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.

Genetic engineering: Unknown
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."

Breed: 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

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002716-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

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.

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  • Created by Imke Tammen2 on 09 Jun 2023
  • Changed by Imke Tammen2 on 09 Jun 2023