Stephen Bishop

Costs of the major endemic diseases of sheep in Great Britain and the potential benefits of reduction in disease impact

The costs of three major endemic sheep diseases in Great Britain, gastro-intestinal (GI) parasites, footrot and scab, were estimated and compared with costs for other diseases from another study. Disease costs include lost performance, preventive measures and treatment of affected animals. The most costly disease, of those studied, for the British sheep industry is infestation with GI parasites, with estimated annual costs of £84 million. Annual costs for the other two diseases are £24 million for footrot and £8 million for sheep scab. This compares with literature estimates of £20 million for Chlamydial abortions and £12 million for toxoplasmosis. For sheep scab most costs are for preventive measures, therefore, short of eradication, a reduction in incidence will have a limited effect on costs. For GI parasites, costs are linearly related to the severity of the infestation and a reduction of the disease will have a proportional effect on the costs to the industry. For footrot about half the costs are for preventive measures, the other half is for lost production and treatment. A reduction in the incidence of footrot has a proportional effect on the £10 million associated with loss of production and treatment of infected animals. It is concluded that gastro-intestinal parasites and footrot are two sheep diseases in Britain for which a reduction of severity or incidence will have a large impact on costs of production.

Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta

Following infection with Ostertagia circumcincta there was considerable variation in worm burdens, worm size and number of inhibited larvae even among sheep matched for age, sex, breed, farm of origin and history of parasite exposure. There was also substantial variation among sheep in the concentration of mast cells, globule leucocytes, eosinophils, IgA‐positive plasma cells and parasite‐specific IgA in the abomasal mucosa. With the exception of faecal egg counts over time, the parasitological and immunological traits were all continually distributed among animals and sheep did not fall into discrete high and low‐responder categories. The responses were correlated. Sheep with more mast cells also had more globule leucocytes, more eosinophils, more IgA plasma cells and greater amounts of parasite‐specific IgA in the abomasal mucosa. Female worm length was strongly and positively correlated with the number of eggs in utero. Faecal egg counts were associated with variation in worm number and with variation in the number of eggs in utero. The worm burden was negatively correlated with the number of globule leucocytes in the abomasal mucosa, suggesting that worm numbers are regulated by immediate hypersensitivity reactions. Decreased female worm length was associated with an increased local IgA response to fourth stage larvae. The number of inhibited larvae was positively associated with the size of the local IgA response and positively associated with the size of the worm burden. The results suggest that variation among mature sheep in faecal egg counts is due, at least in part, to variation in local IgA responses which regulate worm fecundity and to variation in local immediate hypersensitivity reactions which regulate worm burdens.

Genetic variation in residual feed intake and its association with other production traits in British Hereford cattle

Abstract Variation in residual feed intake, that is, variation in feed intake in relation to liveweight (LW) and growth rate, was investigated using data from 540 progeny of 154 British Hereford sires, collected over ten 200-day postweaning performance tests conducted between 1979 and 1988. Residual feed intake (RFI Reg ) was calculated for each test as the difference between actual feed and expected feed intake predicted from a multiple regression of feed intake on metabolic mid-test LW and average daily gain (ADG). RFI Reg was heritable (0.16, S.E. 0.08) and phenotypically and genetically independent of size and growth rate. RFI Reg had favourable phenotypic and genetic correlations with feed conversion ratio (FCR) and estimated maintenance energy expenditure. It was negatively correlated with estimated lean content of the carcase (LEAN) and appeared to be genetically independent of mature cow LW (COWWT). RFI Reg over the performance test was not affected by differences in pre-test rearing treatments, in contrast to start-of-test LW and end-of-test LW, and in some years, ADG and FCR. Selection against RFI has the potential to increase the efficiency of beef production by reducing feed intake without changing the growth rate of the young animal, or increasing mature cow size.

Genetic parameters for faecal egg count following mixed, natural, predominantly Ostertagia circumcincta infection and relationships with live weight in young lambs

Faecal egg counts and live weights were measured on approximately 200 predominantly twin-born Scottish Blackface lambs each year for 3 years, from 1 to 6 1lonths of age. Measurements lvere made at 4-tieek mt/:ltlals following anthelmintic treatment. Heritability estimates (with s.e.s) of log transformed faecal egg count at each age were 0.01,0.00,0.12 (0.10), 0.14 (0.12), 0.15 (0.07) ard 0.22 (0.13), for ages 1 to 6 months respectively. Therefore, genetic variation exists for acquired but apparentl~ not for innate resistance to infection. Maternal common environmental effects (with s.e.s) were 0.36 (0.11), 0.2b (0.05), 0.27 (0.09),0.06 (0.08), 0.15 (0.09) and 0.16 (0.08), for ages 1 to 6 months respectively. Genetic correlatiqns between faecal egg counts in Iambs older than 3 mpnths uere not significantly less than 1.0, indicating that faecal egg counts at different ages are expressions of the same trait. Phenotypic correlations between faecal egg colfnts were generally positive but small. Measurement ,error contributed one-third of the observed variation for indrvidual egg counts. The heritability of mean faecal egg count from.3 to 6 months was 0:33 (s.e. 0.15), .indicatin~ ~hat selection decisions can be ma~e mo~e accurately using multIple egg counts per anImal. PhenotypIc correlatIons between faecal egg counts and live weIght were generally negative but close to zero. However, genetic correlati~ns between faecal egg counts and live weight in lambs older than 3 months were close to -1.0, indicating that r~sistance to gastrointestinal parasites may be an important genetic determinant of growth rate in this environment.

Quantitative trait loci associated with parasitic infection in Scottish blackface sheep

This study aimed to identify quantitative trait loci associated with endoparasitic infection in Scottish Blackface sheep. Data were collected from 789 animals over a 3-year period. All of the animals were continually exposed to a mixed nematode infection by grazing. Faecal samples were collected in August, September and October each year at ca. 16, 20 and 24 weeks of age; Nematodirus spp. eggs were counted separately from the other species of nematodes. Blood samples were collected in October from which immunoglobulin A (IgA) activity was measured and DNA was extracted for genotyping. In total, 139 Microsatellite markers were genotyped across eight chromosomal regions (chromosomes 1, 2, 3, 5, 14, 18, 20 and 21) in the sires and progeny were genotyped for the markers that were polymorphic in their sire. Evidence was found for quantitative trait loci (QTL) on chromosomes 2, 3, 14 and 20. QTL associated with specific IgA activity were identified in chromosomes 3 and 20, in regions close to IFNG (chromosome 3) and the MHC (chromosome 20). QTL associated with Nematodirus FEC were identified on chromosomes 2, 3 and 14. Lastly, QTL associated with non-Nematodirus Strongyle FEC were identified on chromosomes 3 and 20. This study has shown that some aspects of host resistance to gastrointestinal parasites are under strong genetic control, therefore these QTL could be utilised in a marker-assisted selection scheme to increase host resistance to gastrointestinal parasites.

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar)

BackgroundDense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array.ResultsSNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex.ConclusionsThis manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection.

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

The control of fecundity is critical in determining mammalian offspring survival. It is regulated principally by the ovulation rate, so that primates and large farm species commonly have a single offspring. Previously, several mutations have been identified in sheep which increase the naturally low ovulation rate; although in some cases homozygous ewes are infertile. In the present study we present a detailed characterization of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a nonconservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development. Genotyping all animals for which reproductive records were available confirmed this mutation to be associated with increased fecundity in heterozygous ewes and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilization of these animals to enhance sheep production.

Ewe–lamb bonding behaviours at birth are affected by maternal undernutrition in pregnancy

Maternal undernutrition in pregnancy results in low birth-weights and impaired postnatal survival in sheep. Largely anecdotal evidence suggests that the expression of appropriate maternal and neonate behaviours may also be disrupted by undernutrition. In the present study, we investigated the effect of a moderate (35 %) reduction in ewe nutritional intake in pregnancy on the expression of ewe-lamb bonding behaviours in primiparous Scottish Blackface ewes. Low-intake (L) ewes had significantly higher plasma progesterone than high-intake (H) ewes from mid-gestation onwards (e.g. plasma progesterone at 20 weeks (ng/ml): H 15.72, L 22.38, sed 1.80, P<0.001), and a lower oestradiol: progesterone value than H ewes at delivery (H 0.46, L 0.35, sed 0.05, P<0.05). Lamb birth-weight was reduced in the L lambs compared with H lambs (mean body weight (kg): H 3.31, L 3.00, sed 0.14, P<0.05), but the incidence of malpresentation at delivery was greater in L lambs. L ewes spent significantly less time licking their lambs than H ewes after delivery (time grooming in 2 h after birth (%): H 56.12, L 48.17, sed 2.639, P<0.01) and were more aggressive towards the lambs. Lamb behaviours were not directly affected by maternal nutritional treatment, but lamb birth-weight had a significant effect on neonatal developmental progress. Low-birth-weight lambs were slower than heavier lambs to stand and sucked less frequently. In tests of maternal attachment to the lamb, H ewes received higher scores than L ewes at both 24 h after birth (ewes receiving high scores (%): H 41.3, L 21.4, P<0.05) and at 3 d postnatal. We conclude that even a moderate level of undernutrition impairs the attachment between ewes and lambs by affecting maternal behaviours expressed at birth. In addition, the results suggest that levels of nutrition resulting in a decrease in birth weight will affect neonatal lamb behavioural progress.

Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD sequencing

BackgroundGenetic linkage maps are useful tools for mapping quantitative trait loci (QTL) influencing variation in traits of interest in a population. Genotyping-by-sequencing approaches such as Restriction-site Associated DNA sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide SNP markers suitable for the development of dense SNP linkage maps, including in non-model organisms such as Atlantic salmon (Salmo salar). This paper describes the development and characterisation of a high density SNP linkage map based on SbfI RAD-Seq SNP markers from two Atlantic salmon reference families.ResultsApproximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers from known genomic locations as anchors. Linkage maps were then constructed for the four mapping parents separately. Overall map lengths were comparable between male and female parents, but the distribution of the SNPs showed sex-specific patterns with a greater degree of clustering of sire-segregating SNPs to single chromosome regions. The maps were integrated with the Atlantic salmon draft reference genome contigs, allowing the unique assignment of ~4,000 contigs to a linkage group. 112 genome contigs mapped to two or more linkage groups, highlighting regions of putative homeology within the salmon genome. A comparative genomics analysis with the stickleback reference genome identified putative genes closely linked to approximately half of the ordered SNPs and demonstrated blocks of orthology between the Atlantic salmon and stickleback genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high-throughput genotyping assay, with a correspondence of 97% between the two assays.ConclusionsThis Atlantic salmon RAD-Seq linkage map is a resource for salmonid genomics research as genotyping-by-sequencing becomes increasingly common. This is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps and the draft reference genome, as well as the identification of putative genes proximal to the SNPs. Differences in the distribution of recombination events between the sexes is evident, and regions of homeology have been identified which are reflective of the recent salmonid whole genome duplication.

On the Genetic Interpretation of Disease Data

Background The understanding of host genetic variation in disease resistance increasingly requires the use of field data to obtain sufficient numbers of phenotypes. We introduce concepts necessary for a genetic interpretation of field disease data, for diseases caused by microparasites such as bacteria or viruses. Our focus is on variance component estimation and we introduce epidemiological concepts to quantitative genetics. Methodology/Principal Findings We have derived simple deterministic formulae to predict the impacts of incomplete exposure to infection, or imperfect diagnostic test sensitivity and specificity on heritabilities for disease resistance. We show that these factors all reduce the estimable heritabilities. The impacts of incomplete exposure depend on disease prevalence but are relatively linear with the exposure probability. For prevalences less than 0.5, imperfect diagnostic test sensitivity results in a small underestimation of heritability, whereas imperfect specificity leads to a much greater underestimation, with the impact increasing as prevalence declines. These impacts are reversed for prevalences greater than 0.5. Incomplete data recording in which infected or diseased individuals are not observed, e.g. data recording for too short a period, has impacts analogous to imperfect sensitivity. Conclusions/Significance These results help to explain the often low disease resistance heritabilities observed under field conditions. They also demonstrate that incomplete exposure to infection, or suboptimal diagnoses, are not fatal flaws for demonstrating host genetic differences in resistance, they merely reduce the power of datasets. Lastly, they provide a tool for inferring the true extent of genetic variation in disease resistance given knowledge of the disease biology.