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1.
Detecting some of the genes that influence disease resistance would improve our understanding of the processes that cause disease and also simplify disease control. Genes within the major histocompatibility complex (mhc) are strong candidates for disease resistance and they have been intensely studied for the last 30 years. Recently, several groups working independently have reported the existence of alleles within the mhc that are associated with enhanced resistance to nematode infection. This article uses hindsight to describe some of the potential pitfalls that hinder the search for valid disease resistance genes. The search requires a good understanding of disease biology, molecular genetics, statistical genetics and especially, the design and analysis of experiments. The power to detect mhc effects is quite low and is quite sensitive to the frequency of the putative resistance alleles.  相似文献   

2.
In this paper we describe the use of polymorphic genes affecting coat colour as a tool in diversity studies of domestic animals. Although phenotypic data has been the main criteria for establishing different breeds, calculation of genetic distances between breeds is normally performed using noncoding microsatellite markers. As anticipated, MC1‐R (melanocyte stimulating hormone receptor) allele frequencies vary greatly between cattle breeds expressing different coat colours. In multicoloured breeds, like Icelandic cattle, a high frequency of the E+ allele appears to be essential for colour variation. Whereas black breeds have a high frequency of the dominant acting allele ED, entirely red breeds have no ED. Animals being homozygous for the defective allele e occurred frequently in some cattle breeds, indicating that the MC1‐R does not have crucial impact on animal physiology other than coat colour. The E+ and e alleles were observed in the closely related river buffalo as well. None of the breeds included in this study express the roan phenotype. Consequently, they were monomorphic at the MGF locus. As for the MC1‐R locus, a correlation to colour pattern was observed for two c‐kit alleles as well, confirming that selection of specific phenotypes strongly affect the allelic variation of underlying loci. Information on genes affecting the phenotype is therefore well suited for describing different breeds of livestock and, consequently, a practical tool in breed conservation.  相似文献   

3.
Benzimidazole resistance is a common problem in parasitic nematodes of ruminants and early detection is vital if its spread is to be monitored and controlled. Real time PCR offers a fast and reliable method for rapid detection and measurement of resistance allele frequencies. In Haemonchus contortus a single nucleotide polymorphism at codon 200 of the beta-tubulin gene (TTC to TAC), causing a phenylalanine to tyrosine amino acid substitution, has been shown to be involved in many cases of resistance. Locked nucleic acid (LNA) Taqman probes have been used in this work to detect and measure the frequency of resistance alleles in individual and multiple H. contortus. Detection of resistant genotypes using LNA Taqman probes in individual H. contortus is simpler and more reliable than with previously described assays. Measurement of the frequency of resistant alleles in populations of H. contortus was achieved by using the cycle threshold (C(t)) values and a standard curve derived from populations with known allele frequencies. Results using the LNA probes on individual and multiple worms gave similar results to the allele specific PCR. The sensitivity of the LNA assay on multiple nematodes allowed reliable detection of > or = 10% resistance allele frequency. Using the final fluorescence method, it was possible to differentiate populations with approximately 0, 5 and 10% resistance allele frequencies.  相似文献   

4.
OBJECTIVE: To develop new and improved tests to detect alleles at codons 136 and 171 of the ovine prion protein locus and to evaluate the frequency of these alleles. ANIMALS: 159 Suffolk sheep belonging to 3 flocks. PROCEDURE: Polymerase chain reaction (PCR) analysis that contained diagnostic restriction site variation for each allele were developed for the relevant gene regions. Alleles were determined by analyzing DNA isolated from buccal swab specimens or blood samples. RESULTS: At codon 136, frequencies of the alanine and valine alleles were found to be 97 and 3%, respectively. At codon 171, frequencies of the glutamine, arginine, and histidine alleles were found to be 57, 41, and 2%, respectively. CONCLUSIONS: Little variation was detected in codon 136, whereas noteworthy variation was found in codon 171; > 40% of the alleles at this locus coded for glutamine. Because the glutamine allele at codon 171 confers susceptibility to scrapie, reduction of its frequency is of importance to management of sheep flocks. CLINICAL RELEVANCE: Genotyping of sheep, using the tests reported here, should facilitate selective breeding programs designed to decrease the risk of scrapie.  相似文献   

5.
Hypertrophic osteodystrophy (HOD) is a canine bone disease that affects mainly large breed dogs, including the Weimaraner, and studies have shown a link between recent vaccination with a modified live virus and the onset of HOD in this breed. In humans, it has been suggested that human leukocyte antigen (HLA) alleles can influence antibody response to vaccination. The aim of this study was to investigate whether there is an association between the development of HOD in Weimaraners and MHC alleles at the DLA-DQA1 locus in a group of 33 unrelated dogs. The DQA1 allele and genotype frequencies were determined by sequence-based typing. Although clinical signs developed within six weeks of vaccination in all 12 dogs for which information was available, no association was found between DQA1 alleles and HOD in this population of Weimaraner dogs. A role for other immune-response genes in the pathogenesis of HOD should not however be ruled out. Whereas recent vaccination may be a trigger for the disease, it was concluded that there is no specific vaccine that is most responsible for the expression of the disease.  相似文献   

6.
Weimaraner dogs are defined by light brown coat colour termed grey including several shadings ranging from silver and deer to mouse grey. In contrast, the so-called blue Weimaraners (BW) with lightened black-pigmented coat have been proposed to represent spontaneous revertants in the Weimaraner breed. In order to investigate the genetic determinants of the characteristic grey coat colour versus those of BW, known variation in coat colour genes including TYRP1 and MLPH were analysed in a number of grey and blue dogs. Variations at the B locus cause grey coat colour in Weimaraners via two non-functional TYRP1 copies (bb) including the b(s), b(d) and b(c) alleles. In all BW, at least one functional TYRP1 allele (Bb or BB genotype) was identified. Defined microsatellite alleles in TYRP1 intron 4 are linked to this functional B allele in BW. These alleles were also detected in various other dog breeds, but not in grey Weimaraners. The combination of a dominant trait for blue versus grey together with a specific TYRP1 haplotype in BW suggests that blue coat colour is not the result of spontaneous (back-) mutation in grey Weimaraners. This inference is even emphasized by the presence of a unique Y-chomosomal haplotype in a male offspring of the supposed ancestor of the BW population which - according to pedigree information - carries a copy of the original Y chromosome. Thus, molecular genetic analyses of coat colours combined with Y-chromosomal haplotypes allow tracing the origin of atypical dogs in respective canine populations.  相似文献   

7.
The selection of sheep that are resistant to gastrointestinal parasites and have lower faecal egg counts (FECs) has been the subject of extensive research. This has led to the speculation that the Major Histocompatibility Complex (MHC) genes could be used as markers to reduce FEC. In this study, associations between variation in ovine MHC-DQA2 and various measures of FEC recorded at two times (approximately 4 and 9 months of age) were investigated in a large group of New Zealand lambs (n=4676), derived from 185 different sire-lines, of a variety of breeds and raised on 25 separate farms. Pair-sample t-tests revealed that FEC for Nematodirus spp., Strongyle spp. and total FEC differed significantly between the two assessments. A total of twenty one DQA2 alleles or DQA2-DQA2-like haplotypes were identified, with allele/haplotype presence and frequency varying significantly between farms. For example, allele *0103 was observed on all farms, ranging in frequency from 0.2 to 60.9%, while haplotype *0101-*1601 was only present on one farm, in two lambs. A number of associations between the presence/absence of these alleles and egg counts were observed, but nearly all the allelic/haplotypic associations were age and parasite specific, suggesting that immune response is both age and challenge (parasite species mix) dependent. The exception was allele *1201 which was associated with increased total FECs at both 4 and 9 months of age; with it either being, or tending toward being, significantly associated with both increased Strongyle spp. and Nematodirus spp. counts as well. However, the observed increases in egg counts were small and ranged between 5 and 32 eggs per gram. In conclusion, we believe that the MHC plays an important role in parasite resistance, but that the MHC-nematode interaction is complex and thus the development of a single gene-marker based on the "MHC effect" is unlikely.  相似文献   

8.
Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had >9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.  相似文献   

9.
ABSTRACT: The application of genetic breeding programmes to eradicate transmissible spongiform encephalopathies in goats is an important aim for reasons of animal welfare as well as human food safety and food security. Based on the positive impact of Prnp genetics on sheep scrapie in Europe in the past decade, we have established caprine Prnp gene variation in more than 1100 goats from the United Kingdom and studied the association of Prnp alleles with disease phenotypes in 150 scrapie-positive goats. This investigation confirms the association of the Met142 encoding Prnp allele with increased resistance to preclinical and clinical scrapie. It reveals a novel association of the Ser127 encoding allele with a reduced probability to develop clinical signs of scrapie in goats that are already positive for the accumulation of disease-specific prion protein in brain or periphery. A United Kingdom survey of Prnp genotypes in eight common breeds revealed eleven alleles in over thirty genotypes. The Met142 encoding allele had a high overall mean allele frequency of 22.6%, whereas the Ser127 encoding allele frequency was considerably lower with 6.4%. In contrast, a well known resistance associated allele encoding Lys222 was found to be rare (0.9%) in this survey. The analysis of Prnp genotypes in Mexican Criollas goats revealed nine alleles, including a novel Phe to Leu substitution in codon 201, confirming that high genetic variability of Prnp can be found in scrapie-free populations. Our study implies that it should be feasible to lower scrapie prevalence in goat herds in the United Kingdom by genetic selection.  相似文献   

10.
The aim of this paper was to explore the effect of genetic heterogeneity in host resistance to infection on the population-level risks and outcomes of epidemics. This was done using a stochastic epidemiological model in which the model parameters were assumed to be genetically controlled traits of the host. A finite locus model was explored, with a gene controlling the transmission coefficient (i.e., host susceptibility to infection) and a gene controlling the recovery period. Both genes were simulated to have 2 alleles with underlying additive or dominance inheritance and an independent assortment of alleles. The model was parameterized for a viral pig disease (transmissible gastroenteritis), and complete homogeneous mixing among genotypes was assumed. Mean population genotype dramatically affected epidemic outcomes, and subtle effects of heterogeneity on epidemic properties were also observed. Genetic variation in the transmission coefficient led to probabilities of epidemics occurring that were slightly greater than expected, but genetic variation in the recovery rate had no such effect. Epidemics were generally less severe in genetically heterogeneous populations than expected from the constituent subpopulations. Furthermore, the genotype of the initial infected animal had a marked effect on epidemic probabilities, particularly when genetic variation was for recovery rate. The results of this model provide useful information to determine the optimum population structures and to exploit genetic variation in resistance to infection. Applications of the proposed model in genetically heterogeneous populations for identifying practical disease management strategies are also discussed.  相似文献   

11.
The association of a diallelic polymorphism in the leukemia inhibitory factor (LIF) gene with reproductive, growth, and carcass traits was studied in a German synthetic pig line. The diallelic SNP has been located in the 3'-untranslated region of the third exon of the porcine LIF gene. Information on 955 litter records from 273 genotyped sows was used in the analyses with respect to the number of piglets born alive. To identify possible pleiotropic marker effects, the growth and carcass traits ADG and backfat thickness were tested for associations with the SNP within the LIF gene in this population. At the LIF locus, the allele frequencies were 0.27 for the A allele and 0.73 for the B allele. There was an indication of an additive effect on the number of piglets born alive, and a significant dominance effect of the B allele was observed for first, second, and third to 10th parities (P = 0.044). The dominance effect for the first parity amounted to -0.73 +/- 0.36 (P = 0.047). No associations were detected between the marker alleles and the growth and carcass traits.  相似文献   

12.
The susceptibility of sheep to scrapie is under the control of the host’s prion protein (PrP) gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 154 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and the USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report the results of a multi-flock study showing the protective effect of polymorphisms other than those at codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 378 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the PrP gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT137RQ and ARQK176 alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene.  相似文献   

13.
Cyathostomins are the primary parasitic pathogens of equids. For over 40 years, these nematodes have been controlled using broad spectrum anthelmintics. Three classes of anthelmintic are currently available for this use but, unfortunately, resistance to each of these has now been recorded in cyathostomin populations. As part of an optimal strategy to control cyathostomin infections in the field, it will be important to identify drug-resistant worms at as early a stage as possible. This objective needs to be supported by methodologies that will allow the accurate comparison of anthelmintic resistance in different nematode populations. At present, the faecal egg count reduction test is considered the most suitable method for initial screening for anthelmintic resistance in equine nematode populations. However, in its current state, this test lacks sensitivity. It is also costly and time-consuming to perform. Laboratory-based techniques, such as the egg hatch assay, larval development assay, larval migration inhibition assay and the larval feeding inhibition assay offer alternative options for assessing anthelmintic resistance in nematode populations. All of these tests have been investigated for their utility in measuring drug resistance in sheep nematode populations and some have proven useful. The egg hatch assay, larval development assay and larval migration inhibition assay have been investigated for use in measuring levels of drug resistance in equine nematode populations. However, at best, the results obtained thus far indicate that these tests require further refinement.  相似文献   

14.
Genetic distance is used to classify and elucidate the evolutionary relationship between populations, such as species, which have been diverging for a long period. The properties of genetic distance measures in livestock classification have hitherto not been investigated. We used simulation studies to compare the accuracy of eight genetic distance measures to classify recently diverged populations. The effect of varied population sizes from generation to generation were also taken into account. Comparatively better results are obtained from Nei's standard distance with two alleles at each locus and from Nei's DA distance with four alleles at each locus under various conditions. However, the difference in accuracy among distance measures was small and very high correlations were shown. The number of alleles at each locus had a greater effect on accuracy than the number of loci or type of distance measures. It indicates that highly polymorphic markers, such as DNA microsatellite, are powerful tool to improve the accuracy in classification of domestic animals. The six distance measures had a linear relationship with generation number at constant population size. None of the distance measures, however, showed a linear relationship when population size varied. The effect of fluctuating population size on the average distance was obvious over the first few generations but declined when the number of generations was increased.  相似文献   

15.
Various canine breeds are remarkably different from each other not only in their sizes and shapes but also in behavioral traits, suggesting that some of them are under genetic control. Although dopaminergic neurotransmission system is considered to affect animal behavior, little is known about related genes in canine. Relations between specific alleles in polymorphic regions of the dopamine receptor D4 gene (DRD4) and personality or psychiatric disorders have been reported in humans, and we first found polymorphism in exon III region of the gene in 4 canine breeds. In this study we surveyed allele frequency distribution in 23 breeds including a total of 1,535 unrelated individuals. In exon III, 8 alleles including a novel allele were identified. A group of breeds in which the alleles 447b, 498 and 549 were frequent tended toward high scores in aggression-related behavioral traits than that with frequent alleles 435 and 447a. Moreover, a polymorphism based on 24 bp insertion/deletion was found in exon I region for the first time in dogs. This information may be of use for candidate gene studies of behavioral variation in dogs.  相似文献   

16.
Sheep possessing alleles for the prion protein with glutamine (Q) or histidine, both reported as Q, at codon 171 are highly susceptible to scrapie. Incidence of scrapie infection is rare when animals possess at least one allele for arginine (R) at codon 171. The current USDA APHIS scrapie eradication program utilizes genotyping for alleles that confer resistance to scrapie. Although it has not been a criterion of registration, genotyping has been utilized in the University of Wyoming Ram Performance test since 2002. Performance test records from 2002 to 2006 (n=518) were analyzed to determine if any production loss or benefit was associated with scrapie resistance in rams. Performance of rams with scrapie resistant genotypes was equal to or better than scrapie susceptible rams. Based on test performance as an acceptable indicator of sire superiority, selection for rams with scrapie resistant genotypes should not negatively impact flock performance.  相似文献   

17.
Scrapie is an ovine transmissible spongiform encephalopathy, and its susceptibility is associated with polymorphisms in the prion protein gene (PRNP). Genetic selection is currently the most effective mean for eradication of the susceptible VRQ allele in favour of resistant ARR allele. Maintenance of genetic diversity should be one of the major objectives in breeding programmes, especially in endangered breeds, and genetic information are an excellent alternative to pedigree data where these information are missing. The aim of our study was to determine changes of genetic variability in six native sheep breeds from autonomous province of Bolzano, northern Italy, following simulation of scrapie selection scenarios. A total of 684 rams were investigated for PRNP polymorphisms and for 10 microsatellite loci to estimate genetic variability. Across all loci, a total of 163 alleles were detected with a mean of 10.4 alleles per locus. Average observed (Ho) and unbiased expected (uHe) heterozygosity overall loci were 0.74 and 0.78, respectively, showing a statistically significant deviation from Hardy–Weinberg equilibrium (HWE) in all breeds. This heterozygosity deficit was confirmed by a positive fixation index (Fis), determining a moderate inbreeding in each breed. Simulating a soft selection, where only rams having at least a VRQ allele should be excluded from reproduction, Ho, uHe and Fis values remained almost unchanged, indicating that genetic variability should not be affected by the removal of these individuals. With a mild selection scenario, considering only rams with at least one ARR allele, we observed a decrease in the mean alleles per breed (8.9) and the maintenance of heterozygosity deficiency, except for two breeds, where it was any longer significant. These results showed that selection strategies allowing use of heterozygous as well homozygous ARR rams might be the right compromise to improve resistance to scrapie and to do not dramatically affect genetic variability of these breeds.  相似文献   

18.
Three anthelmintic classes with distinct mechanisms of action are commercially available. Selection of nematode populations resistant to all these drugs has occurred, particularly in trichostrongyloid parasites of sheep. Anthelmintic resistance in cattle parasites has only recently been recognized and appears to be less pronounced, even though very similar species infect both hosts. To understand the bases for differences in the rate of resistance development in sheep versus cattle parasites, it is important to first demonstrate that the same kinds of resistance alleles exist in both. The benzimidazoles (BZ), which have been used for more than 40 years, were chosen as an example. BZ-sensitive (BZ(S)) and BZ-resistant (BZ(R)) nematodes that parasitize sheep have been distinguished at the molecular level by a single nucleotide change in the codon for amino acid 200 of a beta-tubulin gene, a switch from TTC (phenylalanine) to TAC (tyrosine). PCR primers were designed to completely conserved regions of trichostrongyloid beta-tubulin genes and were used to amplify DNA fragments from Haemonchus contortus (cDNA from a BZ(S) and a BZ(R) library) as positive controls. The technique was then extended to the cattle parasites, Cooperia oncophora and Ostertagia ostertagi (from genomic DNA). Sequence analysis proved the presence of amplified BZ(S) alleles in all three species and BZ(R) alleles in the BZ(R) population of H. contortus. Based on these data, nested PCR primers using the diagnostic T or A as the most 3' nucleotide were designed for each species. Conditions for selective PCR were determined. To demonstrate feasibility, genomic DNA was recovered from individual H. contortus L(3) larvae from both BZ(S) and BZ(R) populations. Genomic DNA was also isolated from >70 individual adult male C. oncophora collected from a cattle farm in New Zealand with reported BZ resistance. Allele-specific PCR discriminated among heterozygotes and homozygotes in both species. This method could find utility in studying the molecular epidemiology of BZ resistance in cattle parasites and for defining the variables that limit the development and spread of anthelmintic resistance in this host.  相似文献   

19.
Sea otters (Enhydra lutris) have been reported to become infected with Toxoplasma gondii and at times succumb to clinical disease. Here, we determined genotypes of 39 T. gondii isolates from 37 sea otters in two geographically distant locations (25 from California and 12 from Washington). Six genotypes were identified using 10 PCR-RFLP genetic markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico, and by DNA sequencing of loci SAG1 and GRA6 in 13 isolates. Of these 39 isolates, 13 (33%) were clonal Type II which can be further divided into two groups at the locus Apico. Two of the 39 isolates had Type II alleles at all loci except a Type I allele at locus L358. One isolate had Type II alleles at all loci except the Type I alleles at loci L358 and Apico. One isolate had Type III alleles at all loci except Type II alleles at SAG2 and Apico. Two sea otter isolates had a mixed infection. Twenty-one (54%) isolates had an unique allele at SAG1 locus. Further genotyping or DNA sequence analysis for 18 of these 21 isolates at loci SAG1 and GRA6 revealed that there were two different genotypes, including the previously identified Type X (four isolates) and a new genotype named Type A (14 isolates). The results from this study suggest that the sea otter isolates are genetically diverse.  相似文献   

20.
为了更好地了解盘羊及其杂交后代(盘羊♂×欧拉羊♀)的遗传信息,为盘羊遗传资源评价及欧拉羊的复壮改良提供理论依据。本试验选取24对微卫星引物,应用PCR扩增和毛细管电泳的方法对24只盘羊和24只杂交羊个体进行遗传多样性分析。结果显示,在24只盘羊中,24个微卫星位点上共检测到167个等位基因,平均等位基因数目为6.9583,平均有效等位基因数为3.3665,平均观测杂合度为0.4497,平均期望杂合度为0.6779,平均多态信息含量为0.6265,其中,等位基因数目最多的是位点MAF70,有效等位基因数目、期望杂合度、多态信息含量最高的是位点OarFCB193,观测杂合度最高的是位点ILSTS11;在24只杂交羊中,24个微卫星位点上共检测到154个等位基因,平均等位基因数目为6.4166,平均有效等位基因数为3.4061,平均观测杂合度为0.4566,平均期望杂合度为0.6751,平均多态信息含量为0.6265,其中,等位基因数目、有效等位基因数目、期望杂合度、多态信息含量最高的是位点MAF70,观测杂合度最高的是位点OarJMP58。从遗传学角度得出,盘羊和杂交羊遗传指标结果相近,试验所得数据可用于盘羊遗传资源评价及欧拉羊的复壮改良。  相似文献   

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