Identification of genetic elements in metabolism by high-throughput mouse phenotyping

0486935 - ÚMG 2018 RIV GB eng J - Článek v odborném periodiku
Sedláček, Radislav … celkem 61 autorů
Identification of genetic elements in metabolism by high-throughput mouse phenotyping.
Nature Communications. Roč. 9, zima (2018), č. článku 288. E-ISSN 2041-1723
Institucionální podpora: RVO:68378050
Klíčová slova: Insulin-resistance * Diabetes-mellitus * Glycemic traits * Variants * Architecture * Association * Consortiuj * Pathways * Disease * Biology
Obor OECD: Genetics and heredity (medical genetics to be 3)
Impakt faktor: 11.878, rok: 2018

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of coregulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.
Trvalý link: http://hdl.handle.net/11104/0281640