OMIA 002217-9823 : Hyperphagia leading to hepatic steatosis in Sus scrofa

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 618406 (trait) , 155541 (gene)

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Species-specific description: Kim et al. (2000): "The melanocortin-4 receptor gene (MC4R) has been implicated in the regulation of feeding behavior and body weight in humans and mice. We have studied MC4R as a candidate gene for the control of economically important growth and performance traits in the pig. A missense mutation was identified in a region highly conserved among melanocortin receptor (MCR) genes. To determine whether there was an association of this MC4R polymorphism with phenotypic variation, we tested the mutation in a large number of individual animals from several different pig lines. Analyses of growth and performance test records showed significant associations of MC4R genotypes with backfat and growth rate in a number of lines as well as feed intake overall."

Hao et al. (2019) created "MC4R biallelic knockout pigs using CRISPR/Cas9" (Hao et al., 2019). This work concerns a genetically-modified organism (GMO).

Clinical features: Hao et al. (2019) concluded "that deletion of MC4R results in hyperphagia and increased body fat, ultimately leading to hepatic steatosis without atherogenic diet."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MC4R melanocortin 4 receptor Sus scrofa 1 NC_010443.5 (160772013..160774124) MC4R 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
fatness, growth, feed intake MC4R missense Sscrofa11.1 1 g.160773437G>A p.(D298N) rs81219178 rs81219178 2000 10656927 Variant coordinates updated based on Johnsson and Jungnickel (2021)

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.
2021 Johnsson, M., Jungnickel, M.K. :
Evidence for and localization of proposed causative variants in cattle and pig genomes. Genet Sel Evol 53:67, 2021. Pubmed reference: 34461824. DOI: 10.1186/s12711-021-00662-x.
2020 Zhang, J., Li, J., Wu, C., Hu, Z., An, L., Wan, Y., Fang, C., Zhang, X., Li, J., Wang, Y. :
The Asp298Asn polymorphism of melanocortin-4 receptor (MC4R) in pigs: evidence for its potential effects on MC4R constitutive activity and cell surface expression. Anim Genet :, 2020. Pubmed reference: 32738077. DOI: 10.1111/age.12986.
2019 Hao, H., Lin, R., Li, Z., Shi, W., Huang, T., Niu, J., Han, J., Li, Q. :
MC4R deficiency in pigs results in hyperphagia and ultimately hepatic steatosis without high-fat diet. Biochem Biophys Res Commun :, 2019. Pubmed reference: 31629472. DOI: 10.1016/j.bbrc.2019.08.016.
2000 Kim, K.S., Larsen, N., Short, T., Plastow, G., Rothschild, M.F. :
A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits. Mamm Genome 11:131-5, 2000. Pubmed reference: 10656927.

Edit History


  • Created by Frank Nicholas on 22 Oct 2019
  • Changed by Frank Nicholas on 22 Oct 2019
  • Changed by Imke Tammen2 on 03 Sep 2021