Wild-type C9orf72 expression is a genetic modifier of C9-ALS survival - PubMed
4 hours ago
- #C9orf72
- #ALS
- #genetic modifiers
- Amyotrophic lateral sclerosis (ALS) is highly heritable but lacks identifiable genetic causes in most cases.
- A multi-omic QTL atlas was created using 594 human motor neuron lines (522 ALS patients, 72 controls).
- Common and rare variants on the wild-type C9orf72 allele form regulatory haplotypes influencing expression levels.
- C9-ALS patients were stratified into four subgroups with different survival trajectories based on C9orf72 expression.
- Ultra-rare intronic variants create cryptic exons and structural variants in ALS genes, aiding in molecular diagnosis.
- QTL mapping in patient-derived motor neurons reveals regulatory modifiers and hidden pathogenic events in ALS.