Long-read DNA sequencing of Alzheimers Disease and Related Dementias cases

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

We have finalized DNA isolation protocols from brain tissue, blood, and induced pluripotent stem cells. We have begun to acquire samples of interest with significant WGS, clinical, pathological, or omics data available. We have prioritized samples from underrepresented populations to better understand genetics of diverse populations. We have fully sequenced roughly 200 human frontal cortex brain samples with an average coverage of 30X and an average N50 of 30kb. We have identified platforms for digital storage and hosting of our long-read sequencing datasets. We have shared the current brain, blood, and frozen cell extractions protocols on the widely-used and easily-accessible protocol sharing platform Protocols.IO, which have received over 2000 views combined. A manuscript on these efforts has also been accepted to Nature Methods. In addition, the data has been widely shared as a public reference via the Alzheimers Disease Work Bench and NIHGRIs the AnVIL. To help empower the community interested in long read, all code and benchmarks have been made public. Kolmogorov M, Billingsley KJ, Mastoras M, Meredith M, Monlong J, Lorig-Roach R, Asri M, Alvarez Jerez P, Malik L, Dewan R, Reed X, Genner RM, Daida K, Behera S, Shafin K, Pesout T, Prabakaran J, Carnevali P; North American Brain Expression Consortium (NABEC); Yang J, Rhie A, Scholz SW, Traynor BJ, Miga KH, Jain M, Timp W, Phillippy AM, Chaisson M, Sedlazeck FJ, Blauwendraat C, Paten B. Scalable Nanopore sequencing of human genomes provides a comprehensive view of haplotype-resolved variation and methylation. bioRxiv Preprint, accepted to Nature Methods. 2023 Apr 5:2023.01.12.523790. doi: 10.1101/2023.01.12.523790. PMID: 36711673; PMCID: PMC9882142.