Perspectives of a scrapie resistance breeding scheme targeting Q211, S146 and K222 caprine PRNP alleles in Greek goats.
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ABSTRACT:
SUBMITTER: Kanata E
PROVIDER: S-EPMC4030296 | biostudies-literature | 2014 Apr
REPOSITORIES: biostudies-literature
Publications
Perspectives of a scrapie resistance breeding scheme targeting Q211, S146 and K222 caprine PRNP alleles in Greek goats.
Kanata Eirini E Humphreys-Panagiotidis Cynthia C Giadinis Nektarios D ND Papaioannou Nikolaos N Arsenakis Minas M Sklaviadis Theodoros T
Veterinary research 20140409
The present study investigates the potential use of the scrapie-protective Q211 S146 and K222 caprine PRNP alleles as targets for selective breeding in Greek goats. Genotyping data from a high number of healthy goats with special emphasis on bucks, revealed high frequencies of these alleles, while the estimated probabilities of disease occurrence in animals carrying these alleles were low, suggesting that they can be used for selection. Greek goats represent one of the largest populations in Eur ...[more]
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Project description:The European Union has implemented breeding programmes to increase scrapie resistance in sheep. A similar approach can be applied also in goats since the K222 allele provides a level of resistance equivalent to that of ARR in sheep. The European Food Safety Authority stated that breeding for resistance could be offered as an option for Member States to control classical scrapie in goats. We assessed the impact of different breeding strategies on PRNP genotype frequencies using a mathematical model that describes in detail the evolution of K222 in two goat breeds, Chamois Coloured and Saanen. Different patterns of age structure and replacement rate were modelled as factors affecting response to selection. Breeding for scrapie resistance can be implemented in goats, even though the initial K222 frequencies in these breeds are not particularly favourable and the rate at which the resistant animals increase, both breeding and slaughtered for meat production, is slow. If the goal is not to achieve the fixation of resistance allele, it is advisable to carry out selection only until a desired frequency of K222-carriers has been attained. Nucleus selection vs. selection on the overall populations is less expensive but takes longer to reach the desired output. The programme performed on the two goat breeds serves as a model of the response the selection could have in other breeds that show different initial frequencies and population structure. In this respect, the model has a general applicability.
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Project description:Small ruminants, including sheep and goats are natural hosts of scrapie, and the progression of scrapie pathogenesis is strongly influenced by polymorphisms in the prion protein gene (PRNP). Although Korean native goats have been consumed as meat and health food, the evaluation of the susceptibility to scrapie in these goats has not been performed thus far. Therefore, we investigated the genotype and allele frequencies of PRNP polymorphisms in 211 Korean native goats and compared them with those in scrapie-affected animals from previous studies. We found a total of 12 single nucleotide polymorphisms (SNPs) including 10 nonsynonymous and 2 synonymous SNPs in Korean native goats. Significant differences in allele frequencies of PRNP codons 143 and 146 were found between scrapie-affected goats and Korean native goats (p?<?0.01). By contrast, in PRNP codons 168, 211 and 222, there were no significant differences in the genotype and allele frequencies between scrapie-affected animals and Korean native goats. To evaluate structural changes caused by nonsynonymous SNPs, PolyPhen-2, PROVEAN and AMYCO analyses were performed. PolyPhen-2 predicted "possibly damaging" for W102G and R154H, "probably damaging" for G127S. AMYCO predicted relatively low for amyloid propensity of prion protein in Korean native black goats. This is the first study to evaluate the scrapie sensitivity and the first in silico evaluation of nonsynonymous SNPs in Korean native black goats.
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Project description:Polymorphisms at PRNP gene locus have been associated with resistance against classical scrapie in goats. Genetic selection on this gene within appropriate breeding programs may contribute to the control of the disease. The present study characterized the genetic profile of codons 146, 211 and 222 in three dairy goat breeds in Greece. A total of 766 dairy goats from seven farms were used. Animals belonged to two indigenous Greek, Eghoria (n = 264) and Skopelos (n = 287) and a foreign breed, Damascus (n = 215). Genomic DNA was extracted from blood samples from individual animals. Polymorphisms were detected in these codons using Real-Time PCR analysis and four different Custom TaqMan® SNP Genotyping Assays. Genotypic, allelic and haplotypic frequencies were calculated based on individual animal genotypes. Chi-square tests were used to examine Hardy-Weinberg equilibrium state and compare genotypic distribution across breeds. Genetic distances among the three breeds, and between these and 30 breeds reared in other countries were estimated based on haplotypic frequencies using fixation index FST with Arlequin v3.1 software; a Neighbor-Joining tree was created using PHYLIP package v3.695. Level of statistical significance was set at P = 0.01. All scrapie resistance-associated alleles (146S, 146D, 211Q and 222K) were detected in the studied population. Significant frequency differences were observed between the indigenous Greek and Damascus breeds. Alleles 222K and 146S had the highest frequency in the two indigenous and the Damascus breed, respectively (ca. 6.0%). The studied breeds shared similar haplotypic frequencies with most South Italian and Turkish breeds but differed significantly from North-Western European, Far East and some USA goat breeds. Results suggest there is adequate variation in the PRNP gene locus to support breeding programs for enhanced scrapie resistance in goats reared in Greece. Genetic comparisons among goat breeds indicate that separate breeding programs should apply to the two indigenous and the imported Damascus breeds.
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Project description:Prion diseases are progressive and fatal, neurodegenerative disorders described in humans and animals. According to the "protein-only" hypothesis, the normal host-encoded prion protein (PrPC) is converted into a pathological and infectious form (PrPSc) in these diseases. Transgenic knockout models have shown that PrPC is a prerequisite for the development of prion disease. In Norwegian dairy goats, a mutation (Ter) in the prion protein gene (PRNP) effectively blocks PrPC synthesis. We inoculated 12 goats (4 PRNP+/+, 4 PRNP+/Ter, and 4 PRNPTer/Ter) intracerebrally with goat scrapie prions. The mean incubation time until clinical signs of prion disease was 601 days post-inoculation (dpi) in PRNP+/+ goats and 773 dpi in PRNP+/Ter goats. PrPSc and vacuolation were similarly distributed in the central nervous system (CNS) of both groups and observed in all brain regions and segments of the spinal cord. Generally, accumulation of PrPSc was limited in peripheral organs, but all PRNP+/+ goats and 1 of 4 PRNP+/Ter goats were positive in head lymph nodes. The four PRNPTer/Ter goats remained healthy, without clinical signs of prion disease, and were euthanized 1260 dpi. As expected, no accumulation of PrPSc was observed in the CNS or peripheral tissues of this group, as assessed by immunohistochemistry, enzyme immunoassay, and real-time quaking-induced conversion. Our study shows for the first time that animals devoid of PrPC due to a natural mutation do not propagate prions and are resistant to scrapie. Clinical onset of disease is delayed in heterozygous goats expressing about 50% of PrPC levels.
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Project description:Goats (Capra hircus) were domesticated during the late Neolithic, approximately 10,500 years ago, and humans exerted minor selection pressure until fairly recently. Probably the largest genetic change occurring over the millennia happened via natural selection and random genetic drift, the latter causing genes to be fixed in small and isolated populations. Recent human-influenced genetic changes have occurred through biometrics and genomics. For the most part, biometrics has concentrated upon the refining of estimates of heritabilities and genetic correlations. Heritabilities are instrumental in the calculation of estimated breeding values and genetic correlations are necessary in the construction of selection indices that account for changes in multiple traits under selection at one time. Early genomic studies focused upon microsatellite markers, which are short tandem repeats of nucleic acids and which are detected using polymerase chain reaction primers flanking the microsatellite. Microsatellite markers have been very important in parentage verification, which can impact genetic progress. Additionally, microsatellite markers have been a useful tool in assessing genetic diversity between and among breeds, which is important in the conservation of minor breeds. Single nucleotide polymorphisms are a new genomic tool that have refined classical BLUP methodology (biometric) to provide more accurate genomic estimated breeding values, provided a large reference population is available.
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