builds on previous studies, which found that repeat-rich C9orf72 RNAs “escape” the nucleus via a SRSF1-based mechanism (see July 2017 news; Niblock et al., 2016; Hautbergue et al., 2017).
A new approach may provide a key alternative to repeat-primed PCR to detect C9orf72 repeat expansions in large cohorts. The RNA-seq-based strategy, in part, uses IRFinder to screen for intron retention (Middleton et al., 2017). [Courtesy of Sznajder et al., 2018, Proceedings of the National Academy of Sciences.]
Source – ALS Research Forum