2026-03-09 カリフォルニア大学サンディエゴ校（UCSD）
＜関連情報＞
- https://today.ucsd.edu/story/long-read-genome-sequencing-uncovers-new-autism-gene-variants
- https://www.cell.com/cell-genomics/fulltext/S2666-979X(26)00048-0
ロングリードゲノムシーケンシングは、自閉症における構造的および反復変異の検出と機能的解釈を改善します Long-read genome sequencing improves detection and functional interpretation of structural and repeat variants in autism
Milad Mortazavi ∙ James Guevara ∙ Joshua Diaz ∙ … ∙ Melissa Gymrek ∙ Abraham A. Palmer ∙ Jonathan Sebat
Cell Genomics Published:March 9, 2026
DOI:https://doi.org/10.1016/j.xgen.2026.101186
Highlights
- Long-read WGS boosted SV/TR detection by 33%/38% and found novel de novo SVs
- A previously undescribed class of DUP-DEL complex structural variants was identified
- Joint SV/TR/methylation analysis revealed variants in imprinted genes and FMR1
- Rare variants (SVs, TRs, damaging SNVs) explain between 3% and 17% of ASD heritability
Summary
Long-read whole-genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). We performed LR-WGS on 267 individuals from 63 autism spectrum disorder (ASD) families and generated an integrated call set combining long- and short-read data. LR-WGS increased detection of gene-disrupting SVs and TRs by 33% and 38%, respectively, and enabled identification of novel exonic de novo germline and somatic SVs. We observed complex SV patterns, including a class of nested duplication-deletion events. By joint analysis of phased genetic variation and DNA methylation, we identified deletions of imprinted genes and demonstrated the effect of intermediate TR expansions (35–54 CGG) on the methylation of FMR1 promoter. Rare SVs, TRs, and damaging SNVs together accounted for 7.4% (95% confidence interval [CI], 2.7%–17%) of the heritability of ASD. These findings demonstrate how LR-WGS can resolve complex genetic variation and its functional consequences and regulatory effects in a single assay.
