Gene expression in the human brain

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

We have focused on developing datasets for gene expression to study the effects of mutations in the genes associated with age-associated neurodegeneration. 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 Alzheimer's, Frontotemporal dementia. and Parkinson's disease) or other phenotype, has a proximal biological effect on gene expression. This work has been used across several projects in LNG to nominate genes and variants for novel loci associated with disease. We have also added single cell chromatin accessibility measures using ATAC-seq as a measure of epigenetic status in cells. This has been applied to our studies of the LRRK2 locus where we found that patterns of chromatin accessibility vary between major cell types of the brain with specific areas of open chromatin found only in microglia. We have extended this work to look across different brain regions associated with various neurodegenerative conditions and have found that there are enrichments for differing diseases across many cell types and loci.