Long Read Genome Sequencing Elucidates Diverse Functional Consequences of Structural and Repeat Variation in Autism.

ABSTRACT: Long-read whole genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). Application of LR-WGS has potential to identify novel risk factors that contribute to autism spectrum disorder (ASD). We performed LR-WGS on 243 individuals from 63 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 29% and 38%, respectively, and enabled identification of novel exonic de novo germline and somatic SVs that were not detected previously with short read WGS. We observed complex SV patterns, including a previously undescribed class of nested duplication-deletion (DUP-DEL) events. Joint analysis of phased TRs and methylation data revealed that hy

SUBMITTER: Mortazavi M 

PROVIDER: S-EPMC12330410 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature