OMIA:001529-9913 : Coat colour, dominant red in Bos taurus (taurine cattle)
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 601924 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2014
Species-specific name: Also known as Variant Red, Holstein dominant red; Haplotype HDR
Species-specific symbol: VR (Variant Red); HDR (Holstein Dominant Red)
History: This dominant trait was first reported by Leduc (2006) who, in the words of Dorshorst et al. (2015) reported that "In 1980, a female Holstein calf (HOCANF3541221, SURINAM SHEIK ROSABEL-RED) was born in Canada that displayed the typical red Holstein coat color phenotype . . . , but from parents that were not thought to carry either of the MC1R alleles associated with red color based on pedigree."
Inheritance: Dreger and Schmutz (2010) reported that "The variant red phenotype in Holstein cattle is indistinguishable from the traditional e/e recessive red phenotype caused by a mutation in melanocortin 1 receptor [OMIA 001199-9913], but is inherited as a dominant trait in relation to black".
Dorshorst et al. (2015) propose "that the Dominant Red locus is designated DR with two alleles, the derivative allele DR^DR and the ancestral or wild-type allele DR^+".
Mapping: Dreger and Schmutz (2010) excluded linkage of this trait with polymorphisms in some of the common coat-colour genes, namely melanocortin 1 receptor (MC1R), agouti signalling protein (ASIP), attractin (ATRN) and melatonin receptor 1A (MTNR1A). However, linkage with microsatellites near, and SNPs within the 5' UTR of, another comparative candidate coat-colour gene (beta-defensin 103; DEFB103), located on chromosome BTA27, was detected.
Using SNP-chip genotypes of Holsteins from the shared national resource maintained by the Council on Dairy Cattle Breeding (CDCB; Reynoldsburg, Ohio), Lawlor et al. (2013) identified a haplotype at 8-12 Mb on chromosome BTA3 that co-segregates with this trait. While this results appears to contradict the earlier linkage result, it is known that there are many defensin genes/pseudogenes scattered throughout the bovine genome, and it is possible that the earlier results actually involved a defensin-like sequence on BTA3.
Using "31 cases and 36 control relatives", each genotyped with the Illumina BovineSNP50 chip, Capitan et al. (2014)/Bourneuf et al. (2017) confirmed and detaileded the location of this trait to a 4.6Mb region on chromosome BTA3: 7,906,099-12,475,989.
Dorshorst et al. (2015) used linkage mapping and GWAS to also confirm the BTA3 map location.
Molecular basis: By comparing whole-genome sequence of a small number of Holsteins having the trait, with sequence data from hundreds of control animals, Capitan et al. (2014) confirmed the mapping results of Lawlor et al. (2014) and identified the causal mutation as a de novo variant BTA3 g.C9479761T, which corresponds to a missense mutation p.R160C in the COPA gene that encodes coatomer protein complex, subunit alpha.
By whole-genome sequencing of a Dominant Red heterozygote, Dorshorst et al. (2015) confirmed this causal mutation (c.478C>T; p.Arg160Cys).
The results of Capitan et al. (2014) were formally published by Bourneuf et al. (2017).
Have human generated variants been created, e.g. through genetic engineering and gene editing
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|COPA||coatomer protein complex subunit alpha||Bos taurus||3||NC_037330.1 (9350619..9394691)||COPA||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|
|215||Holstein (black and white) (Cattle)||Dominant red||COPA||DR^DR||missense||Naturally occurring variant||ARS-UCD1.2||3||g.9361962C>T||c.478C>T||p.(R160C)||rs3423151160||2017||28904385||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2017||Bourneuf, E., Otz, P., Pausch, H., Jagannathan, V., Michot, P., Grohs, C., Piton, G., Ammermüller, S., Deloche, M.C., Fritz, S., Leclerc, H., Péchoux, C., Boukadiri, A., Hozé, C., Saintilan, R., Créchet, F., Mosca, M., Segelke, D., Guillaume, F., Bouet, S., Baur, A., Vasilescu, A., Genestout, L., Thomas, A., Allais-Bonnet, A., Rocha, D., Colle, M.A., Klopp, C., Esquerré, D., Wurmser, C., Flisikowski, K., Schwarzenbacher, H., Burgstaller, J., Brügmann, M., Dietschi, E., Rudolph, N., Freick, M., Barbey, S., Fayolle, G., Danchin-Burge, C., Schibler, L., Bed'Hom, B., Hayes, B.J., Daetwyler, H.D., Fries, R., Boichard, D., Pin, D., Drögemüller, C., Capitan, A. :|
|Rapid discovery of de novo deleterious mutations in cattle enhances the value of livestock as model species. Sci Rep 7:11466, 2017. Pubmed reference: 28904385. DOI: 10.1038/s41598-017-11523-3.|
|2015||Dorshorst, B., Henegar, C., Liao, X., Sällman Almén, M., Rubin, C.J., Ito, S., Wakamatsu, K., Stothard, P., Van Doormaal, B., Plastow, G., Barsh, G.S., Andersson, L. :|
|Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene. PLoS One 10:e0128969, 2015. Pubmed reference: 26042826. DOI: 10.1371/journal.pone.0128969.|
|2014||Capitan, A., Michot, P., Guillaume, F., Grohs, C., Djari, A., Fritz, S., Barbey, S., Otz, P., Bourneuf, E., Rocha, D., Esquerré, D., Gallard, Y., Klopp, C., Boichard, D. :|
|Rapid discovery of mutations responsible for sporadic dominant genetic defects in livestock using genome sequence data: Enhancing the value of farm animals as model species. 10th World Congr. Genet. Appl. Livest. Sci., Aug. 21 :presentation 182, 2014.|
|Lawlor, T.J., VanRaden, P.M., Null, D., Levisee, J., Dorhorst, B. :|
|Using haplotypes to unravel the inheritance of Holstein coat color. Proc. 10th World Congr. Genet. Appl. Livest. Prod., Vancouver, BC, Canada, Aug. 17–22 :Comm. 289, 2014.|
|2010||Dreger, DL., Schmutz, SM. :|
|The variant red coat colour phenotype of Holstein cattle maps to BTA27. Anim Genet 41:109-12, 2010. Pubmed reference: 19793268. DOI: 10.1111/j.1365-2052.2009.01969.x.|
|2006||Leduc, M. :|
|The various mechanisms of red colour transmission in the Holstein breed. Holstein Journal 69:17-19, 2006.|
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