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QUANTITATIVE TRAIT LOCI FOR PARASITE RESISTANCE. Sonja Dominik CSIRO Livestock Industries Armidale. BONJOUR!!!. KEY MESSAGES. Parasite resistance is ….a prime trait to investigate on a molecular level ….a very complex trait ….difficult to collect phenotypes for
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QUANTITATIVE TRAIT LOCI FOR PARASITE RESISTANCE Sonja Dominik CSIRO Livestock Industries Armidale
KEY MESSAGES Parasite resistance is ….a prime trait to investigate on a molecular level ….a very complex trait ….difficult to collect phenotypes for ….evidently influenced by major genes
INTRODUCTION Parasite resistance is a prime trait to investigate on a molecular level!
ECONOMIC IMPACT Direct cost ~ AUS$ 50 Million = EURO 30 Million + Indirect Cost ~ AUS$ 250 Million = EURO 150 Million Total Cost ~ AUS$ 300 Million = EURO 180 Million
GENETIC VARIATION Between breed variation
GENETIC VARIATION Within-breed variation allows genetic progress
PARASITE OF MAJOR IMPORTANCE • Haemonchus contortus (Barbers pole) • Trichostrongylus colubriformis / vitrinus (Black scour worm) • Teladorsagia circumcincta (syn Ostertagia or Brown stomach worm)
DIAGRAM OF IMMUNE RESPONSE IgA IgG1 IgE Mucus Peristalsis Goblet cells Antigens Plasma cells Th2 activation Cytokines IL-3, IL-4, IL-5,IL-6, IL-9, IL-10, IL13 Memory B-cells IgG,IgM,IgE Inflammatory mediators Processing / Recognition Mesenteric lymph nodes Recruitment Bone marrow Clonal expansion Plasma cells AB B-cells Mastcells Eosinophils Neutrophils Stemcells Th Clonal expansion EXPULSION OF WORMS Gut mucosa Behnke et al. 2003
INSIGHTS FROM MOUSE EXPERIMENTS • Some key component genes • Large allelic variation • Dominant • Heritability 0.2 – 0.4 • MHC genes responsible for some genetic variation between strains • Interaction between MHC and non-MHC genes
PHENOTYPIC INDICATORS Worm burden • FEC • TWC • Serum antibody • Circulating eosinophils • Packed cell volume • Plasma pepsinogen • Dag score • Faecal consistency score Physiological host response Clinical symptoms (Beh and Maddox 1996)
QTL FOR PARASITE RESISTANCE TRAITS IN SHEEP Segregation analysis H. contortus • Evidence for two QTL based on FEC in ITT x Merino (Raadsma et al. 2002) • Evidence from segregation analysis for QTL based on FEC in Merino (Meszaros et al. 2001)
Chromosome 1 T.colubriformis EPCDV010 – ILSTS044 (Diez-Tascon et al. 2002) T. colubriformis McM130 – McM257 (Beh et al. 2001) 347 cM
Chromosome 3 T. colubriformis TGLA67 – OarVH130 (Beh et al. 2001) Te. circumcincta IFNG region (Coltman et al. 2001) Multiple species IFNG region (Paterson et al. 2002) 308.8 cM
Chromosome 6 T. colubriformis McM140 – McM257 (Beh et al. 2001) 148.7 cM
Chromosome 20 H. contortus OarCP73 BM1815 DYMS1 (Janssen et al. 2002) Te. circumcincta DY locus (Buitkamp et al. 1996) Te. circumcincta MHC-DRB1 (Schwaiger et al. 1995) 89.6 cM
QTL FOR PARASITE RESISTANCE TRAITS IN SHEEP Summary • Evidence of QTL for parasite resistance • Difficult to compare studies – wide range of phenotypes • Most findings do not overlap, but IFNG is a very likely candidate
CSIRO GENE MAPPING FLOCK Merino Granddams Romney Grandsires 1 2 3 4 5 ..... 21 ♂ ♀ ♀ ♀ ♀ ♂ ♀ ♀ ♀ ♀ F1 FS-7 FS-8 FS-1 FS-2 FS-3 FS-4 FS-5 FS-6 1994 - 1996 Total of 15 fullsib groups 172 animals genotyped 1997 HS Progeny 229 animals genotyped
MATERIALS & METHODSPhenotypic data • FEC 3, 4 and 5 • FEC3, FEC4, FEC5 -> total FEC • crFEC3, crFEC4, crFEC5 -> total crFEC • 160 records • Between 28% and 86% of animals infected
MATERIALS & METHODSProtocol • Check phenotypes for possible errors • Check genotype data • Test fixed effects • Check residuals for normality • QTL Express / Rqtl
RESULTS 2.8 2.5 3.8 7.0 3.8 3.1 5.6 3.8 2.1 2.7 2.8 3.2 8.3 2.8 3.7 4.9 5.6 5.7 3.5 5.5 4.6 2.4 3.1 LOD scores for parasite resistance traits Chr. A Chr. B ML NP HK ML NP HK FEC3 crFEC3 FEC4 crFEC4 FEC5 crFEC5 FECtotal crFECtotal
KEY POINTS FROM CSIRO MAPPING FLOCK • Some evidence for QTL for parasite resistance • Data Analysis • Extension of the CSIRO mapping flock will provide more data for closer investigation • Binomial analysis as an alternativeanalysis approach
KEY MESSAGES Parasite resistance is ….a prime trait to investigate on a molecular level ….a very complex trait ….difficult to measure ….evidently influenced by major genes
THE FUTURE • More work on the effects of data quality and analysis method on findings • Combination of candidate gene approaches and mapping studies • Comparative genomics plays an important role