Center for Alzheimer's and Related Dementias (CARD): 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 acquiring samples of interest with significant WGS, clinical, pathological, or omics data available. To better understand the genetics of diverse populations, we have prioritized samples from underrepresented groups. Through this effort, we have fully sequenced around 2300 human frontal cortex brain samples across four cohorts, including the North American Brain Expression Consortium study (European ancestry), the Human Brain Collection Core (African ancestry), Universidad de Antioquia’s Brain Bank of the Neuroscience Group of Antioquia (Latin American ancestry), and the Religious Orders Study/Memory and Aging Project study (European ancestry). From these efforts, we have published a pre-print and released the first data release on anvil, of approximately 350 control samples. We have shared our current brain, blood, and frozen cell extraction wet-lab protocols on the widely-used and easily accessible protocol-sharing platform Protocols.IO, which have received over 4000 views combined. Additionally, we have developed a new computational tool named Napu, which was recently published in Nature Methods. Napu is now being widely used in the community, particularly in other large-scale long-read initiatives such as the 1000G long-read project. The data used for this tool development has been made publicly available as a reference via the Alzheimer’s Disease WorkBench and the AnVIL (NHGRI. To empower the community interested in long-read sequencing, all code and benchmarks have been made public.