Systematic Analysis of Genetic Mosaicism in FTD/ALS Brains
Abstract
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two closely related neurodegenerative diseases with TAR DNA-binding protein 43 (TDP-43) inclusions as a common pathological hallmark. They are characterized as age-related neurodegeneration, yet the mechanisms by which age and genetic risk interact, as well as the ultimate cause of neuronal loss, remains murky. Clinical features of FTD/ALS, including focal onset, stereotyped patterns of spread, and increased risk due to smoking, have suggested to some a role of somatic mutations as causative for some unexplained cases of FTD/ALS. Our major goal is to reveal the potential roles of genetic mosaicism in the etiology and progression of FTD/ALS. Our study identifies clonal and non-clonal somatic mutations in FTD/ALS brains using ultra-deep targeted sequencing and single-cell whole genome sequencing. In the last funding period, we have collected human postmortem brain tissues from several brain banks. We have also tested the targeted panel sequencing and single-cell L1 targeted sequencing approaches and gotten great performance from testing experiments. In the next funding period, we will apply these approaches to all collected human postmortem brain tissues to systematically examine the burden and pattern of various types of somatic mutations in FTD/ALS brains.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2022
- Accession Number
- AD1169468
Entities
People
- Zinan Zhou