RESUMEN
AIMS: Most breeds of goat are more susceptible to nematode infection than sheep, and this appears to be a consequence of less effective immune responses. Several papers have considered the effectiveness of eosinophils and immunoglobulin A (IgA) in goats but differences in the induction of responses have not been studied in the same detail. The aim of this study was to look at the induction of eosinophil and IgA responses in Boer goats reared indoors under intensive conditions. METHODS AND RESULTS: The goats were experimentally infected with a low dose of 2400 Haemonchus contortus, Trichostrongylus spp. and Oesophagostomum spp. at a 6:1:1 ratio. Faecal egg counts (FEC), packed cell volume (PCV), IgA activity against third-stage larvae and peripheral eosinophilia were measured twice a week for eight weeks. The infection generated an IgA response but did not significantly increase peripheral eosinophilia in the 25 infected kids compared with the 4 control animals. FEC was not associated with IgA activity or eosinophilia. CONCLUSION: A detailed analysis of IgA and eosinophil responses to deliberate nematode infection in Boer goats showed that there was an increase in nematode-specific IgA activity but no detectable eosinophil response. In addition, there was no association between increased IgA activity or eosinophilia with egg counts and worm burdens. These suggest that IgA and eosinophils do not act to control nematode infection in goats.
Asunto(s)
Eosinofilia/inmunología , Enfermedades de las Cabras/parasitología , Cabras/inmunología , Hemoncosis/veterinaria , Haemonchus/inmunología , Inmunoglobulina A/inmunología , Animales , Anticuerpos Antiprotozoarios/inmunología , Eosinofilia/parasitología , Eosinófilos/inmunología , Heces/parasitología , Femenino , Enfermedades de las Cabras/inmunología , Cabras/parasitología , Hemoncosis/inmunología , Hemoncosis/parasitología , Hematócrito/veterinaria , Recuento de Leucocitos , Masculino , Oesophagostomum/inmunología , Recuento de Huevos de Parásitos/veterinaria , Trichostrongylus/inmunologíaRESUMEN
An epidemiological study of gastrointestinal nematodes was carried out in naturally infected goats in the North West of Algeria. Coprological analyses were performed for 2 years from January 2014 to December 2015.Examination of 1591 goat samples revealed an overall prevalence of parasite eggs in feces of 96%; the values were very similar in both years at 97% in 2014 and 94.96% in 2015. Five types of nematode eggs were identified: strongyle (95.5%), Nematodirus spp. (19.4%), Marshallagia spp. (3.9%), Trichuris spp. (0.6%), and Skrjabinema spp. (2%).Also, fecal cultures showed the presence of Teladorsagia spp. (56%), Trichostrongylus spp. (20%), Chabertia spp. (10%), Haemonchus spp. (9%), and Oesophagostomum spp. (5%).Season, age, type of grazing, and area affected the epidemiology of gastrointestinal nematodes of goats. The season did not influence the prevalence observed in the 2 years, since no significant differences between the four seasons were observed. On the other hand, egg production was highest in winter and spring. The level of infection decreased with the animal's age. There were no significant differences between the prevalence in animals on irrigated and non-irrigated pastures, but there were differences in egg excretion. Additionally, no significant difference was observed between the coastal (Oran) and lowland (Mascara) regions in the prevalence or in average egg excretion.
Asunto(s)
Enfermedades de las Cabras/parasitología , Infecciones por Nematodos/veterinaria , Recuento de Huevos de Parásitos/veterinaria , Argelia/epidemiología , Animales , Heces/parasitología , Enfermedades de las Cabras/epidemiología , Cabras , Nematodos/clasificación , Infecciones por Nematodos/epidemiología , PrevalenciaRESUMEN
Nematode infection is one of the principal diseases suffered by sheep and the class II region of the MHC has been repeatedly associated with differences in susceptibility and resistance to infection. The aim of this study was to examine the association of MHC class II haplotypes in a flock of Texel sheep with faecal egg counts and antibody responsiveness. Two haplotypes carried the DRB1*11:01 allele which has previously been associated with reduced egg counts in Scottish Blackface and Suffolk sheep. One of the two haplotypes was associated with reduced egg counts in the Texel breed, and both haplotypes were associated with reduced IgA activity against an extract from fourth-stage larvae. The reduced IgA activity is probably a consequence of reduced numbers of fourth-stage larvae in sheep carrying the resistance allele. The association of specific MHC alleles with reduced egg counts, reduced worm numbers and decreased IgA activity provides a mechanism for the density-dependent regulation of parasite growth and fecundity.
Asunto(s)
Genes MHC Clase II , Inmunoglobulina A/inmunología , Recuento de Huevos de Parásitos , Enfermedades de las Ovejas/inmunología , Infecciones por Strongylida/veterinaria , Estrongílidos/inmunología , Animales , Heces/parasitología , Haplotipos , Ovinos , Enfermedades de las Ovejas/parasitología , Oveja Doméstica , Infecciones por Strongylida/inmunología , Infecciones por Strongylida/parasitologíaRESUMEN
Understanding the structure of the major histocompatibility complex, especially the number and frequency of alleles, loci and haplotypes, is crucial for efficient investigation of the way in which the MHC influences susceptibility to disease. Nematode infection is one of the most important diseases suffered by sheep, and the class II region has been repeatedly associated with differences in susceptibility and resistance to infection. Texel sheep are widely used in many different countries and are relatively resistant to infection. This study determined the number and frequency of MHC class II genes in a small flock of Texel sheep. There were 18 alleles at DRB1, 9 alleles at DQA1, 13 alleles at DQB1, 8 alleles at DQA2 and 16 alleles at DQB2. Several haplotypes had no detectable gene products at DQA1, DQB1 or DQB2, and these were defined as null alleles. Despite the large numbers of alleles, there were only 21 distinct haplotypes in the population. The relatively small number of observed haplotypes will simplify finding disease associations because common haplotypes provide more statistical power but complicate the discrimination of causative mutations from linked marker loci.
Asunto(s)
Genes MHC Clase II/genética , Antígenos HLA/genética , Haplotipos/genética , Ovinos/genética , Población Blanca/genética , Alelos , Animales , Frecuencia de los Genes , HumanosRESUMEN
We aimed to describe the evolution of resistance to amitraz in Rhipicephalus microplus in the field and to test the association between amitraz resistance and the frequency of a mutation in the ß-adrenergic octopamine receptor gene (RmßAOR). We established six populations of Rhipicephalus microplus ticks in similar paddocks by the admixture of ticks from strains known to be susceptible and resistant to amitraz and synthetic pyrethroids. Each population was managed using one of three acaricide treatment regimes: always amitraz, always spinosad, or rotation between amitraz and spinosad. We used microsatellites to elucidate population structure over time, an SNP in the para-sodium channel gene previously demonstrated to confer resistance to synthetic pyrethroids to quantify changes in resistance to synthetic pyrethroids over time, and a nonsynonymous SNP in the RmßAOR, a gene that we proposed to confer resistance to amitraz, to determine whether selection with amitraz increased the frequency of this mutation. The study showed panmixia of the two strains and that selection of ticks with amitraz increased the frequency of the RmßAOR mutation while increasing the prevalence of amitraz-resistance. We conclude that polymorphisms in the RmßAOR gene are likely to confer resistance to amitraz.
Asunto(s)
Proteínas de Artrópodos , Resistencia a Medicamentos , Insecticidas/farmacología , Mutación , Receptores de Amina Biogénica , Rhipicephalus , Toluidinas/farmacología , Animales , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Bovinos , Combinación de Medicamentos , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/genética , Genes , Macrólidos/farmacología , Polimorfismo de Nucleótido Simple , Receptores de Amina Biogénica/genética , Receptores de Amina Biogénica/metabolismo , Rhipicephalus/genética , Rhipicephalus/metabolismoRESUMEN
BACKGROUND: The genetic architecture of complex traits in farmed animal populations is of interest from a scientific and practical perspective. The use of genetic markers to predict the genetic merit (breeding values) of individuals is commonplace in modern farm animal breeding schemes. Recently, high density SNP arrays have become available for Atlantic salmon, which facilitates genomic prediction and association studies using genome-wide markers and economically important traits. The aims of this study were (i) to use a high density SNP array to investigate the genetic architecture of weight and length in juvenile Atlantic salmon; (ii) to assess the utility of genomic prediction for these traits, including testing different marker densities; (iii) to identify potential candidate genes underpinning variation in early growth. RESULTS: A pedigreed population of farmed Atlantic salmon (n = 622) were measured for weight and length traits at one year of age, and genotyped for 111,908 segregating SNP markers using a high density SNP array. The heritability of both traits was estimated using pedigree and genomic relationship matrices, and was comparable at around 0.5 and 0.6 respectively. The results of the GWA analysis pointed to a polygenic genetic architecture, with no SNPs surpassing the genome-wide significance threshold, and one SNP associated with length at the chromosome-wide level. SNPs surpassing an arbitrary threshold of significance (P < 0.005, ~ top 0.5 % of markers) were aligned to an Atlantic salmon reference transcriptome, identifying 109 SNPs in transcribed regions that were annotated by alignment to human, mouse and zebrafish protein databases. Prediction of breeding values was more accurate when applying genomic (GBLUP) than pedigree (PBLUP) relationship matrices (accuracy ~ 0.7 and 0.58 respectively) and 5,000 SNPs were sufficient for obtaining this accuracy increase over PBLUP in this specific population. CONCLUSIONS: The high density SNP array can effectively capture the additive genetic variation in complex traits. However, the traits of weight and length both appear to be very polygenic with only one SNP surpassing the chromosome-wide threshold. Genomic prediction using the array is effective, leading to an improvement in accuracy compared to pedigree methods, and this improvement can be achieved with only a small subset of the markers in this population. The results have practical relevance for genomic selection in salmon and may also provide insight into variation in the identified genes underpinning body growth and development in salmonid species.
Asunto(s)
Acuicultura , Estudio de Asociación del Genoma Completo , Genómica , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple/genética , Salmo salar/crecimiento & desarrollo , Salmo salar/genética , Animales , Cruzamiento , Marcadores Genéticos/genética , Humanos , Ratones , Transcripción GenéticaRESUMEN
Genes from the Major Histocompatibility Complex class II region are involved in the presentation of antigens. Therefore, they have the key role in regulating the immune response and in the resistance to infections. We investigated the Major Histocompatibility Complex class IIB genes, DRB and DQB, in Churra sheep, one of the most important indigenous breeds of Spain. These genes are among the most polymorphic in the mammalian genome. Furthermore, often different numbers of class IIB genes per haplotype exist, complicating the genotyping and sequencing of these genes. Especially the DQB region is only partially characterized in sheep and the repertoire of DRB and DQB alleles in Churra sheep, an ancient breed, is unknown. Here, we sequenced the class IIB genes for 15 rams that are the pedigree heads of a selection Nucleus herd. In total, we found 12 DRB and 25 DQB alleles. From these, 3 and 15 were new, respectively. Fourteen haplotypes carrying one or two DQB alleles could be deduced and the evolutionary relationship of these was investigated by phylogenetic trees. Based on the sequences of these most common class II alleles, a more efficient genotyping system for larger numbers of Churra sheep will be developed.
Asunto(s)
Genes MHC Clase II/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Oveja Doméstica/genética , Oveja Doméstica/inmunología , Secuencia de Aminoácidos/genética , Animales , Secuencia de Bases , Cadenas beta de HLA-DQ/inmunología , Cadenas HLA-DRB1/inmunología , Haplotipos/genética , Masculino , Repeticiones de Microsatélite/genética , Datos de Secuencia Molecular , Alineación de Secuencia/veterinaria , Análisis de Secuencia de ADN/veterinaria , EspañaRESUMEN
Accurately identifying resistance to gastrointestinal nematode infections requires the ability to identify animals with low and high intensities of infection. The pathogenic effects of nematodes depend upon both the length and number of worms, neither of which can be measured in live animals. Indices that predict these quantities are urgently needed. Monthly fecal egg counts, bodyweights, IgA concentrations and pepsinogen concentrations were measured on Scottish Blackface sheep naturally infected with a mixture of nematodes, predominantly Teladorsagia circumcincta. Worm number and average worm length were available on over 500 necropsied lambs. We derived predictive indices for worm length and number using linear combinations of traits measured in live animals. The correlations between the prediction values and the observed values were 0.55 for worm length and 0.51 for worm number. These indices can be used to identify the most resistance and susceptible lambs.
Asunto(s)
Nematodos/anatomía & histología , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/parasitología , Animales , Peso Corporal , Heces/parasitología , Inmunoglobulina A/sangre , Análisis Multivariante , Nematodos/fisiología , Infecciones por Nematodos/parasitología , Recuento de Huevos de Parásitos , Pepsinógeno A/sangre , OvinosRESUMEN
Immunoglobulin A (IgA) activity has been associated with reduced growth and fecundity of Teladorsagia circumcincta. IgA is active at the site of infection in the abomasal mucus. However, while IgA activity in abomasal mucus is not easily measured in live animals without invasive methods, IgA activity can be readily detected in the plasma, making it a potentially valuable tool in diagnosis and control. We used a Bayesian statistical analysis to quantify the relationship between mucosal and plasma IgA in sheep deliberately infected with T. circumcincta. The transfer of IgA depends on mucosal IgA activity as well as its interaction with worm number and size; together these account for over 80% of the variation in plasma IgA activity. By quantifying the impact of mucosal IgA and worm number and size on plasma IgA, we provide a tool that can allow more meaningful interpretation of plasma IgA measurements and aid the development of efficient control programmes.
Asunto(s)
Inmunoglobulina A , Moco/química , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/parasitología , Animales , Modelos Biológicos , Infecciones por Nematodos/sangre , Infecciones por Nematodos/diagnóstico , Infecciones por Nematodos/inmunología , Infecciones por Nematodos/parasitología , Ovinos , Enfermedades de las Ovejas/sangre , Enfermedades de las Ovejas/inmunologíaRESUMEN
Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder of older horses. Immune dysfunction in horses with PPID could increase susceptibility to infectious diseases, including strongyle infections; however, few data are available. The aim of this study was to determine if horses with PPID had increased strongyle faecal egg counts (FEC) compared with control horses, over a fourteen-week period in Victoria, Australia. Clinical signs and plasma adrenocorticotropic hormone (ACTH) concentrations were used to categorise horses into PPID (n=14) or control (n=31) groups. Faecal samples were collected for FEC determination prior to anthelmintic treatment, and fortnightly post-treatment for each horse. Generalised linear mixed modelling, using a gamma distribution, was used to compare differences between groups in the repeated measures study. The confounding variable of age was controlled for as a fixed effect. Following anthelmintic treatment, mean FEC was greater for the PPID group compared to the control group on day 56 (405 ± 756 eggs per gram [EPG] vs 40 ± 85 EPG, p=0.05) and day 70 (753 ±1598 EPG vs 82 ±141 EPG, p=0.04). There were no differences in mean FEC between groups on days 84 and 98. Cumulative FEC (day 14 to day 98) was significantly greater for the PPID horses than control horses (2118 ± 4016 EPG vs 798 ± 768 EPG, p<0.0001). Group egg reappearance period was shorter for PPID horses (day 56 post-anthelmintic treatment) compared to control horses (day 70) and 30% of the PPID horses reached a FEC threshold of >200 EPG on day 42, compared to 0% of control horses (p=0.02). These results suggest that the rate of a re-established patent infection between groups could be different due to a comprised immune response in PPID horses or differences in the host-parasite relationship regarding encysted stage larvae. However, despite differences between groups, some horses with PPID consistently had no detectable or low FEC (<200 EPG) during the study period. These findings highlight the importance of individual FEC monitoring to determine if anthelmintic treatment is required, in line with sustainable parasite management practices.
Asunto(s)
Antihelmínticos , Heces , Recuento de Huevos de Parásitos , Enfermedades de la Hipófisis , Adenohipófisis Porción Intermedia , Infecciones Equinas por Strongyloidea , Animales , Caballos , Recuento de Huevos de Parásitos/veterinaria , Heces/parasitología , Enfermedades de la Hipófisis/veterinaria , Enfermedades de la Hipófisis/parasitología , Antihelmínticos/uso terapéutico , Femenino , Infecciones Equinas por Strongyloidea/parasitología , Infecciones Equinas por Strongyloidea/tratamiento farmacológico , Masculino , Enfermedades de los Caballos/parasitología , Enfermedades de los Caballos/tratamiento farmacológico , Hormona Adrenocorticotrópica/sangre , VictoriaRESUMEN
The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic molecules involved in antigen presentation. Six classical class I genes have been described, but assigning sequences to these genes has proved problematic. We propose a refinement of the existing nomenclature, which currently names the 97 known classical class I sequences in a single series. Phylogenetic analysis of the 3' portion of the coding region allows segregation of these into six groups; thus, we have prefixed existing names with the appropriate number. Although it is clear that some of these groups correspond to discrete genes, it is currently not possible to state definitively that all do. However, the main groupings are consistent, and in conjunction with other evidence, we feel it is now appropriate to rename the sequences accordingly. Segregation of sequences into groups in this way will facilitate ongoing research and future use of the cattle MHC section of the Immuno Polymorphism Database.
Asunto(s)
Bovinos/inmunología , Genes MHC Clase I , Complejo Mayor de Histocompatibilidad , Terminología como Asunto , Animales , FilogeniaRESUMEN
Mast cell degranulation is the major mechanism influencing establishment and survival of the abomasal nematode Teladorsagia circumcincta and probably many other gastrointestinal nematodes. Host galectins-3 and -9 have been shown to bind IgE and positively and negatively influence mast cell degranulation. As incoming nematodes produce large amounts of galectin, we hypothesised that nematode galectin competes with host galectin and inhibits mast cell degranulation. ELISA was used to show that nematode galectin reduced total IgE activity. Galectin also reduced the binding of sheep IgE to the surface of a mast cell line and decreased the release of LCT-4 and Beta hexosaminidase but not MMP-9. These results indicate that nematode galectin influences mast cell degranulation and identify a potential immunomodulatory mechanism used by nematodes to enhance their establishment and survival.
Asunto(s)
Mastocitos , Nematodos , Ovinos , Animales , Galectinas/metabolismo , beta-N-Acetilhexosaminidasas , Inmunoglobulina ERESUMEN
Eosinophils play a key role in defence against gastrointestinal nematodes. There is considerable variation among animals in the intensity of eosinophilia following nematode infection. However, the statistical distribution of eosinophils among animals has still to be determined. A better description of the variation among animals could provide biological insight and determine the most appropriate way to analyse the effect of eosinophils. We estimated blood eosinophil numbers in a flock of Scottish Blackface sheep that were naturally exposed to mixed, predominantly Teladorsagia circumcincta infection. Three of the four eosinophil counts were better described by a gamma distribution than by a lognormal distribution. The scale and shape parameters of the gamma distribution varied over time. Eosinophil counts differed among animals kept on separate fields before weaning and between singletons and twins but were not significantly different between years and genders. Eosinophil counts also differed among offspring from different sires and dams. The parameters of the gamma distribution were used to enable a power analysis. Large numbers of animals were required to reliably detect even large differences between two groups. These results indicate that methods appropriate for gamma distributions, such as generalized linear mixed models, will provide more reliable inferences than traditional methods of analysis and experimental design.
Asunto(s)
Eosinofilia , Nematodos , Infecciones por Nematodos , Enfermedades de las Ovejas , Animales , Eosinofilia/veterinaria , Heces , Femenino , Masculino , Infecciones por Nematodos/veterinaria , Recuento de Huevos de Parásitos/veterinaria , Escocia/epidemiología , Ovinos , Enfermedades de las Ovejas/epidemiologíaRESUMEN
The protein tyrosine phosphatase receptor type-C (PTPRC) gene encodes the common leukocyte antigen (CD45) receptor. CD45 affects cell adhesion, migration, cytokine signalling, cell development, and activation state. Four families of the gene have been identified in cattle: a taurine group (Family 1), two indicine groups (Families 2 and 4) and an African "taurindicine" group (Family 3). Host resistance in cattle to infestation with ticks is moderately heritable and primarily manifests as prevention of attachment and feeding by larvae. This study was conducted to describe the effects of PTPRC genotype on immune-response phenotypes in cattle that display a variable immune responsiveness to ticks. Thirty tick-naïve Santa-Gertrudis cattle (a stabilized composite of 5/8 taurine and 3/8 indicine) were artificially infested with ticks weekly for 13 weeks and ranked according to their tick counts. Blood samples were taken from control and tick-challenged cattle immediately before, then at 21 d after infestation and each subsequent week for 9 weeks. Assays included erythrocyte profiles, white blood cell counts, the percentage of cellular subsets comprising the peripheral blood mononuclear cell (PBMC) population, and the ability of PBMC to recognize and proliferate in response to stimulation with tick antigens in vitro. The cattle were PTPRC genotyped using a RFLP assay that differentiated Family 1 and 3 together (220 bp), from Family 2 (462 bp), and from Family 4 (486 bp). The PTPRC allele frequencies were Family 1/3 = 0.34; Family 2 = 0.47; Family 4 = 0.19. There was no significant association between PTPRC genotype and tick count. Each copy of the Family 1/3 allele significantly decreased total leucocyte count (WCC) and CD8+ cells. Increasing dosage of Family 2 alleles significantly increased red blood cell count (RCC), haematocrit (PCV), and haemoglobin (Hb) concentration in blood. Increasing dosage of the Family 4 allele was associated with increased WCC, reduced RCC, reduced PCV and reduced Hb. Homozygote Family 1/3 animals had consistently lower IgG1 in response to tick Ag than homozygote Family 2 animals. The PTPRC genotype influences the bovine immune response to ticks but was not associated with the observed variation in resistance to tick infestation in this study.
Asunto(s)
Alelos , Enfermedades de los Bovinos/inmunología , Antígenos Comunes de Leucocito/genética , Infestaciones por Garrapatas/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/sangre , Recuento de Eritrocitos , Humanos , Inmunoglobulina G/sangre , Recuento de Leucocitos , Infestaciones por Garrapatas/sangre , Infestaciones por Garrapatas/inmunologíaRESUMEN
BACKGROUND: One of the major obstacles to the exploitation of genetic variation in human medicine, veterinary medicine, and animal breeding is the difficulty in defining haplotypes in unrelated individuals. RESULTS: We have developed a Multiplex Double Amplification Refractory Mutation System combined with Solid Phase PCR on Fluorescently labelled beads. The process is inherently amenable to automation. It provides a high degree of internal Quality Control, as each PCR product is represented in duplicate on the bead array, and each SNP is tested against multiple partners. This technique can resolve very complex genotypes into their constituent haplotypes; it defined all the alleles at 60 SNP in exon 2 of the ovine DRB1 MHC locus in a sample of 109 rams. These 60 SNP formed 33 DRB1 exon 2 alleles; two of which had not been previously identified; although both of them have been independently confirmed. CONCLUSION: This technique has the same resolution as allele specific sequencing. Sequencing has the advantage of identifying novel polymorphic sites but where all SNP sites have been identified this novel procedure can resolve all alleles and haplotypes and identify novel combinations of polymorphisms. This method is similar in price to direct sequencing and provides a low cost system for direct haplotyping of extended DNA sequences.
Asunto(s)
Análisis Mutacional de ADN/métodos , ADN/análisis , Genoma , Haplotipos , Reacción en Cadena de la Polimerasa/métodos , Alelos , Animales , Secuencia de Bases , ADN/genética , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Ovinos/genéticaRESUMEN
This review addresses the research landscape regarding vaccines against scour worms, particularly Trichostrongylus spp. and Teladorsagia circumcincta. The inability of past research to deliver scour-worm vaccines with reliable and reproducible efficacy has been due in part to gaps in knowledge concerning: (i) host-parasite interactions leading to development of type-2 immunity, (ii) definition of an optimal suite of parasite antigens, and (iii) rational formulation and administration to induce protective immunity against gastrointestinal nematodes (GIN) at the site of infestation. Recent 'omics' developments enable more systematic analyses. GIN genomes are reaching completion, facilitating "reverse vaccinology" approaches that have been used successfully for the Rhipicephalus australis vaccine for cattle tick, while methods for gene silencing and editing in GIN enable identification and validation of potential vaccine antigens. We envisage that any efficacious scour worm vaccine(s) would be adopted similarly to "Barbervax™" within integrated parasite management schemes. Vaccines would therefore effectively parallel the use of resistant animals, and reduce the frequency of drenching and pasture contamination. These aspects of integration, efficacy and operation require updated models and validation in the field. The conclusion of this review outlines an approach to facilitate an integrated research program.
Asunto(s)
Ostertagiasis/veterinaria , Enfermedades Parasitarias en Animales/prevención & control , Rumiantes/parasitología , Tricostrongiliasis/veterinaria , Vacunas , Animales , Ostertagia , Ostertagiasis/prevención & control , Tricostrongiliasis/prevención & control , TrichostrongylusRESUMEN
BACKGROUND: Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes can modulate susceptibility to the parasite. In this study, we used quantitative trait locus (QTL) analysis to test the effect of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6, respectively. RESULTS: Significant QTL effects were detected on both LG 6 and LG 15 in sire-based analysis but the QTL regions remained unresolved due to a lack of recombination between markers. In dam-based analysis, a significant QTL was identified on LG 6, which accounted for 12.9% of within-family variance in lice abundance. However, the QTL was located at the opposite end of DAA, with no significant overlap with the MHC class II region. Interestingly, QTL modelling also revealed evidence of sex-linked differences in lice abundance, indicating that males and females may have different susceptibility to infection. CONCLUSION: Overall, QTL analysis provided relatively weak support for a proximal effect of classical MHC regions on lice abundance, which can partly be explained by linkage to other genes controlling susceptibility to L. salmonis on the same chromosome.
Asunto(s)
Copépodos/fisiología , Complejo Mayor de Histocompatibilidad/genética , Sitios de Carácter Cuantitativo/genética , Salmo salar/genética , Salmo salar/parasitología , Animales , Peso Corporal/genética , Mapeo Cromosómico , Femenino , Enfermedades de los Peces/genética , Enfermedades de los Peces/parasitología , Predisposición Genética a la Enfermedad , Interacciones Huésped-Parásitos , Masculino , Modelos GenéticosRESUMEN
The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. However, both theoretical results and simulation models have shown that overdominance in its classical form cannot maintain large numbers of alleles unless all alleles confer unrealistically similar levels of fitness. There is increasing evidence that heterozygotes containing genetically divergent alleles allow for broader antigen presentation to immune cells, providing a selective mechanism for MHC polymorphism. By framing competing models of overdominance within a general framework, we show that a model based on Divergent Allele Advantage (DAA) provides a superior mechanism for maintaining alleles with a wide range of intrinsic merits, as intrinsically less-fit MHC alleles that are more divergent can survive under DAA. Specifically, our results demonstrate that a quantitative mechanism built from the DAA hypothesis is able to maintain polymorphism in the MHC. Applying such a model to both livestock breeding and conservation could provide a better way of identifying superior heterozygotes, and quantifying the advantages of genetic diversity at the MHC.
Asunto(s)
Alelos , Variación Genética , Complejo Mayor de Histocompatibilidad/genética , Polimorfismo Genético , Selección Genética , Animales , Heterocigoto , Modelos GenéticosRESUMEN
Lambs with the Major Histocompatibility Complex DRB1*1101 allele have been shown to produce fewer nematode eggs following natural and deliberate infection. These sheep also possess fewer adult Teladorsagia circumcincta than sheep with alternative alleles at the DRB1 locus. However, it is unclear if this allele is responsible for the reduced egg counts or merely acts as a marker for a linked gene. This study defined the MHC haplotypes in a population of naturally infected Scottish Blackface sheep by PCR amplification and sequencing, and examined the associations between MHC haplotypes and faecal egg counts by generalised linear mixed modelling. The DRB1*1101 allele occurred predominately on one haplotype and a comparison of haplotypes indicated that the causal mutation or mutations occurred in or around this locus. Additional comparisons with another resistant haplotype indicated that mutations in or around the DQB2*GU191460 allele were also responsible for resistance to nematode infections. Further analyses identified six amino acid substitutions in the antigen binding site of DRB1*1101 that were significantly associated with reductions in the numbers of adult T. circumcincta.
Asunto(s)
Aminoácidos/análisis , Genes MHC Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/química , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/inmunología , Enfermedades de las Ovejas/parasitología , Aminoácidos/inmunología , Animales , Estudios de Cohortes , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Heces/parasitología , Femenino , Haplotipos , Modelos Lineales , Masculino , Infecciones por Nematodos/inmunología , Infecciones por Nematodos/parasitología , Recuento de Huevos de Parásitos/veterinaria , Polimorfismo Genético , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Escocia , Ovinos , Trichostrongyloidea/inmunología , Tricostrongiloidiasis/inmunología , Tricostrongiloidiasis/parasitología , Tricostrongiloidiasis/veterinariaRESUMEN
Gastrointestinal nematodes (GIN) are a major constraint for small ruminant production. Due to the rise of anthelmintic resistance throughout the world, alternative control strategies are needed. The development of GIN resistance breeding programs is a promising strategy. However, a better understanding of the mechanisms underlying genetic resistance might lead to more effective breeding programmes. In this study, we compare transcriptome profiling of abomasal mucosa and lymph node tissues from non-infected, resistant and susceptible infected Creole goats using RNA-sequencing. A total of 24 kids, 12 susceptible and 12 GIN resistant based on the estimated breeding value, were infected twice with 10,000 L3 Haemonchus contortus. Physiological and parasitological parameters were monitored during infection. Seven weeks after the second infection, extreme kids (n = 6 resistant and 6 susceptible), chosen on the basis of the fecal egg counts (FEC), and 3 uninfected control animals were slaughtered. Susceptible kids had significantly higher FEC compared with resistant kids during the second infection with no differences in worm burden, male and female worm count or establishment rate. A higher number of differentially expressed genes (DEG) were identified in infected compared with non-infected animals in both abomasal mucosa (792 DEG) and lymph nodes (1726 DEG). There were fewer DEG in resistant versus susceptible groups (342 and 450 DEG, in abomasal mucosa and lymph nodes respectively). 'Cell cycle' and 'cell death and survival' were the main identified networks in mucosal tissue when comparing infected versus non-infected kids. Antigen processing and presentation of peptide antigen via major histocompatibility complex class I were in the top biological functions for the DEG identified in lymph nodes. The TGFß1 gene was one of the top 5 upstream DEG in mucosal tissue. Our results are one of the fist investigating differences in the expression profile induced by GIN infection in goats.