Genomics at cellular resolution: insights into cognitive disorders and their evolution.

Abstract

High-throughput genomic sequencing approaches have held the promise of understanding and ultimately leading to treatments for cognitive disorders such as autism spectrum disorders, schizophrenia and Alzheimer's disease. Although significant progress has been made into identifying genetic variants associated with these diseases, these studies have also uncovered that these disorders are mostly genetically complex and thus challenging to model in non-human systems. Improvements in such models might benefit from understanding the evolution of the human genome and how such modifications have affected brain development and function. The intersection of genome-wide variant information with cell-type-specific expression and epigenetic information will further assist in resolving the contribution of particular cell types in evolution or disease. For example, the role of non-neuronal cells in brain evolution and cognitive disorders has gone mostly underappreciated until the recent availability of single-cell transcriptomic approaches. In this review, we discuss recent studies that carry out cell-type-specific assessments of gene expression in brain tissue across primates and between healthy and disease populations. The emerging results from these studies are beginning to elucidate how specific cell types in the evolved human brain are contributing to cognitive disorders.