Correlation between the Insertion/Deletion Mutations of Prion Protein Gene and BSE Susceptibility and Milk Performance in Dairy Cows

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Abstract

Objective To investigate the 23 bp and 12 bp insertion/deletion (indel) mutations within the bovine prion protein (PRNP) gene in Chinese dairy cows, and to detect the associations of two indel mutations with BSE susceptibility and milk performance.

Methods Based on bovine PRNP gene sequence, two pairs of primers for testing the 23 bp and 12 bp indel mutations were designed. The PCR amplification and agarose electrophoresis were carried out to distinguish the different genotypes within the mutations. Moreover, based on previous data from other cattle breeds and present genotypic and allelic frequencies of two indels mutations in this study, the corrections between the two indel mutations and BSE susceptibility were tested, as well as the relationships between the mutations and milk performance traits were analyzed in this study based on the statistical analyses.

Results In the analyzed Chinese Holstein population, the frequencies of two “del” alleles in 23 bp and 12 bp indel muations were more frequent. The frequency of haplotype of 23del-12del was higher than those of 23del- 12ins and 23ins-12del. From the estimated r2 and D’ values, two indel polymorphisms were linked strongly in the Holstein population (D’ = 57.5%, r2 = 0.257). Compared with the BSE-affected cattle populations from the reported data, the significant differences of genotypic and allelic frequencies were found among present Holstein and some BSE-affected populations (P < 0.05 or P < 0.01). Similarly, there were significant frequency distribution differences of genotypes and alleles among Chinese Holstein and several previous reported healthy dairy cattle (P < 0.05 or P < 0.01). Moreover, association of genotype and combined genotypes of two indel polymorphisms with milk performance and resistant mastitis traits were analyzed in Holstein population, but no significant differences were found (P > 0.05).

Conclusions These observations revealed that the influence of two indel mutations within the bovine PRNP gene on BSE depended on the breed and they did not affect the milk production traits, which layed the foundation for future selection of resistant animals, and for improving health conditions for dairy breeding against BSE in China.

1. Prusiner SB. Prions. Proc Natl Acad Sci USA1998;95:13363-13383.

2. Ibeagha-Awemu EM, Kgwatalala P, Ibeagha AE, Zhao X. A critical analysis of disease-associated DNA polymorphisms in the genes of cattle, goat, sheep, and pig. Mamm Genome 2008;19:226-245.

3. Imran M, Mahmood S, Hussain R, Abid NB, Lone KP. Frequency distribution of PRNP polymorphisms in the Pakistani population. Gene 2012;492:186-194.

4. MeadS, Stumpf MP, Whitfield J, Beck JA, Poulter M, Campbell T, et al. Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 2003;300:640-643.

5. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004;364:527-529.

6. Mercier G, Dieterlen F, Lucotte G. Population distribution of the methionine allele at the PRNP codon 129 polymorphism in Europe and the Middle East. Hum Biol 2008;80:181-190.

7. Lloyd SE, Mead S, Collinge J. Genetics of prion diseases. Curr Opin Genet Dev 2013;23(3):345-351.

8. Goldmann W, Hunter N, Foster JD, SalbaumJM, Beyreuther K, Hope J. Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 1990;87:2476-2480.

9. Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C. Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes.Arch Virol 1996;141:809-824.

10. Babar ME, Farid A, Benkel BF, Ahmad J, Nadeem A, Imran M. Frequencies of PrP genotypes and their implication for breeding against scrapie susceptibility in nine Pakistani sheep breeds. Mol Biol Rep 2009;36:561-565.

11. Tan BC, Blanco AR, Houston EF, Stewart P, Goldmann W, Gill AC, et al. Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene. J Gen Virol 2012;93(Pt 12):2749-2756.

12. Vitezica ZG, Beltran de Heredia I, Ugarte E. Analysis of association between the prion protein (PRNP) locus and milk traits in Latxa dairy sheep. J Dairy Sci 2013;96(9):6079-6083.

13. Goldmann W, Martin T, Foster J, Hughes S, Smith G, Hughes K, et al. Novel polymorphisms in the caprine PrP gene: A codon 142 mutation associated with scrapie incubation period. J Gen Virol 1996;77:2885-2891.

14. Papasavva-Stylianou P, Kleanthous M, Toumazos P, Mavrikiou P, Loucaides P. Novel polymorphisms at codons 146 and 151 in the prion protein gene of Cyprus goats, and their association with natural scrapie. Vet J 2007; 173:459-462.

15. Colussi S, Vaccari G, Maurella C, Bona C, Lorenzetti R, Troiano P, et al. Histidine at codon 154 of the prion protein gene is a risk factor for Nor98 scrapie in goats. J Gen Virol 2008;89:3173-3176.

16. Babar ME, AbdullahM, NadeemA, Haq AU. Prion protein gene polymorphisms in four goat breeds of Pakistan. Mol Biol Rep 2009;36:141-144.

17. Lan XY, Zhao HY, Li ZJ, Li AM, Lei CZ, Chen H, et al. A novel 28-bp insertion-deletion polymorphism within goat PRNP gene and its association with production traits in Chinese native breeds. Genome 2012;55(7): 547-552.

18. Lan X, Zhao H, Wu C, Hu S, Pan C, Lei C, et al. Analysis of genetic variability at codon 42 within caprine prion protein gene in relation to production traits in Chinese domestic breeds. Mol Biol Rep 2012;39(4):4981-4988.

19. Zhou R, Li X, Xi J, Li L, Zhang Z, Zhao Z. Genetic variability of PRNP in Chinese indigenous goats. Biochem Genet 2013;51(3-4):211-222.

20. Acín C, Martín-Burriel I, Monleón E, Lyahyai J, Pitarch JL, Serrano C, et al. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc.). PLoS One 2013; 8(4):e61118.

21. Sander P, Hamann H, Pfeiffer I, Wemheuer W, Brenig B, Groschup MH, et al. Analysis of sequence variability of the bovine prion protein gene (PRNP) in German cattle breeds. Neurogenetics 2004;5:19-25.

22. Cemal U, Kemal O, Nehir O, Dawit T, Ahmet M, Karl S. Detection of bovine spongiform encephalopathy-related prion protein gene promoter polymorphisms in local Turkish cattle. Biochem Genet 2008;46: 820-827.

23. Zhang CL, Chen H, Wang YH, Zhang RF, Lan XY, Lei CZ, et al. Serotonin receptor 1B (HTR1B) genotype associated withmilk production traits in cattle. Res Vet Sci 2008;85:265-268.

24. Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual, vol.3, third ed. Cold Spring Harbor Laboratory Press, New York 2001; p49-56.

25. Lewontin RC. On measures of gametic disequilibrium. Genetics 1988;120: 849-852.

26. Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, et al. A partitionligation- combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis. Cell Res 2009;19(4):519-523.

27. Juling K, Schwarzenbacher H, Williams JL, Fries R. A major genetic component of BSE susceptibility. BMC Biol 2006;4:33.

28. Nakamitsu S, Miyazawa T, Horiuchi M, Onoe S, Ohoba Y, Kitagawa H, et al. Sequence variation of bovine prion protein gene in Japanese cattle (Holstein and Japanese Black). J Vet Med Sci 2006;68(1):27-33.

29. Novakofski J, Brewer MS, Mateus-Pinilla N, Killefer J, McCusker RH. Prion biology relevant tobovine spongiform encephalopathy. J Anim Sci 2006;83:1455-1476.

30. Czarnik U, Zabolewicz T, Strychalski J, Grzybowski G, Bogusz M, Walawski K. Deletion/insertion polymorphism of the prion protein gene (PRNP) in Polish Holstein-Friesian cattle. J Appl Genet 2007;48(1):69-71.

31. Haase B, Doherr MG, Seuberlich T, Drögemüller C, Dolf G, Nicken P, et al. PRNP promoter polymorphisms are associated with BSE susceptibility in Swiss and German cattle. BMC Genet 2007;8:15.

32. Kashkevich K, Humeny A, Ziegler U, Groschup MH, Nicken P, Leeb T, et al. Functional relevance of DNA polymorphisms within the promoter region of the prionprotein gene and their association to BSE infection. FASEB J 2007;21:1547-1555.

33. Muramatsu Y, Sakemi Y, Horiuchi M, Ogawa T, Suzuki K, Kanameda M, et al. Frequencies of PRNP gene polymorphisms in Vietnamese dairy cattle for potential association with BSE. Zoonoses Public Health 2008;55:267-273.

34. Bossers A, Schreuder BE, Muileman IH, Belt PB, Smits MA. PrP genotype contributes to determining survival times of sheep with natural scrapie. J Gen Virol 1996;77 (10):2669-2673.

35. Vilotte JL, Soulier S, Essalmani R, Stinnakre MG, Vaiman D, Lepourry L, et al. Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol 2001;75:5977-5984.

36. Sander P, Hamann H, Dro¨gemu¨ller C, Kashkevich K, Schiebel K, Leeb T. Bovine prion protein gene (PRNP) promoter polymorphisms modulate PRNP expressionand may be responsible for differences in bovinespongiform encephalopathy susceptibility. J Biol Chem 2005;280: 37408-37414.

37. Seabury CM, Womack JE, Pedrahita J, Derr JN. Comparative PRNP genotyping of U.S. cattle siresfor potential association with BSE. Mamm Genome 2004; 15(10):828-833.

38. Brunelle BW, Hamir AN, Baron T, Biacabe AG, Richt JA, Kunkle RA, et al. Polymorphisms of the prion gene promoter region that influence classical bovine spongiform encephalopathy susceptibility are not applicable to other transmissible spongiform encephalopathies in cattle. J Anim Sci 07;85:3142-3147.

39. Kerber AR, Hepp D, Passos DT, Weimer TD. Polymorphisms of two indels at the PRNP gene in three beef cattle herds. Biochem Genet 2008;46:1-7.

40. Ioannides IM, Mavrogenis AP, Papachristoforou C. Analysis of PrP genotypes in relation to reproductive and production traits in Chios sheep. Livest Sci 2009;122(2-3):296-301.

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