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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00486935" target="_blank" >RIV/68378050:_____/18:00486935 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41467-017-01995-2" target="_blank" >http://dx.doi.org/10.1038/s41467-017-01995-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-01995-2" target="_blank" >10.1038/s41467-017-01995-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10620 - Other biological topics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

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Svazek periodika

9

Číslo periodika v rámci svazku

zima

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

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Kód UT WoS článku

000422745800023

EID výsledku v databázi Scopus

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