Gene expression in the human brain

National Institute On Aging

Investigators

Linked publications & trials

Abstract

We have focused on developing datasets for gene expression to study the effects of mutations in the genes associated with neurodegeneration including Alzheimers disease. Using RNA-Seq allows us to apply a standard set of methods to a variety of model systems. Using this approach we have contributed to a number of different studies. One of the most interesting areas is in the application to the human brain, where we have a large series of brains with information on both genetic variability and gene expression. Our data has been used in many studies to determine whether a nominated genetic variant associated with a given disease (such as Alzheimers) or other phenotype, has a proximal biological effect on gene expression. We have moved our approach towards single cell genomics, generating a large dataset from a subset of donors with extensive genotypic information. This data has been used already to evaluate genes associated with multiple neurodegenerative diseases. Additionally, we have nominated expression as a quantitative trait for a specific Parkinson's disease gene to be restricted to microglia. Finally, we have extended these approaches to look at chromatin accessibility using single-nuclear Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) across multiple brain regions, which we plan to map to neurodegeneration-associated genetic variation.