OMIA:002716-9615 : Megaoesophagus, MCHR2-related in Canis lupus familiaris (dog)
Categories: Digestive / alimentary phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 606111 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2022
Species-specific name: congenital idiopathic megaesophagus, CIM
Species-specific symbol: CIM
Mapping: By conducting a GWAS on 19 affected and 177 control German Shepherd dogs, each genotyped with the Affymetrix v2 canine SNP chip (Yielding 48,415 SNPs for the analysis), Tsai et al. (2012) highlighted a 4.7Mb region on chromosome CFA12.
Bell et al. (2022) also highlighted a region in CFA12: "A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility." It is not evident whether this region overlaps the region highlighted by Tsai et al. (2012).
Molecular basis: Bell et al. (2022): "Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM [Congenital idiopathic megaesophagus] (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Prevalence: Bell et al. (2022) reported "that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage".
Control: Bell et al. (2022): "Together, sex and the MCHR2 repeat sequence accurately predict affection status in over 75% of dogs, and a genetic test is now available to facilitate breeding decisions aimed at reducing disease incidence."
German Shepherd Dog (Dog) (VBO_0200577).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MCHR2||melanin-concentrating hormone receptor 2||Canis lupus familiaris||12||NC_051816.1 (58932320..58907909)||MCHR2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1437||German Shepherd Dog (Dog)||Congenital idiopathic megaesophagus||MCHR2||repeat variation||Naturally occurring variant||CanFam3.1||12||Bell et al. (2022): "Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk".||2022||35271580|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Bell, S.M., Evans, J.M., Evans, K.M., Tsai, K.L., Noorai, R.E., Famula, T.R., Holle, D.M., Clark, L.A. :|
|Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2. PLoS Genet 18:e1010044, 2022. Pubmed reference: 35271580. DOI: 10.1371/journal.pgen.1010044.|
|2019||Haines, J.M. :|
|Survey of owners on population characteristics, diagnosis, and environmental, health, and disease associations in dogs with megaesophagus. Res Vet Sci 123:1-6, 2019. Pubmed reference: 30543946. DOI: 10.1016/j.rvsc.2018.11.026.|
|2012||Tsai, K.L., Noorai, R.E., Starr-Moss, A.N., Quignon, P., Rinz, C.J., Ostrander, E.A., Steiner, J.M., Murphy, K.E., Clark, L.A. :|
|Genome-wide association studies for multiple diseases of the German Shepherd Dog. Mamm Genome 23:203-11, 2012. Pubmed reference: 22105877. DOI: 10.1007/s00335-011-9376-9.|
- Created by Imke Tammen2 on 09 Jun 2023
- Changed by Imke Tammen2 on 09 Jun 2023