Long-read genome sequencing improves detection and functional interpretation of structural and repeat variants in autism - PubMed
a day ago
- #structural variants
- #long-read sequencing
- #autism
- Long-read whole-genome sequencing (LR-WGS) enhances detection of structural variants (SVs) and tandem repeats (TRs) in autism spectrum disorder (ASD).
- LR-WGS on 267 individuals from 63 ASD families increased detection of gene-disrupting SVs by 33% and TRs by 38%.
- Novel exonic de novo germline and somatic SVs were identified, including complex nested duplication-deletion events.
- Joint analysis of phased genetic variation and DNA methylation revealed deletions of imprinted genes and effects of intermediate CGG repeats on FMR1 promoter methylation.
- Rare SVs, TRs, and damaging SNVs accounted for 7.4% of ASD heritability (95% CI, 2.7%-17%).
- LR-WGS resolves complex genetic variation and its functional, regulatory effects in a single assay.