File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)

Article: RET and NRG1 interplay in Hirschsprung disease

TitleRET and NRG1 interplay in Hirschsprung disease
Authors
Issue Date2013
Citation
Human Genetics, 2013, v. 132, n. 5, p. 591-600 How to Cite?
AbstractHirschsprung disease (HSCR, aganglionic megacolon) is a complex genetic disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1. Importantly, RVs in the CDS of these two genes are also associated with the disorder. To assess independent and joint effects between the different types of RET and NRG1 variants identified in HSCR patients, we used 254 Chinese sporadic HSCR patients and 143 ethnically matched controls for whom the RET and/or NRG1 variants genotypes (rare and common) were available. Four genetic risk factors were defined and interaction effects were modeled using conditional logistic regression analyses and pair-wise Kendall correlations. Our analysis revealed a joint effect of RET CVs with RET RVs, NRG1 CVs or NRG1 RVs. To assess whether the genetic interaction translated into functional interaction, mouse neural crest cells (NCCs; enteric neuron precursors) isolated from embryonic guts were treated with NRG1 (ErbB2 ligand) or/and GDNF (Ret ligand) and monitored during the subsequent neural differentiation process. Nrg1 inhibited the Gdnf-induced neuronal differentiation and Gdnf negatively regulated Nrg1-signaling by down-regulating the expression of its receptor, ErbB2. This preliminary data suggest that the balance neurogenesis/gliogenesis is critical for ENS development. © 2013 Springer-Verlag Berlin Heidelberg.
Persistent Identifierhttp://hdl.handle.net/10722/220750
ISSN
2015 Impact Factor: 5.138
2015 SCImago Journal Rankings: 2.931
Errata

 

DC FieldValueLanguage
dc.contributor.authorGui, Hongsheng-
dc.contributor.authorTang, Wai Kiu-
dc.contributor.authorSo, Man Ting-
dc.contributor.authorProitsi, Petroola-
dc.contributor.authorSham, Pak C.-
dc.contributor.authorTam, Paul K.-
dc.contributor.authorNgan, Elly S W-
dc.contributor.authorCherny, Stacey S.-
dc.contributor.authorGarcia-Barceló, Maria Mercè-
dc.date.accessioned2015-10-16T06:50:26Z-
dc.date.available2015-10-16T06:50:26Z-
dc.date.issued2013-
dc.identifier.citationHuman Genetics, 2013, v. 132, n. 5, p. 591-600-
dc.identifier.issn0340-6717-
dc.identifier.urihttp://hdl.handle.net/10722/220750-
dc.description.abstractHirschsprung disease (HSCR, aganglionic megacolon) is a complex genetic disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1. Importantly, RVs in the CDS of these two genes are also associated with the disorder. To assess independent and joint effects between the different types of RET and NRG1 variants identified in HSCR patients, we used 254 Chinese sporadic HSCR patients and 143 ethnically matched controls for whom the RET and/or NRG1 variants genotypes (rare and common) were available. Four genetic risk factors were defined and interaction effects were modeled using conditional logistic regression analyses and pair-wise Kendall correlations. Our analysis revealed a joint effect of RET CVs with RET RVs, NRG1 CVs or NRG1 RVs. To assess whether the genetic interaction translated into functional interaction, mouse neural crest cells (NCCs; enteric neuron precursors) isolated from embryonic guts were treated with NRG1 (ErbB2 ligand) or/and GDNF (Ret ligand) and monitored during the subsequent neural differentiation process. Nrg1 inhibited the Gdnf-induced neuronal differentiation and Gdnf negatively regulated Nrg1-signaling by down-regulating the expression of its receptor, ErbB2. This preliminary data suggest that the balance neurogenesis/gliogenesis is critical for ENS development. © 2013 Springer-Verlag Berlin Heidelberg.-
dc.languageeng-
dc.relation.ispartofHuman Genetics-
dc.titleRET and NRG1 interplay in Hirschsprung disease-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00439-013-1272-9-
dc.identifier.pmid23400839-
dc.identifier.scopuseid_2-s2.0-84876489678-
dc.identifier.hkuros214476-
dc.identifier.volume132-
dc.identifier.issue5-
dc.identifier.spage591-
dc.identifier.epage600-
dc.identifier.eissn1432-1203-
dc.relation.erratumdoi:10.1007/s00439-014-1429-1-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats