Allelic polymorphism of Ovar-DRB1 exon2 gene and parasite resistance in two dairy sheep breeds
Vol 3, N 1, 2016


dairy sheep
Greek breeds
Ovar-DRB1 exon2 alleles
genetic polymorphism


The Ovar-DRB1 gene locus is one of the most polymorphic genes of the Major Histocompatibility Complex (Ovar-MHC) and holds a functional role to antigen presentation. The aim of this study was: a) to describe the Ovar-DRB1 locus variability in two dairy Greek sheep breeds and b) to investigate associations between this variability with resistance to gastrointestinal parasitosis. Blood and faecal samples were collected from 231 and 201 animals of Arta and Kalarrytiko breeds, respectively. The identification of alleles was performed using the sequence–base method. Faecal egg counting (FEC) of the gastrointestinal parasites and measures of blood plasma pepsinogen levels were performed in order to evaluate parasitological parameters. From this study in the overall examined animals, thirty-nine Ovar-DRB1 alleles were identified, among them, ten new alleles, reported for the first time in the literature. In Arta breed a total of twenty-four alleles were found. Among the detected alleles, ten were breed specific and five were new. Regarding the Kalarrytiko breed, twenty-nine alleles were found, fifteen of them were unique and nine were new. The studied breeds differed in their allelic profile, with only 12 common from the total of 134 different recorded genotypes. A higher number of animals with high parasitic load and high plasma pepsinogen values were found in Kalarrytiko. Associations between Ovar-DRB1 alleles with FEC values were found with certain heterozygous genotypes to present significantly reduced FEC values. The large number of detected alleles with low frequencies and the fact that the majority of animals were heterozygous, make hard to find strong associations


Abbott, K.A., Taylor, M., Stubbings, LA., 2009. SCOPS (Sustainable Control of Parasites in Sheep), Sustainable Worm Control Strategies for Sheep, A Technical Manual for Veterinary Surgeons and Advisers, 3rd edit. Context Publications.

Andersson, L., Rask, L., 1988. Characterization of the MHC class II region in cattle: The number of DQ genes varies between haplotypes. Immunogenetics 27, 110-120.

Anderson, N., Armour, J., Jarrett, W.F., Jennings, F.W., Ritchie, J.S., Urquhart, G.M., 1965. A field study of parasitic gastritis in cattle. Vet. Rec. 77, 1196-204.

Ballingall, K.T., Tassi, R., 2010. Sequence-based genotyping of the sheep MHC class II DRB1 locus. Immunogenetics 62, 31-39.

Behnke, J.M., Iraqi, F., Menge, D., Baker, R.L., Gibson, J., Wakelin, D., 2003. Chasing the genes that control resistance to gastrointestinal nematodes. J. Helminthol. 77, 99-110.

Behnke, J.M., Iraqi, F.A., Mugambi, J.M., Clifford, S., Nagda, S., Wakelin, D., Kemp, S.J., Baker, R.L., Gibson, J.P., 2006. High resolution mapping of chromosomal regions controlling resistance to gastrointestinal nematode infections in an advanced intercross line of mice. Mamm. Genome 17, 584-597.

Bishop, S.C., Jackson, F., Coop, R.L., Stear, M.J., 2004. Genetic parameters for resistance to nematode infections in Texel lambs and their utility in breeding programmes. Anim. Sci. 78, 185-194.

Bissett, S.A., Vlassoff, A., Morris, C.A., Southey, B.R., Baker, R.L., Parker, A.G.H., 1992. Heritability and genetic correlations among faecal egg counts and productivity traits in Romney sheep. New Zeal. J. Agr. Res. 35, 51-58.

Buitkamp, J., Gostomski, D., Schwaiger, F.W., Stear, M.J., Epplen, J.T., 1994. Association between the ovine major histocompatibility complex DRB1 gene and resistance to Ostertagia circumcincta infestation. Anim. Genet. 25, 59-60.

Charbonnel, N., Pemberton, J., 2005. A long-term genetic survey of an ungulate population reveals balancing selection acting on MHC through spatial and temporal fluctuations in selection. Heredity 95: 377-388.

Charon, K.M., Moskwa, B., Rutkowski, R., Gruszczynska, J., Swiderek, W., 2002. Microsatellite polymorphism in DRB1 gene (MHC class II) and its relation to nematode faecal egg count in Polish Heath sheep. J. Anim. Feed. Sci. 11, 47-58.

Clarke, B., Kirby, D.R., 1996. Maintenance of histocompatibility polymorphisms. Nature 211: 999-1000.

Cutrera A.P., Zenuto, R.R., Lacey, E.A., 2011. MHC variation, multiple simultaneous infections and physiological condition in the subterranean rodent Ctenomys talarum. Infect. Genet. Evol. 11, 5: 1023-1036.

Davies, G., Stear, M.J., Benothman, M., Abuagob, O., Kerr, A., Mitchell, S., Bishop, S.C., 2006. Quantitative trait loci associated with parasite infection in Scottish blackface sheep. Heredity 96, 252-258.

Dukkipati, V.S.R., Blair, H.T., Garrick, D.J., Murray, A., 2006. ‘Ovar-Mhc’ - Ovine major histocompatibility complex: Role in genetic resistance to diseases. New Zeal. Vet. J. 54, 153-160.

Fox, M.T., Pitt, S.R., Gerrelli, D., Jacobs, D.E., Adhikari, D.R., Goddard, P.J., 1988. Use of blood gastrin assay in the diagnosis of ovine haemonchiasis. Vet. Rec. 122, 136-137.

Fremont, D.H., Hendrickson, W.A., Marrack, P., Kappler, J., 1996. Structures of an MHC class II molecule with covalently bound single peptides. Science 272, 1001-1004.

Froeschke, G., Sommer, S., 2005. MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Mol. Biol. Evol. 22, 1254-1259.

Gasbarre, L.C., Leighton, E.A., Davies, C.J., 1993. Influence of host genetics upon antibody responses against gastrointestinal nematode infections in cattle. Vet. Parasitol. 46, 81-91.

Germain, R.N., Margulies, D.H., 1993. The biochemistry and cell biology of antigen processing and presentation. Annu. Rev. Immunol. 11, 403-450.

Gruszczynska, J., 1999. Polymorphism of the OLA-DRB1 (MHC class II) gene in German Merino sheep. Ann. Warsaw Agricult. Univ. - SGGW, Anim. Sci. 35, 125-132.

Gruszczyńska1, J., Brokowska, K., Charon, K.M., Świderek W.P. 2005. Single strand conformation polymorphism in exon 2 of the Ovar-DRB1 gene in two Polish breeds of sheep. Anim. Sci. Papers & Reports vol. 23, no. 3, 207-213.

Hamilton W.D., 1980. Sex versus non-sex versus parasite. Oikos 35: 282-290.

Hassan, M., Good, B., Hanrahan, J.P., Campion, D., Sayers, G., Mulcahy, G., Sweeney, T., 2011. The dynamic influence of the DRB1*1101 allele on the resistance of sheep to experimental Teladorsagia circumcincta infection. Vet. Res. 42, 46.

Hedrick, P.W., Kim, T.J., 1998. Genetics of complex polymorphisms: parasites and maintenance of MHC variation (Evolutionary Genetics from Molecules to Morphology by Singh RS & Krimbas CK, Cambridge University Press, New York).

Hedrick, P.W., 2002. Pathogen resistance and genetic variation at MHC loci. Evolution 56, 1902-1908.

Hirschowitz, B.I., 1955. Pepsinogen in the blood. J. Lab. Clin. Med. 46, 568-579.

Janeway, C.A, Travers, P. 1996. Immunobiology: The Immune System in Health and Disease 2nd ed. Current Biology Publications, London.

Karlsson, L.J.E. Greeff, J.C., 2012. Genetic aspects of sheep parasitic diseases. Veterinary Parasitology 189, 104-112.

Knight, J.S., Baird, D.B., Hein, W.R., Pernthaner, A., 2010. The gastrointestinal nematode Tricostrongylus colubriformis down-regulates immune gene expression in migratory cells in afferent lymph. BMC Immunol. 11, 51.

Konnai, S., Nagaoka, Y., Takesima, S., Onuma, M., Aida, Y., 2003. Sequences and diversity of 17 new Ovar-DRB1 alleles from three breeds of sheep. Eur. J. Immunogenet. 30, 275-282.

Kοrot’ko, G.F., Islyamova, M.E., 1963. Determination of the proteolytic activity of gastric juice, urine, and serum. Sib. Sci. Trans. Andrharsk. Med. Inst. 4, 114-126.

Larruskain, A., Minguijón, E., García-Etxebarria, K., Moreno, B., Arostegui, I., Juste, R.A., Jugo, B.M., 2010. MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi-Visna and pulmonary adenocarcinoma viral diseases in sheep. Immunogenetics 62, 75-83.

Larsen J.W.A., 2014. Sustainable internal parasite control of sheep in Australia. Small Ruminant Research, 118, 41-47.

Lawton, D.E., Reynolds, G.W., Hodgkinson, S.M., Pomroy, W.E., Simpson, H.V., 1996. Infection of sheep with adult and larval Ostertagia circumcincta: effects on abomasal pH and serum gastrin and pepsinogen. Int. J. Parasitol. 26, 1063-74.

Marsh, S.G., Bodmer, J.G., 1993. HLA class II nucleotide sequences, 1992. Immunogenetics 37, 79-94.

McCririe, L., Bairden, K., Britton, C., Buitkamp, J., McKeand, J.B., Stear, M.J., 1997. Heterogeneity in the recognition of Ostertagia circumcincta antigens by serum antibody from mature infected sheep. Parasite Immunol. 19, 235-242.

Mostofa, M., McKellar, Q.A., Eckersall, P.D., Gray, D., 1990. Pepsinogen types in worm-free sheep and in sheep infected with Ostertagia circumcincta and Haemonchus contortus. Res. Vet. Sci. 48, 108-11.

Nei, M., 1978. Estimation of average heterozygosity and genetic distance from a small number of individuals. Genetics 89, 583-90.

Outteridge, P.M., Andersson, L., Douch, P.G.C., Green, R.S., Gwakisa, P.S., Hohenhaus, M.A., Mikko, S., 1996. The PCR typing of MHC-DRB genes in the sheep using primers for an intronic microsatellite: application to nematode parasite resistance. Immunol. Cell Biol. 74, 330-336.

Paterson, S., 1998. Evidence for balancing selection at the major histocompatibility complex in a free-living ruminant. J. Hered. 89, 289-294.

Paterson, S., Wilson, K., Pemberton, J.M., 1998. Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.). P. Natl. Acad Sci. USA 95, 3714-3719.

Rogdakis, E., 2002. Indigenous Sheep Breeds: Description, Fylogeneia, Genetic Improvement, Preservation. Agrotypos Editions (Athens) SA.

Roos, M.H., 1997. The role of drugs in the control of parasitic nematode infections: must we do without? Parasitology 114, 437-438.

Rousset, F., 2008. Genepop'007: A complete reimplementation of the Genepop software for Windows and Linux. Mol. Ecol. Resour. 8, 103-106.

Rudensky, A.Y., Preston-Hurlburt, P., Hong, S.C., Barlow, A., Janeway, C.A., 1991. Sequence analysis of peptides bound to MHC class II molecules. Nature 353, 622-627.

Sayers, G., Good, B., Hanrahan, J.P., Ryan, M., Angles, J.M., Sweeney, T., 2005. Major histocompatibility complex DRB1 gene: its role in nematode resistance in Suffolk and Texel sheep breeds. Parasitology 131, 403-409.

Schwaiger, F.W., Weyers, E., Epplen, C., Brün, J., Ruff, G., Crawford, A., Epplen J.T., 1993. The paradox of MHC-DRB exon/intron evolution: alpha-helix and beta-sheet encoding regions diverge while hypervariable intronic simple repeats coevolve with beta-sheet codons. J. Mol. Evol. 37, 260-272.

Schwaiger, F.W., Weyers, E., Buitkamp, J., Ede A.J., Crawford, A., Epplen, J.T., 1994. Interdependent MHC-DRB exon-plus-intron evolution in artiodactyls. Mol. Biol. Evol. 11, 239-249.

Schwaiger, F.W., Gostomski, D., Stear, M.J., Duncan, J.L., McKellar, Q.A., Epplen J.T., Buitkamp J., 1995. An ovine major histocompatibility complex DRB1 allele is associated with low faecal egg counts following natural, predominantly Ostertagia circumcincta infection. Int. J. Parasitol. 25, 815-822.

Stear, M.J., Tierney, T.J., Baldock, F.C., Brown, S.C., Nicholas, F.W., Rudder, T.H., 1988. Class I antigens of the bovine major histocompatibility system are weakly associated with variation in faecal worm egg counts in naturally infected cattle. Anim. Genet. 19, 115-122.

Stear, M.J., Hetzel, D.J., Brown, S.C., Gershwin, L.J., Mackinnon, M.J., Nicholas, F.W., 1990. The relationships among ecto- and endoparasite levels, class I antigens of the bovine major histocompatibility system, immunoglobulin E levels and weight gain. Vet. Parasitol. 34, 303-321.

Stear, M.J., Bishop, S.C., Doligalska, M., Duncan, J.L., Holmes, P.H., Irvine, J., McCririe, L., McKellar, Q.A., Sinski, E., Murray, M., 1995a. Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta. Parasite Immunol. 17, 643-652.

Stear, M.J., Bishop, S.C., Duncan, J.L., McKellar, Q.A., Murray, M., 1995b. The repeatability of faecal egg counts, peripheral eosinophil counts, and plasma pepsinogen concentrations during deliberate infections with Ostertagia circumcincta. Int. J. Parasitol. 25, 375-380.

Stear, M.J., Bairden, K., Bishop, S.C., Buitkamp, J., Epplen, J.T., Gostomski, D., McKellar, Q.A., Schwaiger, F.W., Wallace, D.S., 1996. An ovine lymphocyte antigen is associated with reduced faecal egg counts in four-month-old lambs following natural, predominantly Ostertagia circumcincta infection. Int. J. Parasitol. 26, 423-428.

Stear, M.J., Bairden, K., Bishop, S.C., Buitkamp, J., Duncan, J.L., Gettinby, G., McKellar, Q.A., Park, M., Parkins, J.J., Reid, S.W., Strain, S., Murray, M., 1997a. The genetic basis of resistance to Ostertagia circumcincta in lambs. Vet. J. 154, 111-119.

Stear, M.J., Bairden, K., Duncan, J.L., Holmes, P.H., McKellar, Q.A., Park, M., Strain, S., Murray, M., Bishop, S.C., Gettinby, G., 1997b. How hosts control worms. Nature 389, 27.

Stear, M.J., Bishop, S.C., Mallard, B.A., Raadsma, H., 2001. The sustainability, feasibility and desirability of breeding livestock for disease resistance. Res. Vet. Sci. 71, 1-7.

Stear, M.J., Innocent, G.T., Buitkamp, J., 2005. The evolution and maintenance of polymorphism in the major histocompatibility complex. Vet. Immunol. Immunop. 108, 53-57.

Takahata, N., Nei, M., 1990. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics. 124: 967-978.

Thienpont, D., Rochette, F., Vanparijs, O.F.J., 1986. Diagnosing Helminthiasis by Coprological Examination. Coprological Examination, 2nd ed. Janssen Research Foundation, Beerse, Belgium, 205 pp.

Thorsby, E., 1999. MHC structure and function. Transpl. P. 31, 713-716.

Yakoob, A.Y., Holmes, P.H., Parkins, J.J., Armour, J., 1983a. Plasma protein loss associated with gastrointestinal parasitism in grazing sheep. Res. Vet. Sci. 34, 58-63.

Yakoob, A.Y., Holmes, P.H., Armour, J., 1983b. Pathophysiology of gastrointestinal trichostrongyles in sheep: plasma losses and changes in plasma pepsinogen levels associated with parasite challenge of immune animals. Res. Vet. Sci. 34, 305-9.

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