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A microsatellite polymorphism in the gamma interferon gene is associated with resistance to gastrointestinal nematodes in a naturally-parasitized population of Soay sheep

Published online by Cambridge University Press:  07 August 2001

D. W. COLTMAN ,
K. WILSON ,
J. G. PILKINGTON ,
M. J. STEAR  and
J. M. PEMBERTON
D. W. COLTMAN
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK
K. WILSON
Affiliation:
Institute of Biological Sciences, University of Stirling, Stirling FK9 4LA, UK
J. G. PILKINGTON
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK
M. J. STEAR
Affiliation:
Glasgow University Veterinary School, Glasgow G61 1QH, UK
J. M. PEMBERTON
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK
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Abstract

Free-living Soay sheep (Ovis aries) on the island of Hirta, St Kilda, Scotland, are naturally parasitized by gastrointestinal nematodes, predominantly Teladorsagia circumcincta. In this paper we show that reduced faecal egg counts (FEC) are associated with an allele at a microsatellite locus located in the first intron of the interferon gamma gene (o(IFN)-γ) in Soay sheep lambs and yearlings, measured at approximately 4 and 16 months of age, respectively. The same allele was also associated with increased T. circumcincta-specific antibody (IgA) in lambs, but not associated significantly in yearlings. Flanking control markers failed to show a significant association with either FEC or IgA. These results suggest that a polymorphic gene conferring increased resistance to gastrointestinal nematode parasites is located at or near the interferon gamma gene, and support previous reports which have mapped a quantitative trait locus (QTL) for resistance to this region in domestic sheep. Our data are consistent with the idea that a functional polymorphism leading to reduced expression or efficacy of (IFN)-γ could enhance the immune response to gastrointestinal nematodes by favouring the activity of the Th2 cell subset and antibody associated immune mechanisms.

Keywords

cytokinehelminthimmunityOvis ariesparasite
Type
Research Article
Information
Parasitology , Volume 122 , Issue 5 , May 2001 , pp. 571 - 582
Copyright
2001 Cambridge University Press

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References

ALLISON, D. B. (1997). Transmission-disequilibrium tests for quantitative traits. American Journal of Human Genetics 60, 676–690.Google Scholar
BANCROFT, D. R., PEMBERTON, J. M. & KING, P. (1995). Extensive protein and microsatellite variability in an isolated, cyclic ungulate population. Heredity 74, 326–336.CrossRefGoogle Scholar
BEH, K. J. & MADDOX, J. F. (1996). Prospects for development of genetic markers for resistance to gastrointestinal parasite infection in sheep. International Journal for Parasitology 26, 879–897.CrossRefGoogle Scholar
BISHOP, S. C., BAIRDEN, K., MCKELLAR, Q. A., PARK, M. & STEAR, M. J. (1996). Genetic parameters for faecal egg count following mixed, natural, predominantly Ostertagia circumcincta infection and relationships with live weight in young lambs. Animal Science 63, 423–428.CrossRefGoogle Scholar
CLUTTON-BROCK, T. H., PRICE, O. F., ALBON, S. D. & JEWELL, P. (1991). Persistent instability and population regulation in Soay sheep. Journal of Animal Ecology 54, 831–846.CrossRefGoogle Scholar
CLUTTON-BROCK, T. H., PRICE, O. F., ALBON, S. D. & JEWELL, P. (1992). Early development and population fluctuations in Soay sheep. Journal of Animal Ecology 61, 381–396.CrossRefGoogle Scholar
COLTMAN, D. W., BANCROFT, D. R., ROBERTSON, A., SMITH, J. A., CLUTTON-BROCK, T. H. & PEMBERTON, J. M. (1999a). Male reproductive success in a promiscuous mammal: behavioural estimates compared with genetic paternity. Molecular Ecology 8, 1199–1209.Google Scholar
COLTMAN, D. W., PILKINGTON, J. G., SMITH, J. A. & PEMBERTON, J. M. (1999b). Parasite-mediated selection against inbred Soay sheep in a free-living, island population. Evolution 53, 1259–1267.Google Scholar
CRAWFORD, A. M. & MCEWEN, J. C. (1998). Identification of Animals Resistant to Nematode Parasite Infection. New Zealand Provisional Patent 330201. New Zealand.
CRAWFORD, A. M., PHUA, S. H., MCEWAN, J. C., DODDS, K. G., WRIGHT, C. C., MORRIS, C. A., BISSET, S. A. & GREEN, R. S. (1997). Finding disease resistance QTL in sheep. Animal Biotechnology 8, 13–22.CrossRefGoogle Scholar
CRAWLEY, M. J. (1993). GLIM for Ecologists. Blackwell Scientific Publications, Oxford.
DE GORTARI, M. J., FREKING, B. A., CUTHBERTSON, R. P., KAPPES, S. M., KEELE, J. W., STONE, R. T., LEYMASTER, K. A., DODDS, K. G., CRAWFORD, A. M. & BEATTIE, C. W. (1998). A second-generation linkage map of the sheep genome. Mammalian Genome 9, 204–209.CrossRefGoogle Scholar
ELSE, K. J. & FINKELMAN, F. D. (1998). Intestinal nematode parasites, cytokines and effector mechanisms. International Journal for Parasitology 28, 1145–1158.CrossRefGoogle Scholar
ELSE, K. J., FINKELMAN, F. D., MALISZEWSKI, C. R. & GRENCIS, R. K. (1994). Cytokine-mediated regulation of chronic intestinal helminth infection. Journal of Experimental Medicine 179, 347–351.CrossRefGoogle Scholar
FINKELMAN, F. D. & MORRIS, S. C. (1999). Development of an assay to measure in vivo cytokine production in the mouse. International Immunology 11, 1811–1818.CrossRefGoogle Scholar
GOLDAMMER, T., BRUNNER, R. M., SCHMIDT, P. & SCHWERIN, M. (1996). Mapping of the interferon gamma gene (IFNG) to chromomes 3 in sheep and 5 in goat by FISH. Mammalian Genome 7, 470–471.CrossRefGoogle Scholar
GRENCIS, R. K. (1997). Th2-mediated host protective immunity to intestinal nematode infections. Philosophical Transactions of the Royal Society, Series B-Biological Sciences 352, 1377–1384.CrossRefGoogle Scholar
GRENFELL, B. T., PRICE, O. F., ALBON, S. D. & CLUTTON-BROCK, T. H. (1992). Overcompensation and population cycle in an ungulate. Nature, London 355, 823–826.CrossRefGoogle Scholar
GRENFELL, B. T., WILSON, K., FINKENSTADT, B. F., COULSON, T. N., MURRAY, S., ALBON, S. D., PEMBERTON, J. M., CLUTTON-BROCK, T. H. & CRAWLEY, M. J. (1998). Noise and determinism in synchronized sheep dynamics. Nature, London 394, 674–677.CrossRefGoogle Scholar
GULLAND, F. M. D. (1992). The role of nematode parasites in Soay sheep (Ovis aries L.) mortality during a population crash. Parasitology 105, 493–503.Google Scholar
GULLAND, F. M. D., ALBON, S. D., PEMBERTON, J. M., MOORCROFT, P. R. & CLUTTON-BROCK, T. H. (1993). Parasite-associated polymorphism in a cyclic ungulate population. Proceedings of the Royal Society, B 254, 7–13.CrossRefGoogle Scholar
GULLAND, F. M. D. & FOX, M. (1992). Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda. Parasitology 105, 481–492.CrossRefGoogle Scholar
ILLIUS, A. W., ALBON, S. D., PEMBERTON, J. M., GORDON, I. J. & CLUTTONBROCK, T. H. (1995). Selection for foraging efficiency during a population crash in Soay sheep. Journal of Animal Ecology 64, 481–492.CrossRefGoogle Scholar
ISHIKAWA, N., GOYAL, P. K., MAHIDA, Y. R., LI, K. F. & WAKELIN, D. (1998). Early cytokine responses during intestinal parasitic infections. Immunology 93, 257–263.CrossRefGoogle Scholar
MINISTRY OF AGRICULTURE, FISHERIES AND FOOD (1971). Manual of Veterinary Parasitological Laboratory Techniques. HMSO, London.Google Scholar
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.). Proceedings of the National Academy of Sciences, USA 95, 3714–3719.CrossRefGoogle Scholar
PEMBERTON, J. M., COLTMAN, D. W., SMITH, J. A. & PILKINGTON, J. G. (1999). Molecular analysis of a promiscuous, fluctuating mating system. Biological Journal of the Linnean Society 68, 289–301.CrossRefGoogle Scholar
PIERSON, C. A., HANRAHAN, V., EDE, A. J. & CRAWFORD, A. M. (1993). Ovine microsatellites at the OarVH34, OarVH41, OarVH58, OarVH61 and OarVH72 loci. Animal Genetics 24, 224.CrossRefGoogle Scholar
PRICHARD, R. (1994). Anthelmintic resistance. Veterinary Parasitology 54, 259–268.CrossRefGoogle Scholar
PRITCHARD, D. I., HEWITT, C. & MOQBEL, R. (1997). Relationship between immunological responsiveness controlled by T-helper 2 lymphocytes and infections with parasitic helminths. Parasitology 115, S33–S44.CrossRefGoogle Scholar
RABINOWITZ, D. (1997). A transmission disequilibrium test for quantitative trait loci. Human Heredity 47, 342–350.CrossRefGoogle Scholar
RAYMOND, M. & ROUSSET, F. (1995). Genepop (Version-1.2)–Population–genetics software for exact tests and ecumenicism. Journal of Heredity 86, 248–249.Google Scholar
READ, A. F., ALBON, S. D., ANTONOVICS, J., APANIUS, V., DWYER, G., HOLT, R. D., JUDSON, O., LIVELY, C. M., MARTIN-LOF, A., MCLEAN, A. R., METZ, J. A. J., SCHMID-HEMPEL, P., THRALL, P. H., VIA, S. & WILSON, K. (1995). Group report: genetics and evolution of infectious diseases in natural populations. In Ecology of Infectious Diseases in Natural Populations (ed. GRENFELL, B. T. & DOBSON, A. P.), pp. 450–477. Cambridge University Press, Cambridge.CrossRef
RICE, W. R. (1989). Analyzing tables of statistical tests. Evolution 43, 223–225.CrossRefGoogle Scholar
ROOS, M. H. (1997). The role of drugs in the control of parasitic nematode infections: must we do without? Parasitology 114, S137–S144.Google Scholar
SCHMIDT, P., LUDT, C., KUHN, C. & BUITKAMP, J. (1996). A diallelic tetranucleotide repeat, (GT(3))(5 or 6), within intron 1 of the ovine interferon-gamma gene. Animal Genetics 27, 437–438.Google Scholar
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 fecal egg counts following natural, predominantly Ostertagia circumcincta infection. International Journal for Parasitology 25, 815–822.CrossRefGoogle Scholar
SINSKI, E., BAIRDEN, K., DUNCAN, J. L., EISLER, M. C., HOLMES, P. H., MCKELLAR, Q. A., MURRAY, M. & STEAR, M. J. (1995). Local and plasma antibody responses to the parasitic larval stages of the abomasal nematode Ostertagia circumcincta. Veterinary Parasitology 59, 107–118.CrossRefGoogle Scholar
SMITH, J. A., WILSON, K., PILKINGTON, J. G. & PEMBERTON, J. M. (1999). Heritable variation in resistance to gastro-intestinal nematodes in an unmanaged mammal population. Proceedings of the Royal Society, B 266, 1283–1290.CrossRefGoogle Scholar
SMITH, T. P. L., LOPEZ-CORRALE, N., GROSZ, M. D., BEATTIE, C. W. & KAPPE, S. M. (1997). Anchoring of bovine chromosomes 4, 6, 7, 10, and 14 linkage group telomeric ends via FISH analysis of lambda clones. Mammalian Genome 8, 333–336.CrossRefGoogle Scholar
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. (1997). How hosts control worms. Nature, London 389, 27.CrossRefGoogle Scholar
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. (1995). Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta. Parasite Immunology 17, 643–652.CrossRefGoogle Scholar
STEAR, M. J., PARK, M. & BISHOP, S. C. (1996). The key components of resistance to Ostertagia circumcincta in lambs. Parasitology Today 12, 438–441.CrossRefGoogle Scholar
STEAR, M. J., STRAIN, S. & BISHOP, S. C. (1999a). How lambs control infection with Ostertagia circumcincta. Veterinary Immunology and Immunopathology 72, 213–218.Google Scholar
STEAR, M. J., STRAIN, S. & BISHOP, S. C. (1999b). Mechanisms underlying resistance to nematode infection. International Journal for Parasitology 29, 51–56.Google Scholar
STEVENSON, I. R. & BANCROFT, D. R. (1995). Fluctuating trade-offs favour precocial maturity in male Soay sheep. Proceedings of the Royal Society, B 262, 267–275.CrossRefGoogle Scholar
STEWART, G. L., NA, H., SMART, L. & SEELIG, L. L. (1999). The temporal relationship among anti-parasite immune elements expressed during the early phase of infection of the rat with Trichinella spiralis. Parasitology Research 85, 672–677.CrossRefGoogle Scholar
WAKELIN, D. (1996). Immunity to Parasites: How Parasitic Infections are Controlled. Cambridge University Press, Cambridge.
WEIR, B. S. (1979). Inferences about linkage disequilibrium. Biometrics 35, 235–254.CrossRefGoogle Scholar
WILSON, K. & GRENFELL, B. T. (1997). Generalized linear modelling for parasitologists. Parasitology Today 13, 33–38.CrossRefGoogle Scholar
WILSON, K., GRENFELL, B. T. & SHAW, D. J. (1996). Analysis of aggregated parasite distributions: A comparison of methods. Functional Ecology 10, 592–601.CrossRefGoogle Scholar
WOOLASTON, R. R. & BAKER, R. L. (1996). Prospects of breeding small ruminants for resistance to internal parasites. International Journal for Parasitology 26, 845–855.CrossRefGoogle Scholar