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Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Abstract: Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding 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, interrogating 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 transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/.

 Fuente: Nature Communications 11, 1041 (2020).

 Editorial: Nature Publishing Group

 Fecha de publicación: 01/02/2020

 Nº de páginas: 16

 Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41467-020-14483-x

 ISSN: 2041-1723

 Url de la publicación: https://doi.org/10.1038/s41467-020-14483-x

Autoría

GUELFI, SEBASTIAN

KARISHMA D'SA

BOTÍA, JUAN A.

VANDROVCOVA, JANA

REYNOLDS, REGINA H.

ZHANG, DAVID

TRABZUNI, DANIAH

COLLADO-TORRES, LEONARDO

THOMASON, ANDREW

QUIJADA LEYTON, PEDRO

GAGLIANO TALIUN, SARAH A.

NALLS, MIKE A.

INTERNATIONAL PARKINSON'S DISEASE GENOMICS CONSORTIUM (IPDGC)

UK BRAIN EXPRESSION CONSORTIUM (UKBEC)

SMALL, KERRIN S.

SMITH, COLIN

RAMASAMY, ADAIKALAVAN

HARDY, JOHN

WEALE, MICHAEL E.