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A large insertion in intron 2 of the TYRP1 gene associated with American Palomino phenotype in American mink

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Abstract

A number of American mink phenotypes display a range of brownish colours. One of these phenotypes, namely American Palomino (b P b P ) (AP) has been found to be associated with the tyrosinase-related protein 1 (TYRP1) gene by genotyping microsatellite markers in one sire family. Trials for amplifying the genomic DNA and cDNA at the beginning of intron 2 of AP TYRP1 revealed the presence of a large insertion of approximately eight kb. The insertion most likely disrupts different elements necessary for the splicing of intron 2 of the TYRP1 gene. In AP RNAseq data indicate, however, the presence of the wild-type (wt) transcript at very low levels and Western blot reveals three products when using an antibody raised against middle part of the TYRP1 protein. One individual from another brown mink phenotype—commercially named Dawn—was also investigated at the molecular level by long-range PCR and the same size insertion appears to be present. By this we suggest that certain modifiers of TYRP1 would induce different brown colour degradation, which results in at least two different phases of brown.

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References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410

    Article  CAS  PubMed  Google Scholar 

  • Anistoroaei R, Menzorov A, Serov O, Farid A, Christensen K (2007) The first linkage map of the American mink (Mustela vison). Anim Genet 38:384–388

    Article  CAS  PubMed  Google Scholar 

  • Anistoroaei R, Fredholm M, Christensen K, Leeb T (2008) Albinism in the American mink (Neovison vison) is associated with a tyrosinase nonsense mutation. Anim Genet 39:645–648

    Article  CAS  PubMed  Google Scholar 

  • Anistoroaei R, ten Hallers B, Nefedov M, Christensen K, de Jong P (2011) Construction of an American mink Bacterial Artificial Chromosome (BAC) library and sequencing candidate genes important for the fur industry. BMC Genom 12:354

    Article  CAS  Google Scholar 

  • Anistoroaei R, Krogh AK, Christensen K (2012) A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Chediak-Higashi syndrome in American mink. Anim Genet 44(2):178–183

    Article  PubMed  Google Scholar 

  • Benkel BF, Rouvinen-Watt K, Farid H, Anistoroaei R (2009) Molecular characterization of the Himalayan mink. Mamm Genome 20(4):256–259

    Article  CAS  PubMed  Google Scholar 

  • Bennett DC, Huszar D, Laipis PJ, Jaenisch R, Jackson IJ (1990) Phenotypic rescue of mutant brown melanocytes by a retrovirus carrying a wild-type tyrosinase-related protein gene. Development 110:471–475

    CAS  PubMed  Google Scholar 

  • Berryere TG, Schmutz SM, Schimpf RJ, Cowan CM, Potter J (2003) TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow? Anim Genet 34:169–175

    Article  CAS  PubMed  Google Scholar 

  • Cirera S, Markakis MN, Christensen K, Anistoroaei R (2013) New insights into the melanophilin (MLPH) gene controlling coat colour phenotypes in American mink. Gene 527(1):48–54

    Article  CAS  PubMed  Google Scholar 

  • Galante PAF, Sakabe NJ, Kirschbaum-Slager N, de Souza SJ (2004) Detection and evaluation of intron retention events in the human transcriptome. RNA 10:757–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graphodatsky A, Yang F, Serdukova N, Perelman P, Zhdanova N, Ferguson-Smith M (2000) Dog chromosome-specific paints reveal evolutionary inter- and intrachromosomal rearrangements in the American mink and human. Cytogenet Cell Genet 90:275–278

    Article  CAS  PubMed  Google Scholar 

  • Gratten J, Beraldi D, Lowder BV, McRae AF, Visscher PM, Pemberton JM, Slate J (2007) Compelling evidence that a single nucleotide substitution in TYRP1 is responsible for coat-colour polymorphism in a free-living population of Soay sheep. Proc Biol Sci 274:619–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halaban R, Moellmann G (1990) Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity. Proc Natl Acad Sci USA 87:4809–4813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hameister H, Klett C, Bruch J, Dixkens C, Christensen K (1997) Zoo-FISH analysis: the American mink (Mustela vison) closely resembles the cat karyotype. Chromosome Res 5(1):5–11

    Article  CAS  PubMed  Google Scholar 

  • Hearing VJ (1999) Biochemical control of melanogenesis and melanosomal organization. J Invest Dermatol Symp Proc 4:24–28

    Article  CAS  Google Scholar 

  • Hearing VJ (2005) Biogenesis of pigment granules: a sensitive way to regulate melanocyte function. J Dermatol Sci 37:3–14

    Article  CAS  PubMed  Google Scholar 

  • Hearing VJ, Tsukamoto K (1991) Enzymatic control of pigmentation in mammals. FASEB J 5:2902–2909

    CAS  PubMed  Google Scholar 

  • Jackson IJ (1988) A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse. Proc Natl Acad Sci USA 85:4392–4396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenny EE, Timpson NJ, Sikora M, Yee M-C, Moreno-Estrada A, Eng C, Huntsman S, Burchard EG, Stoneking M, Bustamante CD, Myles S (2012) Melanesian blond hair is caused by an amino acid change in TYRP1. Science 336(6081):554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King RC (1951) Genetics of mink. International Publishers Co, Duluth

    Google Scholar 

  • Kobayashi T, Hearing VJ (2007) Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo. J Cell Sci. 120(Pt 24):4261–4268

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Urabe K, Winder A, Jimenez-Cervantes C, Imokawa G, Brewington T, Solano F, Garcia-Borron JC, Hearing VJ (1994) Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J 13:5818–5825

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lamoreux LM, Delmas V, Larue L, Bennett DC (2010) The colors of mice. A model genetic network. Wiley, Hoboken. ISBN 978-1-4051-7954-6

    Book  Google Scholar 

  • Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Meth 9(4):357–359

    Article  CAS  Google Scholar 

  • Luo R, Liu B, Xie Y, Li Z, Huang W, Yuan J, He G, Chen Y, Pan Q, Liu Y, Tang J, Wu G, Zhang H, Shi Y, Liu Y, Yu C, Wang B, Lu Y, Han C, Cheung DW, Yiu SM, Peng S, Xiaoqian Z, Liu G, Liao X, Li Y, Yang H, Wang J, Lam TW, Wang J (2012) SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler. GigaScience 1:18

    Article  PubMed  PubMed Central  Google Scholar 

  • Lyons LA, Foe IT, Rah HC, Grahn RA (2005) Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. Mamm Genome 16:356–366

    Article  CAS  PubMed  Google Scholar 

  • Mohanty TR, Seo KS, Park KM, Choi TJ, Choe HS, Baik DH, Hwang IH (2008) Molecular variation in pigmentation genes contributing to coat colour in native Korean Hanwoo cattle. Anim Genet 39(5):550–553

    Article  CAS  PubMed  Google Scholar 

  • Nadeau NJ, Mundy NI, Gourichon D, Minvielle F (2007) Association of a single-nucleotide substitution in TYRP1 with roux in Japanese quail (Coturnix japonica). Anim Genet 38:609–613

    Article  CAS  PubMed  Google Scholar 

  • Nes NN, Einarsson EJ, Lohi O (1988) Beautiful fur animals—and their colour genetics. Scientifur, Hilleroed

    Google Scholar 

  • Nonneman D, Shibuya H, Johnson GS (1996) A BstUI PCR/RFLP in the bovine tyrosinase-related protein-1 (TYRP1) gene. Anim Genet 27(3):218–219

    Article  PubMed  Google Scholar 

  • Ozeki H, Ito S, Wakamatsu K, Hirobe T (1995) Chemical characterization of hair melanins in various coat-color mutants of mice. J Invest Dermatol 105:361–366

    Article  CAS  PubMed  Google Scholar 

  • Raadsma HW, Jonas E, Fleet MR, Fullard K, Gongora J, Cavanagh CR, Tammen I, Thomson PC (2013) QTL and association analysis for skin and fibre pigmentation in sheep provides evidence of a major causative mutation and epistatic effects. Anim Genet 44(5):547–559

    Article  CAS  PubMed  Google Scholar 

  • Ren J, Mao H, Zhang Z, Xiao S, Ding N, Huang L (2011) A 6-bp deletion in the TYRP1 gene causes the brown colouration phenotype in Chinese indigenous pigs. Heredity 106:862–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rieder S, Taourit S, Mariat D, Langlois B, Guérin G (2001) Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mamm Genome 12(6):450–455

    Article  CAS  PubMed  Google Scholar 

  • Schmidt-Küntzel A, Eizirik E, O’Brien SJ, Menotti-Raymond M (2005) Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. J Hered 96:289–301

    Article  PubMed  Google Scholar 

  • Schmutz SM, Berryere TG, Goldfinch AD (2002) TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mamm Genome 13(7):380–387

    Article  CAS  PubMed  Google Scholar 

  • Shackelford RM (1980) Domestic Production of Mink and Foxes. In: Proceedings of the 29th annual National Breeders’ Roundtable. http://www.poultryscience.org/docs/pba/1952-2003/1980/1980%20Shackelford.pdf

  • Sturm RA, O’Sullivan BJ, Box NF, Smith AG, Smit SE, Puttick ER, Parsons PG, Dunn IS (1995) Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family. Genomics 29(1):24–34

    Article  CAS  PubMed  Google Scholar 

  • Toyofuku K, Wada I, Valencia JC, Kushimoto T, Ferrans VJ, Hearing VJ (2001) Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. FASEB J 15(12):2149–2161

    Article  CAS  PubMed  Google Scholar 

  • Walsh PS, Metzger DA, Higuchi R (1991) Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques 10:506–513

    CAS  PubMed  Google Scholar 

  • Wang N, Hebert DN (2006) Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Res 19:3–18

    Article  PubMed  Google Scholar 

  • Zdarsky E, Favor J, Jackson IJ (1990) The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type. Genetics 126(2):443–449

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zerbino DR, Birney E (2008) velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18:821–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Xin D, Wang P, Zhou L, Hu L, Kong X, Hurst LD (2009) Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay. BMC Biol 7:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported from private funding. We are thankful to Tina B. Neergaard Mahler and Minna Jakobsen for technical assistance. We acknowledge Boye Pedersen who is in charge of the KU mink farm. We also acknowledge Jesper Clausen for providing some of the pictures of the mink.

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Correspondence to Razvan Anistoroaei.

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The authors declare not having any conflict of interest. The authors are investigation scientists and although they work with a politically controversial fur animal species, herein they are only supporters of the science. Their political view might therefore differ from the line of research they are engaged in.

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335_2016_9620_MOESM1_ESM.tif

Brown spectrum in American mink. American Palomino, Dawn and wild type are indicated. Photograph: Jesper Clausen (TIFF 2174 kb)

335_2016_9620_MOESM2_ESM.tif

Mink phenotypes homozygous for the TYRP1 mutation: (A) American Palomino b P b P and (B) Dawn besides a wild type mink (C) (TIFF 883 kb)

335_2016_9620_MOESM3_ESM.tif

Pedigrees segregating informatively for American Palomino phenotype in American mink. Circles represent females, squares represent males, rombes unrecorded sex. Solid symbols represent American Palomino homozygotes (bb) and clear symbols represent wild type (homo- or heterozygous; BB or Bb) individuals (TIFF 683 kb)

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Cirera, S., Markakis, M.N., Kristiansen, T. et al. A large insertion in intron 2 of the TYRP1 gene associated with American Palomino phenotype in American mink. Mamm Genome 27, 135–143 (2016). https://doi.org/10.1007/s00335-016-9620-4

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