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"TYRP1 is Associated With Dun Coat Colour in Dexter Cattle

or How Now Brown Cow?"
by T.G. Berryere, S.M Schmutz, R.J. Schimpf, C.M. Cowan and J. Potter,

Animal Genetics, Volume 34, Issue 3, June 2003, pages 169-175.

 

NOTES:

1) Terms with hyperlinks are explained in the Glossary at the foot of the page. Click on the term to go to its explanation. Click the "Back" button at the top left had corner of the screen to return to your place in the text.

2) Also at the bottom of this page are links to comments on this article and to other online material about Dexters and the genetics of coat colour.

 

~~ Start of Article Summary ~~

 

Introduction

 

Dilution of the predominant coat colour in cattle can occur in a number of different ways. [If a cow's primary genes for colour lead to the production of eumelanin pigment, then coat colour will be black. If the genes lead to the production of phaeomelanin, then coat colour will be red. Both of these pigments may be "diluted" due to other genes, resulting in a different colour.] Cattle coat colours such as dun, white, cream, yellow, grey, brown and pale red, are possible results of such dilution. It can be difficult to distinguish visually these colours clearly, and the same name is sometimes used to describe different colours in different breeds.

 

Dun is a pale coat colour over the entire body. It is a term that has been used to describe a range of golden brown to dark brown shades in Dexters. The Dexter dun is considered to be inherited as an "autosomal recessive" [that is, a cow must have two copies of the dun gene to actually be dun].

 

The research project focussed on the "tyrosinase related protein 1" (TYRP1) gene which is one of three proteins that control the dilution of coat colour, affecting coat colours associated with a dilution of eumelanin (black) (though an effect on phaeomelanin - red pigment - cannot be ruled out). Previous research has been done on the TYRP1 gene in mice, dogs and people. Mutations of TYRP1 in mice and dogs have resulted in different shades of brown.

 

"In this study, we mapped TYRP1 using embryo transfer cattle families. We [also] attempted to study the possible effects of TYRP1 mutations on dilution of phaeomelanin using a crossbred Charolais half-sib family and a Simmental full-sib family. However, we concentrated on studying the dilution effects on eumelanin, particularly by studying a family of dun Dexter cattle."

 

Materials and Methods

 

Seventeen full-sib families of 2-17 calves were generated from an embryo transfer process. The breeds were Angus, Belgian Blue, Charolais, Hereford, Limousin and Simmental, all breeds containing a range of different colours. Three additional families were also studied. A crossbred Charolais/Red Angus bull was bred to 17 Simmental/Hereford crossbred red dams - 10 of the resulting calves were red and 5 were diluted to tan. Furthermore, Galloway calves from dun Belted Galloway bull and black Belted Galloway dams were used to test linkage of TYRP1 gene and the dun coat colour in this breed.

 

"A black Dexter cow, heterozygous for dun [carries only one dun allele], produced five calves from three different sires who were dun or heterozygous for dun. Samples from this family were used to study the dilution of eumelanin. The DNA from over 100 cattle of 19 breeds were also obtained to screen for a TYRP1 mutation." [Samples were obtained from other Dexters of different colours as well.]

 

[There follows four paragraphs of very technical descriptions of genetic and chemical methods, e.g. "The exon 7 purposeful mismatch primer (Ex7MM) and the exon 7 reverse primer (Ex7) amplified a 141-bp product in most animals using the above PCR protocol. The resulting PCR product was cut with HaeIII and run on a 5% agarose gel."]

 

[The "Results" sections are also very technical, but include the following statements about the Dexters studied:]

 

"All 25 dun Dexter cattle were homozygous for tyrosine at amino acid 434 (codon TAT), regardless of the shade of dun that ranged from a pale golden to dark brown." Of 58 Dexter cattle of black coat colour, 42 were "heterozygous for this SNP" [single nucleotide polymorphism] and 16 were "homozygous for histidine (codon CAT) at this site". One of the 13 red Dexter cattle was "" homozygous for tyrosine and was 'E+/E+' at MC1R. All 25 of the dun Dexters genotyped had at least one 'ED' allele, indicating they produced eumelanin." [MC1R is the gene on cattle chromosome 18 that determines black or red. TYRP1 is a gene on cattle chromosome 8.]

 

[In her Paper on this research to the Second World Dexter Congress in 2002, Carol Davidson summed up the significance of this paragraph, saying that a mutation in the TYRP1 gene "has caused an amino acid, histidine, to be replaced by tyrosine in dun Dexters".]

 

"The complete MC1R sequence of three dun Dexters of various shades revealed no new polymorphisms [types of gene interactions]. The shade of dun was not correlated to the presence or absence of an 'E+' allele. In addition to 90 Dexter cattle, we examined 121 cattle of other breeds and did not find this TYRP1 mutation in any of them. We included cattle of a variety of coat colours for each breed in which such variation occurred."

 

Discussion

 

It was discovered that the TYRP1 gene is located on bovine chromosome 8.

 

The TYRP1 gene detected in the two Simmental parents, a dun Belted Galloway sire and a Charolais/Red Angus sire did not influence their diluted coat colours which are inherited in a different way. The TYRP1 gene is also not responsible for the taupe brown colour in the Braunvieh or Swiss Brown.

 

"The amino acid change detected in all 25 dun Dexter cattle we examined was a tyrosine which is polar and neutral, replacing a histidine which is basic. This type of non-conservative amino acid change is consistent with a functional mutation."

 

Research on mice and dogs has shown that mutations in TYRP1 alter the shade of eumelanin pigment to various shades of brown. These mutations "occur in several different exons of TYRP1, but none affect amino acid 434 as did the dun Dexter mutation. Shades of eumelanin or brown pigment produced by TYRP1 mutations in mice and dogs vary widely but these colours are similar to the shades of coat colour in dun Dexter cattle." The authors suggest that this TYRP1 cattle allele be termed 'b', consistent with the terms used for mice.

 

Research on dogs also showed that there were interactions between the two genes, MC1R and TYRP1, so that a dog with "an 'e/e' genotype and homozygous for a premature stop codon in MC1R had phaeomelanin rather than eumelanin hair pigmentation and therefore their coat colour was not brown. However, the colour of their nose leather and pads was brown rather than black when they were homozygous for TYRP1 mutations. The red Dexter heifer that was homozygous for tyrosine at position 434 provides evidence that MC1R and TYRP1 also interact in cattle. This heifer produced phaeomelanin which is not affected by TYRP1. All of the dun Dexter cattle had at least one copy of the 'ED' allele at MC1R and therefore produced eumelanin constitutively. A dun Dexter animal must have the genotype 'ED/_, b/b'."

 

"Thus far, the 'b' allele of TYRP1 has been found only in Dexter cattle. None of the other 118 cattle of 18 other breeds examined had this allele. Dexter cattle were developed in Ireland and were often noted for their short stature but not for any specific coat colour. It may be that this mutation arose in the Dexter breed and therefore is relatively recent in evolutionary time."

 

[In her Paper to the Second World Dexter Congress in 2002, Carol Davidson closes by referring to John Potter as saying that this is the discovery of the first brown mutation ever found in cattle, and one that as of this time proves to be unique to Dexters.]

 

Acknowledgements

 

Included: "We are also very grateful to Anthony Bauer for arranging and coordinating the collection of Dexter samples and to the Dexter breeders across Canada and the United States who furnished hair, blood, and semen samples for this study."   

~~ End of Article Summary ~~

 

GLOSSARY

 

allele - half of a gene, which can vary. A gene consists of two alleles, one from the father, one from the mother.

amino acid - an organic compound, an essential component of a protein.

autosomal recessive - autosomal recessive traits are those in which two copies of the same allele are required for the trait to be expressed (shown in the phenotype of the animal). By contrast, autosomal dominant traits are those in which a single copy of an allele is enough for the trait to be expressed.

chromosome - part of a cell, contains the genes; for a diagram, see www.phoenix5.org/glossary/chromosomes.html.

codon - a sequence of three adjacent nucleotides on a DNA molecule that specifies the insertion of an amino acid in a specific structural position during protein synthesis. The four important components of DNA are Thymine, Adenine, Guanine, and Cytosine (TAGC) - these occur in a variety of sequences. When put into groups of three, each group is called a codon, each codon codes for a specific amino acid, e.g. AAA codes for a type of amino acid called phenylalanine; there is a unique codon for each of the 20 amino acids (taken from www.angelfire.com/ms/perring/genetics.html). 

dilution - change to the coat colour of an animal due to the dilution - caused by one gene (TYRP1 in this case) - of the basic pigmentation -determined by another gene (MC1R in this case).

eumelanin - a pigment causing cattle coat to be black.

exon - a region of a gene that is present in the final functional transcript (mRNA) from that gene. Exons are interspersed with introns; together the exons constitute the mRNA (messenger RNA) and are translated into protein; an exon is a sequence of a gene's DNA that transcribes into protein structures (comes from shortening of "expressed on"); for a diagram, see http://ghs.gresham.k12.or.us/science/ps/sci/ibbio/chem/nucleic/chpt15/intron.htm.

gene - a hereditary unit located on a chromosome; genes are pieces of DNA, and most genes contain the information for making a specific protein; for a diagram, see www.phoenix5.org/glossary/gene.html.

genotype - the genes carried by an animal (e.g., black/red); to be contrasted with the phenotype, the appearance of an animal (e.g., a black/red genotype in Dexters has the phenotype of red).

heterozygous - a gene in which the two alleles are different (e.g., black/red).

histidine - an amino acid.

homozygous - a gene in which the two alleles are the same (e.g., dun/dun).

MC1R - a gene, "melancortin receptor 1", located on cattle chromosome 18, which determines the basic coat colour of cattle by determining the production of either eumelanin or phaeomelanin; but its effects can be modified by the TYRP1 gene.   

mutation - a heritable alteration of a gene; a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the amino acid sequence of the protein encoded by the gene. For comments on causes of mutations, see http://gslc.genetics.utah.edu/units/disorders/sloozeworm/mutationbg.cfm.

phaeomelanin - a pigment causing cattle coat to be red.

phenotype - the appearance of an animal (e.g., red coat colour); to be contrasted with the genotype, the genes carried by an animal (e.g., black/red).

premature stop - part of a gene (the sequence of Thymine, Adenine, Guanine, and Cytosine) altered by a mutation which interrupts the normal biochemical processes governed by the gene.

protein - a complex nitrogenous organic compound that contains amino acids as its basic structural units.

tyrosinase - an enzyme that catalyses the production of melanin from tyrosine. Tyrosine is a non-essential amino acid, a precursor of adrenaline, thryoxine and melanin.

TYRP1 - a gene, "tyrosinase related protein 1", located on cattle chromosome 8; one of three proteins that control the dilution of coat colour produced by the MC1R gene.

 

FURTHER COMMENTS AND INFORMATION ON THE GENETICS OF COAT COLOUR IN DEXTERS

 

Comments by Sheila Schmutz [Sheila confirms the findings of this Article]

 

Comments by Carol Davidson [from a discussion board posting]

 

John Potter's comments

   "Color Genetics and the Registration of Dexter Cattle" (ADCA website) www.dextercattle.org/colorgenetics.htm

    "DNA Testing for Dexter Cattle: An Update" (John Potter, ADCA Genetics Committee, 1/1/2004)

          www.blockcreekranch.com/ref/DNA_Testing1.htm
 

Gabriella Nanci's article on "Dexter Colors" http://bellefourchedexters.tripod.com/Articles/dexter_colors.htm
 

An Article relevant to the dun gene in Dexters - "Grade One - and the Colour Dun"

 

A website of a Dun Dexter Herd, with further comments on the dun colour - www.dundexters.co.nz

 

 

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