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      Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees

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          Abstract

          Background

          Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes.

          Results

          Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites.

          Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23.

          Conclusion

          Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion.

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          Most cited references59

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          Drug resistance in nematodes of veterinary importance: a status report.

          Ray Kaplan (2004)
          Reports of drug resistance have been made in every livestock host and to every anthelmintic class. In some regions of world, the extremely high prevalence of multi-drug resistance (MDR) in nematodes of sheep and goats threatens the viability of small-ruminant industries. Resistance in nematodes of horses and cattle has not yet reached the levels seen in small ruminants, but evidence suggests that the problems of resistance, including MDR worms, are also increasing in these hosts. There is an urgent need to develop both novel non-chemical approaches for parasite control and molecular assays capable of detecting resistant worms.
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            Construction of multilocus genetic linkage maps in humans.

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              Confidence intervals in QTL mapping by bootstrapping.

              The determination of empirical confidence intervals for the location of quantitative trait loci (QTLs) was investigated using simulation. Empirical confidence intervals were calculated using a bootstrap resampling method for a backcross population derived from inbred lines. Sample sizes were either 200 or 500 individuals, and the QTL explained 1, 5, or 10% of the phenotypic variance. The method worked well in that the proportion of empirical confidence intervals that contained the simulated QTL was close to expectation. In general, the confidence intervals were slightly conservatively biased. Correlations between the test statistic and the width of the confidence interval were strongly negative, so that the stronger the evidence for a QTL segregating, the smaller the empirical confidence interval for its location. The size of the average confidence interval depended heavily on the population size and the effect of the QTL. Marker spacing had only a small effect on the average empirical confidence interval. The LOD drop-off method to calculate empirical support intervals gave confidence intervals that generally were too small, in particular if confidence intervals were calculated only for samples above a certain significance threshold. The bootstrap method is easy to implement and is useful in the analysis of experimental data.
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                Author and article information

                Journal
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                2006
                18 July 2006
                : 7
                : 178
                Affiliations
                [1 ]AgResearch, Invermay Agricultural Centre, Private Bag 50034, Mosgiel, New Zealand
                [2 ]AgResearch, Molecular Biology Unit, Department of Biochemistry, University of Otago, Box 56, Dunedin, New Zealand
                [3 ]AgResearch, Wallaceville Animal Research Centre, PO Box 40063, Upper Hutt, New Zealand
                [4 ]AgResearch, Woodlands, Private Bag 90121, Invercargill, New Zealand
                [5 ]Banco de Tumores, Anatomia Patologica, Complejo Hospitalario de Leon, 24008 Leon, Spain
                Article
                1471-2164-7-178
                10.1186/1471-2164-7-178
                1574317
                16846521
                51a05812-4630-4f56-8a6d-8380cc3a6b9b
                Copyright © 2006 Crawford et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 March 2006
                : 18 July 2006
                Categories
                Research Article

                Genetics
                Genetics

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