Identification and validation of expression quantitative trait loci (eQTLs) in discrete cell types across human brain development

  • Awarded: 2021
  • Award Type: Director
  • Award #: 736706

Functional genomic analyses of the developing human brain have revealed highly dynamic spatiotemporal patterns of gene expression and epigenetic changes during prenatal and early postnatal development and across brain regions. Disruptions of these developmentally dynamic processes have been implicated by numerous complementary analyses in the etiology of multiple neurodevelopmental and psychiatric disorders.

Expression quantitative trait loci (eQTLs), along with splicing quantitative trait loci (sQTLs) and structural variant quantitative trait loci (svQTLs), are genomic variants that differ between individuals, with these differences correlating with functional changes to gene expression or splicing behavior. Many of these QTLs show specificity to tissues, brain regions, developmental stages or cell types, and they show a proportion overlap with known genetic risk factors of human disorders.

In the current project, Nenad Sestan and Stephan Sanders’ labs plan to pursue three integrated aims, including whole-genome sequencing and both bulk tissue and single-nuclei RNA sequencing of human brain tissue samples, to identify genomic variants (eQTL/sQTL/svQTLs) and patterns of gene expression and co-expression across development. In addition, they plan to apply novel computational tools to associate these QTLs with specific cell types and loci or genes implicated in neurodevelopmental and psychiatric disorders. By doing so, the researchers will augment and dramatically expand upon earlier efforts to understand QTLs and their roles in neural development, function and neurodevelopmental and psychiatric disorders.

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