Skip to main content

Advertisement

SpringerLink
Log in

Mannose-binding lectin 1 haplotypes influence serum MBL-A concentration, complement activity, and milk production traits in Chinese Holstein cattle

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Mannose-binding lectin (MBL) is a member of the collectin protein family that binds a broad range of microorganisms and activates the lectin-complement pathway of innate immunity. MBL deficiency is associated with an increased risk for various infections and arises from five polymorphisms in the promoter and first exon of the MBL gene in humans. In this study, three novel single-nucleotide polymorphisms (SNPs) in the promoter region and two previously reported SNPs in exon 2 of the MBL1 gene were detected using PCR single-strand conformation polymorphism, restriction fragment length polymorphism, and DNA sequencing in 537 cattle from three Chinese breeds. Analysis of the genotypes and haplotypes was used to investigate the polymorphisms and their possible implications, especially their association with serum MBL-A levels, complement activity (CH50 and ACH50), and milk production traits was investigated. The g.2651G>A SNP in exon 2 affected the serum MBL-A concentrations and the serum CH50 values, whereas the g.−1330G>A SNP significantly affected CH50 and the somatic cell scores (SCSs). Statistical analysis revealed that cows with the ATGGC/ACAAC combined genotype and those with the AAGGT/ACGGT combined genotype exhibited the lowest and highest SCSs, respectively. Serum antibacterial activities were also conducted to verify the effect of the SNPs on resistance to mastitis pathogens. Results of real-time PCR showed that the liver of cows with clinical mastitis exhibited a higher MBL1 expression compared with healthy ones (P < 0.05). Findings of this study indicate that the MBL1 gene possibly contributes to bacterial infection resistance and can be used as a molecular marker of milk production traits to control mastitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Agah A, Montalto MC, Young K, Stahl GL (2001) Isolation, cloning and functional characterization of porcine mannose-binding lectin. Immunology 102:338–343

    Article  PubMed  CAS  Google Scholar 

  • Ali AKA, Shook GE (1980) An optimum transformation for somatic cell concentration in milk. J Dairy Sci 63:487–490

    Article  Google Scholar 

  • Botto M, Fong KY, So AK, Koch C, Walport MJ (1990) Molecular basis of polymorphisms of human complement component C3. J Exp Med 172:1011–1117

    Article  PubMed  CAS  Google Scholar 

  • Brigati C, Kurtz S, Balderes D, Vidali G, Shore D (1993) An essential yeast gene encoding a TTAGGG repeat-binding protein. Mol Cell Biol 13:1306–1314

    PubMed  CAS  Google Scholar 

  • Brönnestam R (1973) Studies of the C3 polymorphism. Relationship between C3 phenotypes and rheumatoid arthritis. Hum Hered 23:206–213

    Article  PubMed  Google Scholar 

  • Capparelli R, Parlato M, Amoroso MG, Roperto S, Marabelli R, Roperto F, Iannelli D (2008) Mannose-binding lectin haplotypes influence Brucella abortus infection in the water buffalo (Bubalus bubalis). Immunogenetics 60:157–165

    Article  PubMed  CAS  Google Scholar 

  • Dailey L, Roberts SB, Heintz N (1988) Purification of the human histone H4 gene-specific transcription factors H4TF-1 and H4TF-2. Gene Dev 2:1700–1712

    Article  PubMed  CAS  Google Scholar 

  • Duncan DB (1955) Multiple range and multiple F tests. Biometrics 11:1–42

    Article  Google Scholar 

  • Eisen DP, Minchinton RM (2003) Impact of mannose-binding lectin on susceptibility to infectious diseases. J Infect Dis 37:1496–1505

    Article  CAS  Google Scholar 

  • Fallin D, Cohen A, Essioux L, Chumakov I, Blumenfeld M, Cohen D, Schork NJ (2001) Genetic analysis of case/control data using estimated haplotype frequencies: application to APOE locus variation and Alzheimer’s disease. Genome Res 11:143–151

    Article  PubMed  CAS  Google Scholar 

  • Fonseca I, Silva PV, Lange CC, Guimarães MFM, Weller MMDCA, Sousa KRS, Lopes PS, Guimarães JD, Guimarães SEF (2009) Expression profile of genes associated with mastitis in dairy cattle. Genet Mol Biol 32:776–781

    Article  PubMed  CAS  Google Scholar 

  • Holmskov U, Thiel S, Jensenius JC (2003) Collectins and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol 21:547–578

    Article  PubMed  CAS  Google Scholar 

  • Ito T, Nomura S, Okada M, Katsumata Y, Kikkawa F, Rogi T, Tsujimoto M, Mizutani S (2002) AP-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene. Biochem Biophys Res Commun 290:1048–1053

    Article  PubMed  CAS  Google Scholar 

  • Jack DL, Read RC, Tenner AJ, Frosch M, Turner MW, Klein NJ (2001) Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B. J Infect Dis 184:1152–1162

    Article  PubMed  CAS  Google Scholar 

  • Juul-Madsen HR, Krogh-Meibom T, Henryon M, Palaniyar N, Heegaard PMH, Prup S, Willis AC, Tornøe I, Ingvartsen KL, Hansen S, Holmskov U (2006) Identification and characterization of porcine mannan-binding lectin A (pMBL-A), and determination of serum concentration heritability. Immunogenetics 58:129–137

    Article  PubMed  CAS  Google Scholar 

  • Juul-Madsen HR, Kjærup RM, Toft C, Henryon M, Heegaard PMH, Berg P, Dalgaard TS (2011) Structural gene variants in the porcine mannose-binding lectin 1 (MBL1) gene are associated with low serum MBL-A concentrations. Immunogenetics. doi:10.1007/s00251-011-0512-1

  • Koppenheffer TL, Spong KD, Falvo HM (1998) The complement system of the marsupial Monodelphis domestica. Dev Comp Immunol 22:231–237

    Article  PubMed  CAS  Google Scholar 

  • Larionov A, Krause A, Miller W (2005) A standard curve based method for relative real time PCR data processing. BMC Bioinformatics 6:62–78

    Article  PubMed  Google Scholar 

  • Li ZM, Zhang SC, Wang CF, Pang QX (2008) Complement-mediated killing of Vibrio species by the humoral fluids of amphioxus Branchiostoma belcheri: implications for a dual role of O-antigens in the resistance to bactericidal activity. Fish Shellfish Immunol 24:215–222

    Article  PubMed  Google Scholar 

  • Lillie BN, Keirstead ND, Squires EJ, Hayes MA (2006a) Single-nucleotide polymorphisms in porcine mannan-binding lectin A. Immunogenetic 58:983–993

    Article  CAS  Google Scholar 

  • Lillie BN, Hammermueller JD, MacInnes JI, Jacques M, Hayes MA (2006b) Porcine mannan-binding lectin A binds to Actinobacillus suis and Haemophilus parasuis. Dev Comp Immunol 30:954–965

    Article  PubMed  CAS  Google Scholar 

  • Lillie BN, Keirstead ND, Squires EJ, Hayes MA (2007) Gene polymorphisms associated with reduced hepatic expression of porcine mannan-binding lectin C. Dev Comp Immunol 31:830–846

    Article  PubMed  CAS  Google Scholar 

  • Lipscombe RJ, Sumiya M, Hill AVS, Lau YL, Levinsky RJ, Summerfield JA, Turner MW (1992) High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1:709–715

    Article  PubMed  CAS  Google Scholar 

  • Lipscombe RJ, Sumiya M, Summerfield JA, Turner MW (1995) Distinct physiochemical characteristics of human mannose-binding protein expressed by individuals of differing genotype. Immunology 85:660–667

    PubMed  CAS  Google Scholar 

  • Loveless RW, Feizi T, Childs TRA, Mizuochi T, Stoll MS, Oldroyd RG, Lachmann PJ (1989) Bovine serum conglutinin is a lectin which binds non-reducing terminal N-acetylglucosamine, mannose and fucose residues. Biochem J 258:109–113

    PubMed  CAS  Google Scholar 

  • Lutz HU, Jelezarova E (2006) Complement amplification revisited. Mol Immunol 43:2–12

    Article  PubMed  CAS  Google Scholar 

  • Maas J, de Roda Husman AM, Brouwer M, Brouwer M, Krol A, Coutinho R, Keet I, van Leeuwen R, Schuitemaker H (1998) Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. Amsterdam Cohort Study. AIDS 12:2275–2280

    Article  PubMed  CAS  Google Scholar 

  • Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, Svejgaard A (1995) Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 155:3013–3020

    PubMed  CAS  Google Scholar 

  • Madsen HO, Satz ML, Hogh B, Svejgaard A, Garred P (1998) Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. J Immunol 161:3169–3175

    PubMed  CAS  Google Scholar 

  • Mason C (2006) Basic mastitis bacteriology: untangling the pathogens. Irish Vet J 59:453–459

    Google Scholar 

  • Matheswaran K, Dhinakar Raj G, Nachimuthu K (2003) Demonstration of alternative and classical complement pathway activity in colostrum from Buffalo. Vet Res Commun 27:445–452

    Article  PubMed  CAS  Google Scholar 

  • Miller MP (1997) Tools for population genetic analyses (TFPGA) 1.3: a Windows program for the analysis of allozyme and molecular population genetic data. http://www.marksgeneticsoftware.net/_vti_bin/shtml.exe/tfpga.htm

  • Miller GY, Bartlett PC, Lance SE, Anderson J, Heider LE (1993) Costs of clinical mastitis and mastitis prevention in dairy herds. J Am Vet Med Assoc 202:1230–1236

    PubMed  CAS  Google Scholar 

  • Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW (2000) Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 68:688–693

    Article  PubMed  CAS  Google Scholar 

  • Oswald IP, Lantier F, Bourgy G (1990) Classical and alternative pathway hemolytic activities of ovine complement: variations with age and sex. Vet Immunol Immunopathol 24:259–266

    Article  PubMed  CAS  Google Scholar 

  • Oviedo-Boyso J, Valdez-Alarcón JJ, Cajero-Juarez M, Ochoa-Zarzosa A, López-Meza JE, Bravo-Patiño A, Baizabal-Aguirre VM (2007) Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis. J Infect 54:399–409

    Article  PubMed  Google Scholar 

  • Petersen SV, Thiel S, Jensenius JC (2001) The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 38:133–149

    Article  PubMed  CAS  Google Scholar 

  • Phatsara C, Jennen DGJ, Ponsuksili S, Murani E, Tesfaye D, Schellander K, Wimmers K (2007) Molecular genetic analysis of porcine mannose-binding lectin genes, MBL1 and MBL2, and their association with complement activity. Int J Immunogenet 34:55–63

    Article  PubMed  CAS  Google Scholar 

  • Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ (2000) Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 76:227–324

    Article  PubMed  CAS  Google Scholar 

  • Podolsky MJ, Lasker A, Flaminio MJBF, Gowda LD, Ezekowitz RAB, Takahashi K (2006) Characterization of an equine mannan-binding lectin and its roles in disease. Biochem Bioph Res Com 343:928–936

    Article  CAS  Google Scholar 

  • Qiu H (2002) Modern dairy science. Agriculture Press of China, Beijing, pp 1–12

    Google Scholar 

  • Rosenfeld SI, Baum J, Steigbigel RT, Leddy JP (1976) Hereditary deficiency of the fifth component of complement in man. II. Biological properties of C5-deficient human serum. J Clin Invest 57:1635–1643

    Article  PubMed  CAS  Google Scholar 

  • Rupp R, Boichard D (1999) Genetic parameters for clinical mastitis, somatic cell score, production, udder type traits and milking ease in first lactation Holsteins. J Dairy Sci 82:2198–2204

    Article  PubMed  CAS  Google Scholar 

  • Seegers H, Fourichon C, Beaudeau F (2003) Production effects related to mastitis and mastitis economics in dairy cattle herds. Vet Res 34:475–491

    Article  PubMed  Google Scholar 

  • Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98

    Article  PubMed  CAS  Google Scholar 

  • Shi L, Takahashi K, Dundee J, Shahroor-Karni S, Thiel S, Jensenius JC, Gad F, Hamblin MR, Sastry KN, Ezekowitz RA (2004) Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus. J Exp Med 199:1379–1390

    Article  PubMed  CAS  Google Scholar 

  • Shook GE, Schutz MM (1994) Selection on somatic cell score to improve resistance to mastitis in the United States. J Dairy Sci 77:648–658

    Article  PubMed  CAS  Google Scholar 

  • Stear MJ, Bisshop SC, Mallard BA, Raadsma H (2001) The sustainability, feasibility and desirability of breeding livestock for disease resistance. Res Vet Sci 71:1–7

    Article  PubMed  CAS  Google Scholar 

  • Sumiya M, Super M, Tabona P, Levinsky RJ, Arai T, Turner MW, Summerfield JA (1991) Molecular basis of opsonic defect in immunodeficient children. Lancet 337:1569–1570

    Article  PubMed  CAS  Google Scholar 

  • Swanson KM, Stelwagen K, Davis SR, Henderson HV, Davis SR, Farr VC, Singh K (2009) Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model. J Dairy Sci 92:117–129

    Article  PubMed  CAS  Google Scholar 

  • Takahashi R, Tsutsumi A, Ohtani K, Muraki Y, Goto D, Matsumoto I, Wakamiya N, Sumida T (2005) Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus. Ann Rheum Dis 64:311–314

    Article  PubMed  CAS  Google Scholar 

  • Tan YJ, Liu LF, Luo P, Wang A, Jia T, Shen X, Wang M, Zhang S (2009) Association between mannose-binding lectin and HIV infection and progression in a Chinese population. Mol Immunol 47:632–638

    Article  PubMed  CAS  Google Scholar 

  • Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U, Reid KB, Jensenius JC (1997) A second serine protease associated with mannan-binding lectin that activates complement. Nature 386:506–510

    Article  PubMed  CAS  Google Scholar 

  • Toohey MG, Jones KA (1989) In vitro formation of short RNA polymerase II transcripts that terminate within the HIV-1 and HIV-2 promoter proximal downstream regions. Genes Dev 3:265–282

    Article  PubMed  CAS  Google Scholar 

  • Tsang SY, Nakanishi M, Peterlin BM (1990) Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. Mol Cell Biol 10:711–719

    PubMed  CAS  Google Scholar 

  • van de Wetering JK, van Golde LM, Batenburg JJ (2004) Collectins: players of the innate immune system. Eur J Biochem 271:1229–1249

    Article  PubMed  Google Scholar 

  • Wambura PN, Gwakisa PS, Silayo RS, Rugaimukamu EA (1998) Breed-associated resistance to tick infestation in Bos indicus and their crosses with Bos taurus. Vet Parasitol 77:63–70

    Article  PubMed  CAS  Google Scholar 

  • Wang CF, Gao YD, Yang SH, Wang HM, Zhang Y, Li JB, Hou MH, Zhong JF (2006) Characterization of alternative complement hemolytic pathway activity in Holstein bull serum. Acta Zool Sinica 52:698–705

    CAS  Google Scholar 

  • Wang CF, Liu M, Li QL, Ju ZH, Huang JM, Li JB, Wang HM, Zhong JF (2011) Three novel single-nucleotide polymorphisms of MBL1 gene in Chinese native cattle and their associations with milk performance traits. Vet Immunol Immunolpathol 139:229–236

    Article  CAS  Google Scholar 

  • Xie XH, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M (2005) Systematic discovery of regulatory motifs in human promoters and 3′UTRs by comparison of several mammals. Nature 434:338–345

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Chung EK, Zhou B, Blanchong CA, Yu YC, Fust G, Kovacs M, Vatay A, Szalai C, Karadi I, Varga L (2003) Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. J Immunol 171:2734–2745

    PubMed  CAS  Google Scholar 

  • Yano T (1992) Assays of hemolytic complement activity. In: Stolen JS, Fletcher TC, Anderson DP, Kaattari SL, Rowley AF (eds) Techniques in fish immunology. SOS, Fair Haven, pp 131–142

    Google Scholar 

  • Zhao F, Zhao Z, Yan G, Wang D, Ban Q, Yu P, Zhang WX, Luo Y (2011) Polymorphisms in mannose-binding lectin (MBL) gene and their association with MBL protein levels in serum in the Hu sheep. Vet Immunol Immunopathol 140:297–302

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Anti-TB Transgenic Project (2008ZX08007-004), the National Science and Technology Pillar Program during the 12th Five-Year Plan (2011BAD19B04), the National Natural Science Funds (No. 31000543), the National Cow Industrial Technology System Program (No. CARS-37), and the Key Scientific and Technological Project from Shandong Province (No. 2009GG20002033).

Author information

Authors and Affiliations

  1. Dairy Cattle Research Center, Shandong Academy of Agricultural Science, No. 159 Industry North Road Jinan City, Shandong Province, Jinan, 250100, People’s Republic of China

    Jianbo Liu, Zhihua Ju, Qiuling Li, Jinming Huang, Rongling Li, Jiangbin Li, Jifeng Zhong & Changfa Wang

  2. College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, 130118, People’s Republic of China

    Jianbo Liu

  3. Jilin Agriculture Science and Technology College, Jinlin, 132101, People’s Republic China

    Lijuan Ma

Authors
  1. Jianbo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhihua Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiuling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinming Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rongling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiangbin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lijuan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jifeng Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Changfa Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changfa Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, J., Ju, Z., Li, Q. et al. Mannose-binding lectin 1 haplotypes influence serum MBL-A concentration, complement activity, and milk production traits in Chinese Holstein cattle. Immunogenetics 63, 727–742 (2011). https://doi.org/10.1007/s00251-011-0548-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-011-0548-2

Keywords

Search

Navigation