Prion protein genotype survey confirms low frequency of scrapie‐resistant K222 allele in British goat herds

Goldmann, Wilfred; Marier, E.; Stewart, Paula; Konold, Timm; Street, Samantha; Langeveld, J.P.M.; Windl, Otto; Ortiz-Pelaez, Angel

doi:10.1136/vr.103521

Cited by 26 publications

(31 citation statements)

References 23 publications

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“…Both in Great Britain (Goldmann et al . ) and USA (White et al . ), PRNP frequencies have been determined in the Toggenburger, but their frequencies are much lower (Table ).…”

Section: Discussionmentioning

confidence: 99%

Variation in the prion protein sequence in Dutch goat breeds

Windig

Hoving

Priem

et al. 2016

J Animal Breeding Genetics

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Scrapie is a neurodegenerative disease occurring in goats and sheep. Several haplotypes of the prion protein increase resistance to scrapie infection and may be used in selective breeding to help eradicate scrapie. In this study, frequencies of the allelic variants of the PrP gene are determined for six goat breeds in the Netherlands. Overall frequencies in Dutch goats were determined from 768 brain tissue samples in 2005, 766 in 2008 and 300 in 2012, derived from random sampling for the national scrapie surveillance without knowledge of the breed. Breed specific frequencies were determined in the winter 2013/2014 by sampling 300 breeding animals from the main breeders of the different breeds. Detailed analysis of the scrapie-resistant K222 haplotype was carried out in 2014 for 220 Dutch Toggenburger goats and in 2015 for 942 goats from the Saanen derived White Goat breed. Nine haplotypes were identified in the Dutch breeds. Frequencies for non-wild type haplotypes were generally low. Exception was the K222 haplotype in the Dutch Toggenburger (29%) and the S146 haplotype in the Nubian and Boer breeds (respectively 7 and 31%). The frequency of the K222 haplotype in the Toggenburger was higher than for any other breed reported in literature, while for the White Goat breed it was with 3.1% similar to frequencies of other Saanen or Saanen derived breeds. Further evidence was found for the existence of two M142 haplotypes, M142 /S240 and M142 /P240 . Breeds vary in haplotype frequencies but frequencies of resistant genotypes are generally low and consequently selective breeding for scrapie resistance can only be slow but will benefit from animals identified in this study. The unexpectedly high frequency of the K222 haplotype in the Dutch Toggenburger underlines the need for conservation of rare breeds in order to conserve genetic diversity rare or absent in other breeds.

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“…Both in Great Britain (Goldmann et al . ) and USA (White et al . ), PRNP frequencies have been determined in the Toggenburger, but their frequencies are much lower (Table ).…”

Section: Discussionmentioning

confidence: 99%

Variation in the prion protein sequence in Dutch goat breeds

Windig

Hoving

Priem

et al. 2016

J Animal Breeding Genetics

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“…According to Hardy–Weinberg equilibrium calculations, homozygotes for one rare allele (< 5%) will have a frequency of less than 0.3%, while heterozygotes for two rare alleles will have a frequency of less than 0.5%. The published surveys with full genotype information confirm the expected low frequencies: all homozygotes (excluding wild‐type alleles) were 0.48% and all double heterozygotes (no wild‐type alleles) were 0.43% (based on a total of almost 2600 genotypes) (Billinis et al., ; Acutis et al., ; Vaccari et al., ; Papasavva‐Stylianou et al., ; Bouzalas et al., ; Fragkiadaki et al., ; Goldmann et al., , ; Papasavva‐Stylianou et al., ; Maestrale et al., ; Acín et al., Corbière et al., ; Barillet et al., ). Despite the overall problem with assigning resistance to rare homozygotes due to their observed frequencies, a protective phenotype has been described for MM142 homozygotes similar to IM142 heterozygotes (Table ) (González et al., ; Goldmann et al., ) and also for SS146 and DD146 homozygotes compared to NS146 and ND146 heterozygotes (Georgiadou et al., ).…”

Section: Assessmentmentioning

confidence: 75%

Genetic resistance to transmissible spongiform encephalopathies (TSE) in goats

Ricci¹,

Allende²,

Bolton³

et al. 2017

EFS2

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Breeding programmes to promote resistance to classical scrapie, similar to those for sheep in existing transmissible spongiform encephalopathies (TSE) regulations, have not been established in goats. The European Commission requested a scientific opinion from EFSA on the current knowledge of genetic resistance to TSE in goats. An evaluation tool, which considers both the weight of evidence and strength of resistance to classical scrapie of alleles in the goat PRNP gene, was developed and applied to nine selected alleles of interest. Using the tool, the quality and certainty of the field and experimental data are considered robust enough to conclude that the K222, D146 and S146 alleles both confer genetic resistance against classical scrapie strains known to occur naturally in the EU goat population, with which they have been challenged both experimentally and under field conditions. The weight of evidence for K222 is greater than that currently available for the D146 and S146 alleles and for the ARR allele in sheep in 2001. Breeding for resistance can be an effective tool for controlling classical scrapie in goats and it could be an option available to member states, both at herd and population levels. There is insufficient evidence to assess the impact of K222, D146 and S146 alleles on susceptibility to atypical scrapie and bovine spongiform encephalopathy (BSE), or on health and production traits. These alleles are heterogeneously distributed across the EU Member States and goat breeds, but often at low frequencies (< 10%). Given these low frequencies, high selection pressure may have an adverse effect on genetic diversity so any breeding for resistance programmes should be developed at Member States, rather than EU level and their impact monitored, with particular attention to the potential for any negative impact in rare or small population breeds.

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“…It is also important to understand the prevalence of K222 allele in the world, at least in the United States is observed a low K222 frequency in goats. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats, it confirms low frequency of scrapie-resistant K222 allele in British goat herds (Goldmann et al, 2016). A high variability in the caprine prion protein gene in Northern and Southern Italian breeds (13-point mutations) were identified (Acutis et al, 2007).…”

Section: Role Of Prnp In Small Ruminantsmentioning

confidence: 88%

Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease

Curcio

Sebastiani

Lorenzo

et al. 2016

Animal

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Scrapie is a naturally occurring transmissible spongiform encephalopathy in sheep and goat. It has been known for~250 years and is characterised by the accumulation of an abnormal isoform of a host-encoded prion protein that leads to progressive neurodegeneration and death. Scrapie is recognised in two forms, classical and atypical scrapie. The susceptibility to both types of scrapie is influenced by polymorphisms of the prion protein gene (PRNP). Sheep susceptibility or resistance to classical scrapie is strongly regulated by the polymorphisms at codons 136, 154 and 171 of the PRNP. The genetic role in atypical scrapie in sheep has been defined by polymorphisms at codons 141, 154 and 171, which are associated with different degrees of risk in the occurrence of the ovine disease. Progress has been achieved in the prevention of scrapie in sheep due to efficient genetic breeding programmes based on eradication and control of the disease. In Europe, the success of these programmes has been verified by applying eradication and genetic selection plans. In general terms, the ovine selection plans aim to eliminate and reduce the susceptible allele and to enrich the resistant allele ARR. During outbreaks all susceptible animals are slaughtered, only ARR/ARR resistant rams and sheep and semi-resistant females are preserved. In the occurrence of scrapie positive goats a complete cull of the flock (stamping out) is performed with great economic loss and severe risk of extinction for the endangered breeds. The ability to select scrapie-resistant animals allows to define new breeding strategies aimed to boost genetic progress while reducing costs during scrapie outbreaks. Allelic variants of PRNP can be protective for caprine scrapie, and the knowledge of their distribution in goats has become very important. Over the past few years, the integration of genetic information on goat populations could be used to make selection decisions, commonly referred to as genetic selection. The objective of this review was to summarise the main findings of polymorphisms of the caprine prion protein (PrP) gene and to discuss the possible application of goat breeding schemes integrating genetic selection, with their relative advantages and limitations.

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Prion protein genotype survey confirms low frequency of scrapie‐resistant K222 allele in British goat herds

Cited by 26 publications

References 23 publications

Variation in the prion protein sequence in Dutch goat breeds

Variation in the prion protein sequence in Dutch goat breeds

Genetic resistance to transmissible spongiform encephalopathies (TSE) in goats

Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease

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