Genetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource.

TitleGenetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource.
Publication TypeJournal Article
Year of Publication2017
AuthorsKeogh, MJ, Wei, W, Wilson, I, Coxhead, J, Ryan, S, Rollinson, S, Griffin, H, Kurzawa-Akanbi, M, Santibanez-Koref, M, Talbot, K, Turner, MR, McKenzie, C-A, Troakes, C, Attems, J, Smith, C, Sarraj, SAl, Morris, CM, Ansorge, O, Pickering-Brown, S, Ironside, JW, Chinnery, PF
JournalGenome Res
Volume27
Issue1
Pagination165-173
Date Published2017 Jan
ISSN1549-5469
Abstract

Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368). Genomic DNA was extracted from brain tissue in all cases before exome sequencing (Illumina Nextera 62 Mb capture) with variants called by FreeBayes; copy number variant (CNV) analysis (Illumina HumanOmniExpress-12 BeadChip); C9orf72 repeat expansion detection; and APOE genotyping. Established or likely pathogenic heterozygous, compound heterozygous, or homozygous variants, together with the C9orf72 hexanucleotide repeat expansions and a copy number gain of APP, were found in 61 brains. In addition to known risk alleles in 349 brains (23.9% of 1461 undergoing exome sequencing), we saw an association between rare variants in GRN and DLB. Rare CNVs were found in

DOI10.1101/gr.210609.116
Alternate JournalGenome Res.
Citation Key10.1101/gr.210609.116
PubMed ID28003435
PubMed Central IDPMC5204341
Grant ListMR/K01014X/1 / / Medical Research Council / United Kingdom
G1100540 / / Medical Research Council / United Kingdom
MR/L016400/1 / / Medical Research Council / United Kingdom
G0900652 / / Medical Research Council / United Kingdom
G0502157 / / Medical Research Council / United Kingdom
G0400074 / / Medical Research Council / United Kingdom
G0600953 / / Medical Research Council / United Kingdom