Much of the genetic basis of Alzheimer's disease and related dementias (AD/ADRD) is still unexplained, and some of the answers may sit in parts of the genome that standard sequencing cannot read. Short-read sequencing often fails to resolve large structural variants, repeat expansions, and complex genomic regions, so variants that could drive disease go undetected. To close this gap, researchers at the NIH Center for Alzheimer's and Related Dementias (CARD) have built one of the largest long-read whole-genome sequencing resources in human brain tissue.
In this webinar, brought to you by Oxford Nanopore, Kimberley Billingsley, the head of the Translational Neurogenomics Group at CARD, will present discoveries of AD/ADRD-relevant mutations made possible by long-read sequencing. She will cover how haplotype-resolved methylation at key loci such as APOE points to new layers of epigenetic regulation and how the team extended this work to long-read RNA sequencing of brain tissue, which enables isoform-level transcriptomic analysis alongside the genomic and epigenetic data.
Topics to be covered:
- How a large-scale long-read whole-genome sequencing resource was built across multiple postmortem brain cohorts
- How long reads reveal structural variants and repeat expansions linked to Alzheimer's disease and related dementias
- What haplotype-specific methylation at loci such as APOE shows about epigenetic regulation that short reads can't reach
- How long-read RNA sequencing adds isoform-resolved transcriptomic data to genomic and epigenetic analyses of the brain
- An introduction to Oxford Nanopore by Walaa Mohamed