Molecular Biology Reports

, Volume 38, Issue 5, pp 2927–2932 | Cite as

Two novel SNPs of the ABCG2 gene and its associations with milk traits in Chinese Holsteins

  • Wangping Yue
  • Xingtang Fang
  • Chunlei Zhang
  • Yonghong Pang
  • Haixia Xu
  • Chuanwen Gu
  • Ruying Shao
  • Chuzhao Lei
  • Hong ChenEmail author


The ATP-binding cassette transporter ABCG2 (also known as breast cancer resistance protein, BCRP) belongs to the ATP-binding cassette (ABC) family of transmembrane drug transporters, playing a crucial role in the protection of various cells and tissues against xenotoxins and/or endotoxins. Recently, several studies have proposed it as the potential gene underlying the QTL on bovine chromosome 6. Hence, in this study, the PCR-SSCP method was applied to detect two polymorphisms (A → C and A → G) in the target sequence coding nucleotide-binding domain (NBD) region of ABCG2 and evaluate its associations with milk production traits and mastitis-related traits among Chinese Holsteins. In the analyzed population, the allelic frequencies for the A and B alleles were 0.5990 and 0.4010, respectively and the genotypic frequencies were in Hardy–Weinberg disequilibrium (P < 0.01). Moreover, significant statistical relationships between the polymorphisms of ABCG2 gene and following traits, including milk yields, milk protein percentage and somatic cell scores (SCS), were found (P < 0.05). When compared with AA genotype, BB genotype was associated with higher milk yields during 1st and 2nd lactations, as well as lower milk protein percentage and SCS. Thus, BB genotype is suggested to be a molecular marker for superior milk performance.


ABCG2 Milk traits Mastitis Polymorphisms Chinese Holsteins 



This study was supported by the National 863 Program of China (No. 2006AA10Z197, 2008AA101010), National Natural Science Foundation of China (No.30771544, 30972080), National Key Technology R&D Program (No. 2006BAD01A10-5), Keystone Project of transfergene in China(2009ZX08009-157B,2008ZX08007-002), “13115” Sci-Tech Innovation Program of Shaanxi Province (2008ZDKG-11), Program of National Beef Cattle Industrial Technology System; Natural science fund for colleges and universities in Jiangsu Province (09KJD180002).


  1. 1.
    Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113PubMedCrossRefGoogle Scholar
  2. 2.
    Childs S, Ling V (1994) The MDR superfamily of genes and its biological implications. Important Adv Oncol 21–36Google Scholar
  3. 3.
    Dean M, Allikmets R (1995) Evolution of ATP-binding cassette transporter genes. Curr Opin Genet Dev 5:779–785PubMedCrossRefGoogle Scholar
  4. 4.
    Klein I, Sarkadi B, Varadi A (1999) An inventory of the human ABC proteins. Biochim Biophys Acta 1461:237–262PubMedCrossRefGoogle Scholar
  5. 5.
    Stefkova J, Poledne R, Hubacek JA (2004) ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res 53:235–243PubMedGoogle Scholar
  6. 6.
    Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Hayden MR (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22:336–345PubMedCrossRefGoogle Scholar
  7. 7.
    Albrecht C, Baynes K, Sardini A, Schepelmann S, Eden ER, Davies SW, Higgins CF, Feher MD, Owen JS, Soutar AK (2004) Two novel missense mutations in ABCA1 result in altered trafficking and cause severe autosomal recessive HDL deficiency. Biochim Biophys Acta 1689:47–57PubMedGoogle Scholar
  8. 8.
    Albrecht G, Simon-Vermot I, Elliott II, Higgins CF, Johnston DG, Valabhji J (2004) Lencocyte gene expression is associated with fasting glucose concentration in normoglycemic men. Metabolism 53:15–21CrossRefGoogle Scholar
  9. 9.
    Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290:1771–1775PubMedCrossRefGoogle Scholar
  10. 10.
    Jonker JW, Merino G, Musters S, van Herwaarden AE, Bolscher E, Wagenaar E, Mesman E, Dale TC, Schinkel AH (2005) The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med 11:127–129PubMedCrossRefGoogle Scholar
  11. 11.
    Wu HJ, Luo J, Wu N, Matand K, Zhang LJ, Han XF, Yang BJ (2008) Cloning, sequence and functional analysis of goat ATP-binding cassette transporter G2 (ABCG2). Mol Biotechnol 39:21–27PubMedCrossRefGoogle Scholar
  12. 12.
    van Herwaarden AE, Wagenaar E, Merino G, Jonker JW, Rosing H, Beijnen JH, Schinkel AH (2007) Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. Mol Cell Biol 27:1247–1253PubMedCrossRefGoogle Scholar
  13. 13.
    Shukla S, Wu CP, Nandigama K, Ambudkar SV (2007) The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2. Mol Cancer Ther 6:3279–3286PubMedCrossRefGoogle Scholar
  14. 14.
    Mizuarai S, Aozasa N, Kotani H (2004) Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. Int J Cancer 109:238–246PubMedCrossRefGoogle Scholar
  15. 15.
    Sparreboom A, Gelderblom H, Marsh S, Ahluwalia R, Obach R, Principe P, Twelves C, Verweij J, McLeod HL (2004) Diflomotecan pharmacokinetic in relation to ABCG2 421C > A genotype. Clin Pharmacol Ther 76:38–44PubMedCrossRefGoogle Scholar
  16. 16.
    Yamasaki Y, Ieiri I, Kusuhara H, Sasaki T, Kimura M, Tabuchi H, Ando Y, Irie S, Ware J, Nakai Y, Higuchi S, Sugiyama Y (2008) Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans. Mol Ther (Jan 2 Epub ahead of print)Google Scholar
  17. 17.
    Cohen-Zinder M, Seroussi E, Larkin DM, Loor JJ, Everts-van der Wind A, Lee JH, Drackley JK, Band MR, Hernandez AG, Shani M, Lewin HA, Weller JI, Ron M (2005) Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle. Genome Res 15:936–944PubMedCrossRefGoogle Scholar
  18. 18.
    Schnabel RD, Kim JJ, Ashwell MS, Sonstegard TS, Van Tassell CP, Connor EE, Taylor JF (2005) Fine-mapping milk production quantitative trait loci on BTA6: analysis of the bovine osteopontin gene. Proc Natl Acad Sci USA 102:6896–6901PubMedCrossRefGoogle Scholar
  19. 19.
    Olsen HG, Nilsen H, Hayes B, Berg PR, Svendsen M, Lien S, Meuwissen T (2007) Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle. BMC Genet 8:32PubMedCrossRefGoogle Scholar
  20. 20.
    Mullenbach R, Lagoda PJ, Welter C (1989) An efficient salt-chloroform extraction of DNA from blood and tissue. Trends Genet 5:391PubMedGoogle Scholar
  21. 21.
    Qiu H (1995) Cattle production. Chinese Agriculture Press, Beijing, ChinaGoogle Scholar
  22. 22.
    Zhang CL, Wang Y, Chen H, Lan XY, Lei CZ (2007) Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining. Anal Biochem 365:286–287PubMedCrossRefGoogle Scholar
  23. 23.
    Mead R, Curnow RN (1985) Statistical methods in agriculture and experimental biology. Chapman and Hall, London, UKGoogle Scholar
  24. 24.
    Nei M, Roychoudhurg AK (1974) Sampling variance of heterozygosity and genetic distance. Genetics 76:379–390PubMedGoogle Scholar
  25. 25.
    Nei M, Li WH (1979) Mathematic model for studying genetic variation in terms of restriction endonucleases. PNAS USA 76:5269–5273PubMedCrossRefGoogle Scholar
  26. 26.
    Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms Am J Hum Genet 32:314–331PubMedGoogle Scholar
  27. 27.
    Litman T, Brangi M, Hudson E, Fetch P, Abati A, Ross DD, Miyake K, Resau JH, Bates SE (2000) The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113:2011–2021PubMedGoogle Scholar
  28. 28.
    Schmitz G, Langmann T, Heimer D (2001) Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res 49:1513–1520Google Scholar
  29. 29.
    LeHir H, Nott A, Moore M (2003) How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 28:215–220CrossRefGoogle Scholar
  30. 30.
    Greenwood TA, Kelsoe JR (2003) Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics 82:511–520PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Wangping Yue
    • 1
  • Xingtang Fang
    • 1
  • Chunlei Zhang
    • 1
  • Yonghong Pang
    • 2
  • Haixia Xu
    • 1
  • Chuanwen Gu
    • 1
  • Ruying Shao
    • 1
  • Chuzhao Lei
    • 2
  • Hong Chen
    • 1
    Email author
  1. 1.Institute of Cellular and Molecular Biology, College of Life ScienceXuzhou Normal UniversityXuzhouPeople’s Republic of China
  2. 2.Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and TechnologyNorthwest A&F UniversityYanglingChina

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