RGD Reference Report - Identification of genetic loci affecting the severity of symptoms of Hirschsprung disease in rats carrying Ednrbsl mutations by quantitative trait locus analysis. - Rat Genome Database

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Identification of genetic loci affecting the severity of symptoms of Hirschsprung disease in rats carrying Ednrbsl mutations by quantitative trait locus analysis.

Authors: Huang, J  Dang, R  Torigoe, D  Lei, C  Lan, X  Chen, H  Sasaki, N  Wang, J  Agui, T 
Citation: Huang J, etal., PLoS One. 2015 Mar 19;10(3):e0122068. doi: 10.1371/journal.pone.0122068. eCollection 2015.
RGD ID: 10402048
Pubmed: (View Article at PubMed) PMID:25790447
DOI: Full-text: DOI:10.1371/journal.pone.0122068

Hirschsprung's disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Gdil2  (Gastrointestinal dilation QTL 2)

Objects referenced in this article
0 AR-Ednrbsl/Hkv Aganglionosis rat All species
0 F344.AR-Ednrbsl/Hkv Aganglionosis rat All species
0 Gdil1 Gastrointestinal dilation QTL 1 All species
0 LE/Hkv.AR-Ednrbsl Aganglionosis rat All species

Additional Information