Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00100383" target="_blank" >RIV/00216224:14740/17:00100383 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/srep45494.pdf" target="_blank" >https://www.nature.com/articles/srep45494.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep45494" target="_blank" >10.1038/srep45494</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs

Popis výsledku v původním jazyce

Combining genome- wide mapping of SNP- rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome.We summed up the differentially methylated " expression neighbors" of genes that fall into one of 108 distinct schizophrenia- associated loci with high number of SNPs.Surprisingly, the number of expression neighbors of the genes in these loci were 35 times higher for the positively correlating genes (32 times higher for the negatively correlating ones) than for the rest of the similar to 16000 genes.While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia- related important genes with a high degree of connectedness (e.g.MOBP, SYNGR1 and DGCR6), validating our approach.Both the most connected positive and negative hubs affected synapse- related genes the most, supporting the synaptic origin of schizophrenia.At least half of the top genes in both the correlating and anti- correlating categories are cancer- related, including oncogenes (RRAS and ALDOA), providing further insight into the observed inverse relationship between the two diseases.

Název v anglickém jazyce

Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs

Popis výsledku anglicky

Combining genome- wide mapping of SNP- rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome.We summed up the differentially methylated " expression neighbors" of genes that fall into one of 108 distinct schizophrenia- associated loci with high number of SNPs.Surprisingly, the number of expression neighbors of the genes in these loci were 35 times higher for the positively correlating genes (32 times higher for the negatively correlating ones) than for the rest of the similar to 16000 genes.While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia- related important genes with a high degree of connectedness (e.g.MOBP, SYNGR1 and DGCR6), validating our approach.Both the most connected positive and negative hubs affected synapse- related genes the most, supporting the synaptic origin of schizophrenia.At least half of the top genes in both the correlating and anti- correlating categories are cancer- related, including oncogenes (RRAS and ALDOA), providing further insight into the observed inverse relationship between the two diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/ED1.1.00%2F02.0068" target="_blank" >ED1.1.00/02.0068: CEITEC - central european institute of technology</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

45494

Kód UT WoS článku

000398602500001

EID výsledku v databázi Scopus

2-s2.0-85017094765