Journal Article DKFZ-2020-02396

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png
A complementary study approach unravels novel players in the pathoetiology of Hirschsprung disease.

 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;

2020
Public Library of Science San Francisco, Calif.

PLoS Genetics 16(11), e1009106 - () [10.1371/journal.pgen.1009106]
 GO

This record in other databases:  

Please use a persistent id in citations: doi:

Abstract: Hirschsprung disease (HSCR, OMIM 142623) involves congenital intestinal obstruction caused by dysfunction of neural crest cells and their progeny during enteric nervous system (ENS) development. HSCR is a multifactorial disorder; pathogenetic variants accounting for disease phenotype are identified only in a minority of cases, and the identification of novel disease-relevant genes remains challenging. In order to identify and to validate a potential disease-causing relevance of novel HSCR candidate genes, we established a complementary study approach, combining whole exome sequencing (WES) with transcriptome analysis of murine embryonic ENS-related tissues, literature and database searches, in silico network analyses, and functional readouts using candidate gene-specific genome-edited cell clones. WES datasets of two patients with HSCR and their non-affected parents were analysed, and four novel HSCR candidate genes could be identified: ATP7A, SREBF1, ABCD1 and PIAS2. Further rare variants in these genes were identified in additional HSCR patients, suggesting disease relevance. Transcriptomics revealed that these genes are expressed in embryonic and fetal gastrointestinal tissues. Knockout of these genes in neuronal cells demonstrated impaired cell differentiation, proliferation and/or survival. Our approach identified and validated candidate HSCR genes and provided further insight into the underlying pathomechanisms of HSCR.

Classification:

Contributing Institute(s):
  1. B080 Theoretische Bioinformatik (B080)
  2. W110 Microarray Unit (W110)
Research Program(s):
  1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020
Database coverage:
Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; Article Processing Charges ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record
Click to display QR Code for this record

The record appears in these collections:
Document types > Articles > Journal Article
Public records
Publications database

 Record created 2020-11-09, last modified 2024-02-29



Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)