Long-read sequencing reveals genomic and epigenomic variation in the dark genome of human Alzheimer's disease.

ABSTRACT:

Introduction

Faulty DNA repair and epigenetic regulation contribute to neurodegeneration in Alzheimer's disease. Long-read sequencing enables analysis of "dark regions" that are difficult to study via traditional sequencing methodologies.

Methods

Using nanopore whole-genome DNA sequencing of post mortem brain from early- and late- stage Alzheimer's disease cases and controls, we analyzed retrotransposition, non-allelic homologous recombination (NAHR), structural variation, and DNA methylation within repetitive regions.

Results

Retrotransposon insertions and NAHR were enriched in centromeric/pericentromeric and ribosomal DNA (rDNA) in the aged brain. Putatively somatic AluY retrotransposon insertions trended upward in late-stage disease. Enrichment of NAHR between repe

SUBMITTER: Ramirez P 

PROVIDER: S-EPMC12616516 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature