Skip to main content

Advertisement

Log in

Single-nucleotide polymorphisms in CD8A and their associations with T lymphocyte subpopulations in pig

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

Findings from previous studies suggested that the cluster of the differentiation 8 alpha (CD8A) gene plays a prominent role in human T lymphocyte subpopulations. However, the evidence from pig population is still rare. To determine whether the important role of the CD8A gene is conserved in pig, a candidate gene analysis was performed herein through genotype–phenotype associations. Five single-nucleotide polymorphisms (SNPs) locating in the regulatory region of porcine CD8A gene were detected and tested for association analysis with seven T lymphocyte subpopulations (proportion of CD4CD8, CD4+CD8+, CD4+CD8, CD4CD8+, CD4+, CD8+, and the ratio of CD4+ to CD8+ T cells in peripheral blood) in 382 Large White piglets. After Bonferroni correction for multiple testing, four SNPs were significantly associated with some or all of the seven T lymphocyte subpopulations. Analyses of pairwise D’ measures of linkage disequilibrium between all SNPs were also explored. Two haplotype blocks was inferred and the association study on haplotype level revealed similar effects on T lymphocyte subpopulations. In addition, the tissue-specific RNA expression pattern and electrophoretic mobility shift assay offered further explanation of the link between the CD8A gene with porcine T lymphocyte subpopulations. The findings presented here provide strong evidence for associations of CD8A variants with T lymphocyte subpopulations and may be applied in porcine breeding programs.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahmed M, Sternberg A, Hall G, Thomas A, Smith O, O’Marcaigh A, Wynn R, Stevens R, Addison M, King D, Stewart B, Gibson B, Roberts I, Vyas P (2004) Natural history of GATA1 mutations in Down syndrome. Blood 103:2480–2489

    Article  CAS  PubMed  Google Scholar 

  • Akey J, Jin L, Xiong M (2001) Haplotypes vs single marker linkage disequilibrium tests: what do we gain? Eur J Hum Genet 9:291–300

    Article  CAS  PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  PubMed  Google Scholar 

  • Charerntantanakul W, Roth JA (2006) Biology of porcine T lymphocytes. Anim Health Res Rev 7:81–96

    Article  PubMed  Google Scholar 

  • de la Calle-Martin O, Hernandez M, Ordi J, Casamitjana N, Arostegui JI, Caragol I, Ferrando M, Labrador M, Rodriguez-Sanchez JL, Espanol T (2001) Familial CD8 deficiency due to a mutation in the CD8α gene. J Clin Investig 108:117–123

    Article  PubMed Central  PubMed  Google Scholar 

  • Dwivedi V, Manickam C, Binjawadagi B, Linhares D, Murtaugh MP, Renukaradhya GJ (2012) Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions. Virol J 9:45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ellmeier W, Sawada S, Littman DR (1999) The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol 17:523–554

    Article  CAS  PubMed  Google Scholar 

  • Hansen JD, Strassburger P (2000) Description of an ectothermic TCR coreceptor, CD8 alpha, in rainbow trout. J Immunol 164:3132–3139

    Article  CAS  PubMed  Google Scholar 

  • Hansen JD, Zapata AG (1998) Lymphocyte development in fish and amphibians. Immunol Rev 166:199–220

    Article  CAS  PubMed  Google Scholar 

  • Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA, Podkolodny NL, Kolchanov NA (1998) Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 26:362–367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Imagawa S, Yamamoto M, Miura Y (1997) Negative regulation of the erythropoietin gene expression by the GATA transcription factors. Blood 89:1430–1439

    CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Lu X, Liu JF, Gong YF, Wang ZP, Liu Y, Zhang Q (2011) Mapping quantitative trait loci for T lymphocyte subpopulations in peripheral blood in swine. BMC Genet 12:79

    Article  PubMed Central  PubMed  Google Scholar 

  • Lu X, Fu WX, Luo YR, Ding XD, Zhou JP, Liu Y, Liu JF, Zhang Q (2012) Genome-wide association study for T lymphocyte subpopulations in swine. BMC Genom 13:488

    Article  CAS  Google Scholar 

  • Mancebo E, Moreno-Pelayo MA, Mencia A, de la Calle-Martin O, Allende LM, Sivadorai P, Kalaydjieva L, Bertranpetit J, Coto E, Calleja-Antolin S, Ruiz-Contreras J, Paz-Artal E (2008) Gly111Ser mutation in CD8A gene causing CD8 immunodeficiency is found in Spanish Gypsies. Mol Immunol 45:479–484

    Article  CAS  PubMed  Google Scholar 

  • Martin ER, Lai EH, Gilbert JR, Rogala AR, Afshari AJ, Riley J, Finch KL, Stevens JF, Livak KJ, Slotterbeck BD, Slifer SH, Warren LL, Conneally PM, Schmechel DE, Purvis I, Pericak-Vance MA, Roses AD, Vance JM (2000) SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. Am J Hum Genet 67:383–394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moore LJ, Somamoto T, Lie KK, Dijkstra JM, Hordvik I (2005) Characterisation of salmon and trout CD8alpha and CD8beta. Mol Immunol 42:1225–1234

    Article  CAS  PubMed  Google Scholar 

  • Reuter JS, Mathews DH (2010) RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinform 11:129

    Article  Google Scholar 

  • Russell DW, Sambrook J (2006) The condensed protocols from molecular cloning: a laboratory manual. Cold Spring Harbor, New York

    Google Scholar 

  • Scheet P, Stephens M (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78:629–644

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Terry CM, Kling SJ, Cheang KI, Hoidal JR, Rodgers GM (2004) Polymorphisms in the 5′-UTR of the tissue factor gene are associated with altered expression in human endothelial cells. J Thromb Haemost 2:1351–1358

    Article  CAS  PubMed  Google Scholar 

  • Travers P, Walport M, Janeway C, Murphy K (2012) Janeway’s immunobiology, 8th edn. Garland Science, New York

    Google Scholar 

  • Visscher AH, Janss LL, Niewold TA, de Greef KH (2002) Disease incidence and immunological traits for the selection of healthy pigs. Vet Q 24:29–34

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Natarajan K, Margulies DH (2009) Structural basis of the CD8 alpha beta/MHC class I interaction: focused recognition orients CD8 beta to a T cell proximal position. J Immunol 183:2554–2564

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wattrang E, Almqvist M, Johansson A, Fossum C, Wallgren P, Pielberg G, Andersson L, Edfors-Lilja I (2005) Confirmation of QTL on porcine chromosomes 1 and 8 influencing leukocyte numbers, haematological parameters and leukocyte function. Anim Genet 36:337–345

    Article  CAS  PubMed  Google Scholar 

  • Weng L, Macciardi F, Subramanian A, Guffanti G, Potkin SG, Yu Z, Xie X (2011) SNP-based pathway enrichment analysis for genome-wide association studies. BMC Bioinform 12:99

    Article  Google Scholar 

  • Zhang J, Xiang Y, Ding L, Keen-Circle K, Borlawsky TB, Ozer HG, Jin R, Payne P, Huang K (2010) Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia. BMC Bioinform 11(Suppl 9):S5

    Article  Google Scholar 

Download references

Acknowledgments

The authors appreciate the financial support provided by the National High Technology Research and Development Program of China (863 Program 2011AA100302), the National Major Special Project of China on New Varieties Cultivation for Transgenic Organisms (2014ZX0800945B), the National Natural Science Foundations of China (30972092), and the Program for Changjiang Scholars and Innovative Research in University (IRT1191). We are thankful to Muhammmad Zahoor, one of the international students from Pakistan, for proofreading our manuscript.

Conflict of interests

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qin Zhang.

Additional information

Communicated by S. Hohmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, W., Liu, Y., Fu, W. et al. Single-nucleotide polymorphisms in CD8A and their associations with T lymphocyte subpopulations in pig. Mol Genet Genomics 290, 1447–1456 (2015). https://doi.org/10.1007/s00438-015-1008-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-015-1008-8

Keywords

Navigation