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

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.

[1]  C. Pierson,et al.  Ovine microsatellites at the OarVH34, OarVH41, OarVH58, OarVH61 and OarVH72 loci. , 2009, Animal genetics.

[2]  R C Elston,et al.  Transmission/disequilibrium tests for quantitative traits , 2001, Genetic epidemiology.

[3]  S. Bishop,et al.  How lambs control infection with Ostertagia circumcincta. , 1999, Veterinary immunology and immunopathology.

[4]  F. Finkelman,et al.  Development of an assay to measure in vivo cytokine production in the mouse. , 1999, International immunology.

[5]  D. Coltman,et al.  Molecular analysis of a promiscuous, fluctuating mating system , 1999 .

[6]  D. Coltman,et al.  PARASITE‐MEDIATED SELECTION AGAINST INBRED SOAY SHEEP IN A FREE‐LIVING ISLAND POPULATON , 1999, Evolution; international journal of organic evolution.

[7]  T. Clutton‐Brock,et al.  Male reproductive success in a promiscuous mammal: behavioural estimates compared with genetic paternity , 1999, Molecular ecology.

[8]  G. Stewart,et al.  The temporal relationship among anti-parasite immune elements expressed during the early phase of infection of the rat with Trichinella spiralis , 1999, Parasitology Research.

[9]  J. Smith,et al.  Heritable variation in resistance to gastro-intestinal nematodes in an unmanaged mammal population , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[10]  T. Clutton‐Brock,et al.  Noise and determinism in synchronized sheep dynamics , 1998, Nature.

[11]  F. Finkelman,et al.  Intestinal nematode parasites, cytokines and effector mechanisms. , 1998, International journal for parasitology.

[12]  J. Pemberton,et al.  Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.) , 1998 .

[13]  Y. Mahida,et al.  Early cytokine responses during intestinal parasitic infections , 1998, Immunology.

[14]  D. Pritchard,et al.  The relationship between immunological responsiveness controlled by T-helper 2 lymphocytes and infections with parasitic helminths , 1997, Parasitology.

[15]  R. Grencis Th2-mediated host protective immunity to intestinal nematode infections. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[16]  G. Gettinby,et al.  How hosts control worms , 1997, Nature.

[17]  D Rabinowitz,et al.  A transmission disequilibrium test for quantitative trait loci. , 1997, Human heredity.

[18]  M. Roos The role of drugs in the control of parasitic nematode infections: must we do without? , 1997, Parasitology.

[19]  J. McEwan,et al.  Finding disease resistance QTL in sheep , 1997 .

[20]  D. Allison,et al.  Transmission-disequilibrium tests for quantitative traits. , 1997, American journal of human genetics.

[21]  Q. Mckellar,et al.  Genetic parameters for faecal egg count following mixed, natural, predominantly Ostertagia circumcincta infection and relationships with live weight in young lambs , 1996 .

[22]  S. Bishop,et al.  The key components of resistance to Ostertagia circumcincta in lambs. , 1996, Parasitology today.

[23]  Bryan T. Grenfell,et al.  Analysis of aggregated parasite distributions: A comparison of methods , 1996 .

[24]  D. Wakelin Immunity to Parasites: How Parasitic Infections are Controlled , 1996 .

[25]  J. Maddox,et al.  Prospects for development of genetic markers for resistance to gastrointestinal parasite infection in sheep. , 1996, International journal for parasitology.

[26]  R. Baker,et al.  Prospects of breeding small ruminants for resistance to internal parasites. , 1996, International journal for parasitology.

[27]  D. Bancroft,et al.  Fluctuating trade-offs favour precocial maturity in male Soay sheep , 1995, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[28]  Q. Mckellar,et al.  Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta , 1995, Parasite immunology.

[29]  Q. Mckellar,et al.  Local and plasma antibody responses to the parasitic larval stages of the abomasal nematode Ostertagia circumcincta. , 1995, Veterinary parasitology.

[30]  T. Clutton‐Brock,et al.  Selection for foraging efficiency during a population crash in Soay sheep , 1995 .

[31]  Q. Mckellar,et al.  An ovine major histocompatibility complex DRB1 allele is associated with low faecal egg counts following natural, predominantly Ostertagia circumcincta infection. , 1995, International journal for parasitology.

[32]  François Rousset,et al.  GENEPOP (version 1.2): population genetic software for exact tests and ecumenicism , 1995 .

[33]  J. Pemberton,et al.  Extensive protein and microsatellite variability in an isolated, cyclic ungulate population , 1995, Heredity.

[34]  Michael J. Crawley,et al.  GLIM for Ecologists , 1994 .

[35]  F. Finkelman,et al.  Cytokine-mediated regulation of chronic intestinal helminth infection , 1994, The Journal of experimental medicine.

[36]  T. Clutton‐Brock,et al.  Parasite-associated polymorphism in a cyclic ungulate population , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[37]  F. Gulland,et al.  Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda , 1992, Parasitology.

[38]  F. Gulland The role of nematode parasites in Soay sheep (Ovis aries L.) mortality during a population crash , 1992, Parasitology.

[39]  P. A. Jewell,et al.  Early development and population fluctuations in Soay sheep , 1992 .

[40]  O. F. Price,et al.  Overcompensation and population cycles in an ungulate , 1992, Nature.

[41]  P. A. Jewell,et al.  Persistent instability and population regulation in Soay sheep , 1991 .

[42]  W. Rice ANALYZING TABLES OF STATISTICAL TESTS , 1989, Evolution; international journal of organic evolution.

[43]  T. Clutton‐Brock,et al.  Population regulation in male and female red deer , 1985 .

[44]  B. Weir Inferences about linkage disequilibrium. , 1979, Biometrics.

[45]  K. Friedhoff Manual of veterinary parasitological laboratory techniques: Ministry of Agriculture, Fisheries and Food, Agricultural Development and Advisory Service, Technical Bulletin No. 18, 2nd edition, 1977, iii + 129 pp., 16 figs., XI plates, 9 tables, Price £3.50 , 1978 .

[46]  S. Bishop,et al.  Mechanisms underlying resistance to nematode infection. , 1999, International journal for parasitology.

[47]  B T Grenfell,et al.  Generalized linear modelling for parasitologists. , 1997, Parasitology today.

[48]  M. Schwerin,et al.  Mapping of the interferon gamma gene (IFNG) to chromosomes 3 in sheep and 5 in goat by FISH. , 1996, Mammalian genome : official journal of the International Mammalian Genome Society.

[49]  C. Kühn,et al.  A diallelic tetranucleotide repeat, (GT3)5 or 6, within intron 1 of the ovine interferon-gamma-gene. , 1996, Animal genetics.

[50]  R. Prichard Anthelmintic resistance. , 1994, Veterinary parasitology.