Artículo
Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information
Autor/es | Guelfi, Sebastian
D’Sa, Karishma Botía, Juan A. Vandrovcova, Jana Reynolds, Regina H. Zhang, David Mir Rivera, Pablo Labrador-Espinosa, Miguel Á. Periñán Tocino, María Teresa |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2020-02-25 |
Fecha de depósito | 2023-03-31 |
Publicado en |
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Resumen | Genome-wide association studies have generated an increasing number of common genetic
variants associated with neurological and psychiatric disease risk. An improved under-
standing of the genetic control of gene expression ... Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved under- standing of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, inter- rogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain tran- scriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/. |
Agencias financiadoras | Alzheimer's Research UK Leonard Wolfson Doctoral Training Fellowship in Neurodegeneration MRC UK Medical Research Council (MRC) MR/N008324/1 |
Identificador del proyecto | ARUK-PhD2014-16
MR/T04604X/1 UKDRI-3003 MR/N026004/1 MR/L023784/2 MR/K01417X/1 UKDRI-1009 MR/S006753/1 |
Cita | Guelfi, S., D’Sa, K., Botía, J.A., Vandrovcova, J., Reynolds, R.H., Zhang, D.,...,Periñán Tocino, M.T. (2020). Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information. Nature Communications, 11 (1). https://doi.org/10.1038/s41467-020-14483-x. |
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