OMIA 001529-9913 : Coat colour, dominant red in Bos taurus

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).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COPA coatomer protein complex subunit alpha Bos taurus 3 NC_037330.1 (9350590..9394691) COPA 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 Year Published PubMed ID(s) Acknowledgements
Holstein Dominant red COPA DR^DR missense UMD3.1 3 g.9479761C>T c.478C>T p.R160C 2017 28904385 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
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., 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.

Edit History


  • Created by Frank Nicholas on 04 Nov 2010
  • Changed by Frank Nicholas on 22 Jan 2015
  • Changed by Frank Nicholas on 23 Jan 2015
  • Changed by Frank Nicholas on 24 Mar 2015
  • Changed by Frank Nicholas on 11 Jun 2015
  • Changed by Frank Nicholas on 18 Sep 2017
  • Changed by Frank Nicholas on 19 Sep 2017