RESUMEN
Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.
Asunto(s)
Bovinos/genética , Resistencia a la Enfermedad/genética , Genética de Población , Tuberculosis Bovina/genética , Animales , Bovinos/microbiología , Industria Lechera , Estudio de Asociación del Genoma Completo/veterinaria , Genotipo , Heterocigoto , Irlanda , Modelos Genéticos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. RESULTS: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. CONCLUSIONS: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology.
Asunto(s)
Mapeo Cromosómico , Industria Lechera , Variación Genética , Mycobacterium bovis/fisiología , Tuberculosis Osteoarticular/genética , Animales , Bovinos , Cromosomas de los Mamíferos/genética , Femenino , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
Genetic evaluations for resistance to bovine tuberculosis (bTB) were calculated based on British national data including individual animal tuberculin skin test results, postmortem examination (presence of bTB lesions and bacteriological culture for Mycobacterium bovis), animal movement and location information, production history, and pedigree records. Holstein cows with identified sires in herds with bTB breakdowns (new herd incidents) occurring between the years 2000 and 2014 were considered. In the first instance, cows with a positive reaction to the skin test and a positive postmortem examination were defined as infected. Values of 0 and 1 were assigned to healthy and infected animal records, respectively. Data were analyzed with mixed models. Linear and logit function heritability estimates were 0.092 and 0.172, respectively. In subsequent analyses, breakdowns were split into 2-mo intervals to better model time of exposure and infection in the contemporary group. Intervals with at least one infected individual were retained and multiple intervals within the same breakdown were included. Healthy animal records were assigned values of 0, and infected records a value of 1 in the interval of infection and values reflecting a diminishing probability of infection in the preceding intervals. Heritability and repeatability estimates were 0.115 and 0.699, respectively. Reliabilities and across time stability of the genetic evaluation were improved with the interval model. Subsequently, 2 more definitions of "infected" were analyzed with the interval model: (1) all positive skin test reactors regardless of postmortem examination, and (2) all positive skin test reactors plus nonreactors with positive postmortem examination. Estimated heritability was 0.085 and 0.089, respectively; corresponding repeatability estimates were 0.701 and 0.697. Genetic evaluation reliabilities and across time stability did not change. Correlations of genetic evaluations for bTB with other traits in the current breeding goal were mostly not different from zero. Correlation with the UK Profitable Lifetime Index was moderate, significant, and favorable. Results demonstrated the feasibility of a national genetic evaluation for bTB resistance. Selection for enhanced resistance will have a positive effect on profitability and no antagonistic effects on current breeding goal traits. Official genetic evaluations are now based on the interval model and the last bTB trait definition.
Asunto(s)
Mycobacterium bovis , Tuberculosis Bovina , Animales , Cruzamiento , Bovinos , Femenino , Linaje , FenotipoRESUMEN
In reproducing ewes, a periparturient breakdown of immunity is often observed to result in increased fecal egg excretion, making them the main source of infection for their immunologically naive lambs. In this study, we expanded a simulation model previously developed for growing lambs to explore the impact of the genotype (performance and resistance traits) and host nutrition on the performance and parasitism of both growing lambs and reproducing ewes naturally infected with Teladorsagia circumcincta. Our model accounted for nutrient-demanding phases, such as gestation and lactation, and included a supplementary module to manage the age structure of the ewe flock. The model was validated by comparison with published data. Because model parameters were unknown or poorly estimated, detailed sensitivity analysis of the model was performed for the sheep mortality and the level of infection, following a preliminary screening step. The parameters with the greatest effect on parasite-related outputs were those driving animal growth and milk yield. Our model enables different parasite-control strategies (host nutrition, breeding for resistance and anthelmintic treatments) to be assessed on the long term in a sheep flock. To optimize in silico exploration, the parameters highlighted by the sensitivity analysis should be refined with real data.
Asunto(s)
Interacciones Huésped-Parásitos , Parasitosis Intestinales/veterinaria , Enfermedades de las Ovejas/parasitología , Trichostrongyloidea/aislamiento & purificación , Tricostrongiloidiasis/veterinaria , Animales , Antihelmínticos/uso terapéutico , Genotipo , Parasitosis Intestinales/parasitología , Lactancia , Reproducción , Ovinos , Trichostrongyloidea/clasificación , Trichostrongyloidea/genética , Tricostrongiloidiasis/parasitologíaRESUMEN
Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large negative economic and animal welfare impact on Atlantic salmon aquaculture. Evidence for genetic variation in host resistance to this disease has been reported, suggesting that selective breeding may potentially form an important component of disease control. The aim of this study was to explore the genetic architecture of resistance to PD, using survival data collected from two unrelated populations of Atlantic salmon; one challenged with SAV as fry in freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP 2). Analyses of the binary survival data revealed a moderate-to-high heritability for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP 2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide polymorphism markers, and six putative resistance quantitative trait loci (QTL) were identified. One of these QTL was mapped to the same location on chromosome 3 in both populations, reaching chromosome-wide significance in both the sire- and dam-based analyses in POP 1, and genome-wide significance in a combined analysis in POP 2. This independently verified QTL explains a significant proportion of host genetic variation in resistance to PD in both populations, suggesting a common underlying mechanism for genetic resistance across lifecycle stages. Markers associated with this QTL are being incorporated into selective breeding programs to improve PD resistance.
Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de los Peces/genética , Enfermedades Pancreáticas/veterinaria , Sitios de Carácter Cuantitativo , Salmo salar/genética , Alphavirus , Animales , Mapeo Cromosómico , Femenino , Enfermedades de los Peces/virología , Genética de Población , Genotipo , Patrón de Herencia , Masculino , Modelos Genéticos , Enfermedades Pancreáticas/genética , Enfermedades Pancreáticas/virología , Polimorfismo de Nucleótido Simple , Salmo salar/virologíaRESUMEN
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10(-7)) and myosin IIIB (MYO3B; P=5.4 × 10(-6)). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.
Asunto(s)
Resistencia a la Enfermedad/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/veterinaria , Tuberculosis Bovina/genética , Animales , Bovinos , Mapeo Cromosómico , Cromosomas de los Mamíferos/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Interacciones Huésped-Patógeno/genética , Modelos Lineales , Desequilibrio de Ligamiento , Modelos Logísticos , Mycobacterium bovis/fisiología , Fenotipo , Polimorfismo de Nucleótido Simple , Tuberculosis Bovina/microbiologíaRESUMEN
Gastrointestinal nematode infections are one of the main health/economic issues in sheep industries, worldwide. Indicator traits for resistance such as faecal egg count (FEC) are commonly used in genomic studies; however, published results are inconsistent among breeds. Meta (or joint)-analysis is a tool for aggregating information from multiple independent studies. The aim of this study was to identify loci underlying variation in FEC, as an indicator of nematode resistance, in a joint analysis using data from three populations (Scottish Blackface, Sarda × Lacaune and Martinik Black-Belly × Romane), genotyped with the ovine 50k SNP chip. The trait analysed was the average animal effect for Strongyles and Nematodirus FEC data. Analyses were performed with regional heritability mapping (RHM), fitting polygenic effects with either the whole genomic relationship matrix or matrices excluding the chromosome being interrogated. Across-population genomic covariances were set to zero. After quality control, 4123 animals and 38 991 SNPs were available for the analysis. RHM identified genome-wide significant regions on OAR4, 12, 14, 19 and 20, with the latter being the most significant. The OAR20 region is close to the major histocompatibility complex, which has often been proposed as a functional candidate for nematode resistance. This region was significant only in the Sarda × Lacaune population. Several other regions, on OAR1, 3, 4, 5, 7, 12, 19, 20 and 24, were significant at the suggestive level.
Asunto(s)
Resistencia a la Enfermedad/genética , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/genética , Animales , Cruzamiento , Europa (Continente) , Heces/parasitología , Genotipo , Infecciones por Nematodos/genética , Infecciones por Nematodos/inmunología , Recuento de Huevos de Parásitos , Polimorfismo de Nucleótido Simple , Ovinos/genética , Ovinos/parasitología , Enfermedades de las Ovejas/inmunologíaRESUMEN
The genetic architecture underlying nematode resistance and body weight in Blackface lambs was evaluated comparing genome-wide association (GWA) and regional heritability mapping (RHM) approaches. The traits analysed were faecal egg count (FEC) and immunoglobulin A activity against third-stage larvae from Teladorsagia circumcincta, as indicators of nematode resistance, and body weight in a population of 752 Scottish Blackface lambs, genotyped with the 50k single-nucleotide polymorphism (SNP) chip. FEC for both Nematodirus and Strongyles nematodes (excluding Nematodirus), as well as body weight were collected at approximately 16, 20 and 24 weeks of age. In addition, a weighted average animal effect was estimated for both FEC and body weight traits. After quality control, 44 388 SNPs were available for the GWA analysis and 42 841 for the RHM, which utilises only mapped SNPs. The same fixed effects were used in both analyses: sex, year, management group, litter size and age of dam, with day of birth as covariate. Some genomic regions of interest for both nematode resistance and body weight traits were identified, using both GWA and RHM approaches. For both methods, strong evidence for association was found on chromosome 14 for Nematodirus average animal effect, chromosome 6 for Strongyles FEC at 16 weeks and chromosome 6 for body weight at 16 weeks. Across the entire data set, RHM identified more regions reaching the suggestive level than GWA, suggesting that RHM is capable of capturing some of the variation not detected by GWA analyses.
Asunto(s)
Peso Corporal/genética , Resistencia a la Enfermedad/genética , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/genética , Oveja Doméstica/genética , Animales , Femenino , Estudio de Asociación del Genoma Completo , Inmunoglobulina A/genética , Masculino , Infecciones por Nematodos/genética , Nematodirus/aislamiento & purificación , Nematodirus/patogenicidad , Ostertagia/patogenicidad , Recuento de Huevos de Parásitos , Polimorfismo de Nucleótido Simple , Ovinos , Enfermedades de las Ovejas/parasitología , Oveja Doméstica/parasitologíaRESUMEN
Historically, sheep have been selectively bred for desirable traits including wool characteristics. However, recent moves towards extensive farming and reduced farm labour have seen a renewed interest in Easycare breeds. The aim of this study was to quantify the underlying genetic architecture of wool shedding in an Easycare flock. Wool shedding scores were collected from 565 pedigreed commercial Easycare sheep from 2002 to 2010. The wool scoring system was based on a 10-point (0-9) scale, with score 0 for animals retaining full fleece and 9 for those completely shedding. DNA was sampled from 200 animals of which 48 with extreme phenotypes were genotyped using a 50-k SNP chip. Three genetic analyses were performed: heritability analysis, complex segregation analysis to test for a major gene hypothesis and a genome-wide association study to map regions in the genome affecting the trait. Phenotypes were treated as a continuous or binary variable and categories. High estimates of heritability (0.80 when treated as a continuous, 0.65-0.75 as binary and 0.75 as categories) for shedding were obtained from linear mixed model analyses. Complex segregation analysis gave similar estimates (0.80 ± 0.06) to those above with additional evidence for a major gene with dominance effects. Mixed model association analyses identified four significant (P < 0.05) SNPs. Further analyses of these four SNPs in all 200 animals revealed that one of the SNPs displayed dominance effects similar to those obtained from the complex segregation analyses. In summary, we found strong genetic control for wool shedding, demonstrated the possibility of a single putative dominant gene controlling this trait and identified four SNPs that may be in partial linkage disequilibrium with gene(s) controlling shedding.
Asunto(s)
Cruzamiento/métodos , Fenotipo , Selección Genética/genética , Ovinos/genética , Ovinos/fisiología , Lana/crecimiento & desarrollo , Animales , Estudio de Asociación del Genoma Completo , Genotipo , Modelos Lineales , Análisis de Secuencia por Matrices de Oligonucleótidos/veterinaria , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Genes involved in the physiological control of energy and triglyceride synthesis, such as malic enzyme 1, NADP(+)-dependent, cytosolic (ME1) and nuclear receptor subfamily 0, group B, member 2 (NR0B2), are key candidates that may have effects on meat and carcass quality traits. These genes were sequenced in Aberdeen Angus beef cattle, and the possibility of associations between SNPs and economically important carcass and meat quality traits was tested. Six novel SNPs, five in ME1 and one in NR0B2, were identified. A SNP in exon eight of ME1 resulted in a non-synonymous amino acid change from valine to isoleucine. Phenotypic data were recorded on 536 commercial Aberdeen Angus-cross beef cattle, which comprised 28 carcass quality, tenderness and sensory traits. The majority of the SNPs were associated with at least one of these traits, including an association between the NR0B2 SNP and fat class, and associations between at least one of the ME1 SNPs and eye muscle area, sirloin weight before maturation, sirloin steak tail length, and juiciness.
Asunto(s)
Bovinos/genética , Malato Deshidrogenasa/genética , Carne , Receptores Nucleares Huérfanos/genética , Animales , Femenino , MasculinoRESUMEN
We have used linkage disequilibrium (LD) to identify single nucleotide polymorphisms (SNPs) on the Illumina Equine SNP50 BeadChip, which may be incorrectly positioned on the genome map. A total of 1201 Thoroughbred horses were genotyped using the Illumina Equine SNP50 BeadChip. LD was evaluated in a pairwise fashion between all autosomal SNPs, both within and across chromosomes. Filters were then applied to the data, firstly to identify SNPs that may have been mapped to the wrong chromosome and secondly to identify SNPs that may have been incorrectly positioned within chromosomes. We identified a single SNP on ECA28, which showed low LD with neighbouring SNPs but considerable LD with a group of SNPs on ECA10. Furthermore, a cluster of SNPs on ECA5 showed unusually low LD with surrounding SNPs. A total of 39 SNPs met the criteria for unusual within-chromosome LD. The results of this study indicate that some SNPs may be misplaced. This finding is significant, as misplaced SNPs may lead to difficulties in the application of genomic methods, such as homozygosity mapping, for which SNP order is important.
Asunto(s)
Mapeo Cromosómico/métodos , Caballos/genética , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia de ADNRESUMEN
This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome-wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half-sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti-Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti-L3, and IgE anti-ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.
Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de las Cabras/inmunología , Infecciones por Nematodos/veterinaria , Sitios de Carácter Cuantitativo , Animales , Cromosomas de los Mamíferos/genética , Femenino , Tracto Gastrointestinal/parasitología , Genotipo , Enfermedades de las Cabras/genética , Cabras/genética , Hemoncosis/inmunología , Hemoncosis/parasitología , Hemoncosis/veterinaria , Haemonchus/inmunología , Masculino , Repeticiones de Microsatélite , Infecciones por Nematodos/genética , Infecciones por Nematodos/inmunología , Esofagostomiasis/inmunología , Esofagostomiasis/parasitología , Esofagostomiasis/veterinaria , Oesophagostomum/inmunología , Tricostrongiliasis/inmunología , Tricostrongiliasis/parasitología , Tricostrongiliasis/veterinaria , Trichostrongylus/inmunologíaRESUMEN
Theory hypothesizes that the rate of decline in linkage disequilibrium (LD) as a function of distance between markers, measured by r(2), can be used to estimate effective population size (N(e)) and how it varies over time. The development of high-density genotyping makes feasible the application of this theory and has provided an impetus to improve predictions. This study considers the impact of several developments on the estimation of N(e) using both simulated and equine high-density single-nucleotide polymorphism data, when N(e) is assumed to be constant a priori and when it is not. In all models, estimates of N(e) were highly sensitive to thresholds imposed upon minor allele frequency (MAF) and to a priori assumptions on the expected r(2) for adjacent markers. Where constant N(e) was assumed a priori, then estimates with the lowest mean square error were obtained with MAF thresholds between 0.05 and 0.10, adjustment of r(2) for finite sample size, estimation of a [the limit for r(2) as recombination frequency (c) approaches 0] and relating N(e) to c (1 - c/2). The findings for predicting N(e) from models allowing variable N(e) were much less clear, apart from the desirability of correcting for finite sample size, and the lack of consistency in estimating recent N(e) (<7 generations) where estimates use data with large c. The theoretical conflicts over how estimation should proceed and uncertainty over where predictions might be expected to fit well suggest that the estimation of N(e) when it varies be carried out with extreme caution.
Asunto(s)
Desequilibrio de Ligamiento , Modelos Genéticos , Animales , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Técnicas de Genotipaje , Caballos/genética , Polimorfismo de Nucleótido Simple/genética , Densidad de PoblaciónRESUMEN
This study aimed at verifying previously identified QTL affecting growth and carcass traits on ovine chromosome 18 (OAR18) in Texel sheep (n = 1844), and on OAR1 in Charollais (n = 851) and Suffolk (n = 998) sheep. The QTL were investigated using regression and variance component mapping (VCA) of body weight, muscle and fat depth measurements. In addition, the mode of inheritance of the Texel OAR18 QTL was explored, using data from 4376 Texel sheep, fitting VCA models testing for additive and imprinting effects. We also simulated a 480-sheep population with different QTL imprinting models and various available levels of marker information to understand the behaviour of the VCA results under different assumed genetic models. In summary, the previously identified QTL were successfully verified using both interval mapping and VCA in the three breeds. We propose a polar overdominance mode of inheritance for the OAR18 QTL in Texel sheep, and we present methods to dissect the QTL mode of inheritance, using the Texel OAR18 QTL as an example.
Asunto(s)
Composición Corporal/genética , Sitios de Carácter Cuantitativo/genética , Oveja Doméstica/genética , Ovinos/genética , Tejido Adiposo/crecimiento & desarrollo , Animales , Peso Corporal/genética , Cruzamiento , Mapeo Cromosómico/veterinaria , Femenino , Masculino , Modelos Genéticos , Desarrollo de Músculos/genética , Fenotipo , Análisis de Regresión , Ovinos/crecimiento & desarrollo , Oveja Doméstica/crecimiento & desarrollo , Especificidad de la EspecieRESUMEN
Interferon regulatory factor 7 (IRF7), as a key regulator of type I interferon response, plays an important role during innate response against viral infection. Although well conserved across species, the structure of IRF7 and its function during parasite infection are not well documented in farm animals, such as the pig. To bridge this gap, we have determined the porcine IRF7 gene structure and identified two intronic single nucleotide polymorphisms (SNPs), SNP g.748G>C and SNP g.761A>G, in commercial pig breeds. The distribution of SNP g.761A>G in multiple breeds suggested that it was in Hardy-Weinberg equilibrium and allowed us to map it at the top of SSC2. We found that during Sarcocystis miescheriana infection, the G allele was associated with high lymphocyte levels (P < 0.02), reduced drop in platelet levels (P < 0.002) and IgG1-Th2-dominated response (P < 0.05). This suggests that the G allele was associated with better health and immunity of the host during Sarcocystis infection. Furthermore, we have also provided suggestive evidence that the G allele of SNPc.761A>G enhances the transactivation activity of IRF7, possibly by improving IRF7 transcript splicing of intron-3. These findings would suggest that IRF7, as a transcriptional regulator, is involved in the defence mechanism against a larger spectrum of pathogens, and in more host species, than initially anticipated.
Asunto(s)
Factor 7 Regulador del Interferón/genética , Fenotipo , Sarcocistosis/veterinaria , Transducción de Señal/inmunología , Sus scrofa/genética , Enfermedades de los Porcinos/genética , Enfermedades de los Porcinos/parasitología , Animales , Secuencia de Bases , Clonación Molecular , Cartilla de ADN/genética , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Intrones/genética , Modelos Lineales , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcocistosis/genética , Análisis de Secuencia de ADN , Transducción de Señal/genética , Sus scrofa/inmunología , PorcinosRESUMEN
The prevalence of bovine tuberculosis (BTB) in the UK remains a significant economic burden and problem for the agri-food industry. Much effort has been directed towards improving diagnostics, finding vaccine candidates and assessing the usefulness of badger culling. The contribution that host genotype makes to disease outcome has, until recently, been overlooked; yet, it is biologically untenable that genetic variation does not play a role. In this review, we highlight the evidence, past and present, for a role of host genetics in determining susceptibility to BTB in livestock. We then address some of the major issues surrounding the design of future studies tasked with finding the exact causative genetic variation underpinning the TB susceptibility phenotype. Finally, we discuss some of the potential future benefits, and problems, that a knowledge of the genetic component to BTB resistance/susceptibility may bring to the agricultural industries and the wider scientific community.
Asunto(s)
Enfermedades de los Bovinos/genética , Predisposición Genética a la Enfermedad/genética , Tuberculosis Bovina/genética , Animales , Bovinos/genética , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Variación Genética , Ganado/genética , Mycobacterium bovis/patogenicidad , Especificidad de la Especie , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/microbiología , Tuberculosis Bovina/prevención & controlRESUMEN
Infectious pancreatic necrosis (IPN) is a viral disease with a significant negative impact on the global aquaculture of Atlantic salmon. IPN outbreaks can occur during specific windows of both the freshwater and seawater stages of the salmon life cycle. Previous research has shown that a proportion of the variation seen in resistance to IPN is because of host genetics, and we have shown that major quantitative trait loci (QTL) affect IPN resistance at the seawater stage of production. In the current study, we completed a large freshwater IPN challenge experiment to allow us to undertake a thorough investigation of the genetic basis of resistance to IPN in salmon fry, with a focus on previously identified QTL regions. The heritability of freshwater IPN resistance was estimated to be 0.26 on the observed scale and 0.55 on the underlying scale. Our results suggest that a single QTL on linkage group 21 explains almost all the genetic variation in IPN mortality under our experimental conditions. A striking contrast in mortality is seen between fry classified as homozygous susceptible versus homozygous resistant, with QTL-resistant fish showing virtually complete resistance to IPN mortality. The findings highlight the importance of the major QTL in the genetic regulation of IPN resistance across distinct physiological lifecycle stages, environmental conditions and viral isolates. These results have clear scientific and practical implications for the control of IPN.
Asunto(s)
Susceptibilidad a Enfermedades/veterinaria , Enfermedades de los Peces/genética , Enfermedades Pancreáticas/veterinaria , Sitios de Carácter Cuantitativo , Salmo salar/genética , Animales , Mapeo Cromosómico , Enfermedades de los Peces/transmisión , Agua Dulce , Genotipo , Repeticiones de Microsatélite , Necrosis , Enfermedades Pancreáticas/genéticaRESUMEN
IgA and IgE activity against Teladorsagia circumcincta was investigated in a flock of Texel lambs following natural, mixed nematode infection among lambs. The distribution of IgA activity was similar to a gamma distribution whereas IgE activity was different. Box-Cox analysis demonstrated that X0.25 was a suitable transformation to normalise IgE responses. The transformed IgE activity was under moderate to strong genetic control. Nine different allergens were identified by proteomic analysis. Tropomyosin was selected for further analysis. IgE activity against tropomyosin was moderately heritable and associated with decreased egg counts and with reduced body weight at the time of sampling.
Asunto(s)
Alérgenos/inmunología , Antígenos Helmínticos/inmunología , Variación Genética , Inmunoglobulina E/sangre , Enfermedades de las Ovejas/parasitología , Trichostrongyloidea/genética , Tricostrongiloidiasis/veterinaria , Alérgenos/química , Alérgenos/genética , Animales , Antígenos Helmínticos/química , Antígenos Helmínticos/genética , Peso Corporal , Ensayo de Inmunoadsorción Enzimática , Heces/parasitología , Femenino , Larva/crecimiento & desarrollo , Larva/inmunología , Masculino , Recuento de Huevos de Parásitos , Proteómica , Ovinos/parasitología , Enfermedades de las Ovejas/genética , Enfermedades de las Ovejas/inmunología , Trichostrongyloidea/clasificación , Trichostrongyloidea/crecimiento & desarrollo , Trichostrongyloidea/inmunología , Tricostrongiloidiasis/genética , Tricostrongiloidiasis/inmunología , Tricostrongiloidiasis/parasitología , Tropomiosina/química , Tropomiosina/genética , Tropomiosina/inmunologíaRESUMEN
Many genomic methodologies rely on the presence and extent of linkage disequilibrium (LD) between markers and genetic variants underlying traits of interest, but the extent of LD in the horse has yet to be comprehensively characterized. In this study, we evaluate the extent and decay of LD in a sample of 817 Thoroughbreds. Horses were genotyped for over 50,000 single nucleotide polymorphism (SNP) markers across the genome, with 34,848 autosomal SNPs used in the final analysis. Linkage disequilibrium, as measured by the squared correlation coefficient (r(2)), was found to be relatively high between closely linked markers (>0.6 at 5 kb) and to extend over long distances, with average r(2) maintained above non-syntenic levels for single nucleotide polymorphisms (SNPs) up to 20 Mb apart. Using formulae which relate expected LD to effective population size (N(e)), and assuming a constant actual population size, N(e) was estimated to be 100 in our population. Values of historical N(e), calculated assuming linear population growth, suggested a decrease in N(e) since the distant past, reaching a minimum twenty generations ago, followed by a subsequent increase until the present time. The qualitative trends observed in N(e) can be rationalized by current knowledge of the history of the Thoroughbred breed, and inbreeding statistics obtained from published pedigree analyses are in agreement with observed values of N(e). Given the high LD observed and the small estimated N(e), genomic methodologies such as genomic selection could feasibly be applied to this population using the existing SNP marker set.
Asunto(s)
Caballos/genética , Desequilibrio de Ligamiento , Animales , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Linaje , Densidad de PoblaciónRESUMEN
To dissect age-dependent quantitative trait loci (QTL) associated with growth and to examine changes in QTL effects over time, the Gompertz growth model was fitted to longitudinal live weight data on 788 Scottish Blackface lambs from nine half-sib families. QTL were mapped for model parameters and weekly live weights and growth rates using microsatellite markers on chromosomes 1, 2, 3, 5, 14, 18, 20 and 21. QTL significance (using alpha = 0.05 chromosome-wide significance thresholds, unless otherwise stated) varied with age, and those for growth rate occurred earlier than equivalent QTL for live weight. A chromosome 20 QTL for growth rate was significant from 4 to 9 weeks (maximum significance at 6 weeks) and for maximum growth rate. For live weight, this QTL was significant from 8 to 16 weeks (maximum significance at 12 weeks). A nominally significant chromosome 14 QTL was detected for growth rates from birth to week 2 in the same families and location as an 8-week weight QTL. In addition, at the same position on chromosome 14, a QTL was significant for growth rate for 17-28 weeks (maximum significance at 24 weeks). A chromosome 3 QTL was significant for weights at early ages (birth to week 4) and a growth rate QTL on chromosome 18 was significant from 8 to 12 weeks. Fitting growth curves allowed the combination of information from multiple measurements into a few biologically meaningful variables, and the detection of growth QTL that were not observed from analyses of raw weight data. These QTL describe distinct parts of an animal's growth curve trajectory, possibly enabling manipulation of this trajectory.