Breeding German sheep for resistance to scrapie

Susceptibility to clinical scrapie is associated with polymorphisms in the prion protein (PrP) gene. The ARR allele reduces susceptibility to clinical disease caused by all known strains of the transmissible spongiform encephalopathy (TSE) agents. For the economically important German breeds of sheep the PrP allele frequencies are well known, but this paper presents representative genotyping results for 1526 sheep from two smaller milk sheep breeds and 2446 sheep from 14 mostly indigenous land sheep breeds. The ARR allele was detected in each breed but the breed-specific ARR frequencies varied between 1 and 63 per cent. In small populations with a very low ARR frequency the ARR allele could be lost by genetic drift. A simulation study was therefore made to examine the effects of different breeding schemes in populations of different sizes on attempts to select for the ARR allele in an endangered population. In breeds in which no homozygous rams are available the breeding strategy would depend on the number of heterozygous rams, and the genotyping and selection of suitable breeding ewes would reduce the time required to achieve a highly resistant population. In general, in all the breeds a selection programme to achieve 99 per cent ARR homozygous genotypes would be feasible in six to nine generations, depending on the initial allele frequencies. In small populations the inbreeding rate may increase if no specific mating plans are developed by the breeding organisations.     

Genetic variability following selection for scrapie resistance in six autochthonous sheep breeds in the province of Bolzano (northern Italy)

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.     

PrP genotype frequencies of Quebec sheep breeds determined by real-time PCR and molecular beacons

The allele and genotype frequencies of the prion protein gene (PrP), known to have an impact on scrapie susceptibility, were determined by real-time PCR for 500 Quebec purebred rams. Molecular beacons were very efficient in discriminating the 5 alleles investigated. Polymorphisms at coding positions 136, 154, and 171 of the PrP gene were analyzed using 3 separate real-time PCR reactions and a total of 7 molecular beacons. A total of 4 different alleles (ARQ, ARR, AHR, and VRQ) were observed at different frequencies among the 7 breeds of sheep investigated. Results show that more than 50% of the rams in every breed carried at least one ARR allele, which is considered the most resistant to scrapie. The susceptibility ARQ allele was also present in every breed and together with the ARR allele, they were the most frequent alleles found in Quebec rams. The VRQ allele associated with the highest susceptibility to scrapie occurred in 5 of the 7 breeds, although at low frequencies. Overall, the results indicate that the frequencies of PrP alleles and genotypes in common breeds of sheep in Quebec make it feasible to reduce scrapie risk by selective breeding.     

Effects of different selection strategies on breeding towards scrapie resistance in the German Grey-horned Heath population

Scrapie resistance is related to polymorphisms of the prion protein (PrP) gene. The homozygous ARR/ARR genotype of the prion protein gene is associated with high resistance against conventional scrapie infections. But this can lead to a distinct loss of genetic variation in breeds with a small population size or a low frequency of the ARR allele. For these populations an optimal breeding scheme for breeding towards scrapie resistance and an arbitrarily chosen production trait with conservation of the genetic diversity is not known yet. A simulation programme was developed, in which the structures of local populations could be used as input parameters, and the development of the ARR allele frequency, of the inbreeding coefficient, of a production trait and the genetic drift were computed in dependence of different selection schemes for scrapie resistance. An optimal strategy for the German Grey Heath population from Lower Saxony should be found. An optimal strategy in a breeding programme for ARR homozygosis should also maintain the genetic diversity present in a breed. This could be achieved when initially ARR heterozygous sheep were bred until a certain threshold value of the ARR allele was reached. The speed and costs of the breeding progress towards fixation of the ARR allele should then be optimized with regard to the aims of the breeders and breeding organisations, whereas a faster breeding towards scrapie resistance goes along with higher genotyping costs and vice versa.     

A genealogical survey of Australian registered dog breeds

Breeding practices were analysed for 32 registered dog breeds representing very small registries (120 Central Asian shepherd dogs) through to very large registries (252,521 German shepherd dogs) in Australia. The vast majority (91%) of registered kennels in Australia that were sampled did not regularly employ either close breeding or popular sire usage in their kennels and the weighted mean inbreeding coefficient of Australian pedigree dogs was <5%. Australian breed mean inbreeding coefficients ranged from 0% (Central Asian shepherd dog) to 10.1% (Bichon Frise). Breed effective population sizes ranged from 26 (Ibizan hound) to 1090 (Golden retriever), comparable with other species of domesticated animals. The relatively low levels of inbreeding suggest that pedigree dog disorders are unlikely to arise frequently from the use of popular sires or close breeding in Australian registered dog breeds. It is possible that deleterious allele fixation might be driven by founder effects, genetic drift or adverse selection practices, which were not assessed in this analysis. European popular sire definitions should be revisited for rare breeds.     

PrP genotype frequencies in German breeding sheep and the potential to breed for resistance to scrapie

Genetic susceptibility to scrapie is associated with polymorphisms in three different codons of the ovine prion protein (PrP) gene (136, 154, 171). Studies of PrP genotypes linked to scrapie have revealed the resistance of homozygous PrPARR/PrPARR animals and the high risk of PrPVRQ/PrPVRQ and PrPvRQ/PrPARQ animals in scrapie-affected flocks. The selection of PrPARR/PrPARR genotypes may therefore provide a strategy for controlling clinical scrapie. The genotypes of 1361 German breeding sheep from 15 different breeds in northern Germany were determined. Apart from the wildtype allele PrPARQ, at least four mutually exclusive allelic variants were found. The greatest variability within the PrP gene was encountered in texel sheep, in which 14 PrP genotypes were found. In the important meat breeds, Suffolk, German whiteheaded mutton and German blackheaded mutton, the PrPARR allele was predominant, and in these breeds the breeding of scrapie-resistant pedigree flocks within four generations seems to be a feasible option. In the texel sheep, the German merino, the German milk and the German land sheep breeds, the frequency of the PrPARR allele was much lower, and in several breeds no homozygous rams were available for breeding purposes. In these breeds the breeding strategy would depend on the number of heterozygous rams available, but resistant pedigree flocks could be achieved within nine generations.     

Evidence for a breed specific association between PrP genotype and ultrasonic muscle depth but not for survivability, growth or carcass traits in sheep

The ARR allele of the prion protein gene is associated with resistance to classical scrapie, while the ARQ allele is associated with susceptibility. The objective of this study was to estimate the effect, on lamb growth and carcass traits, of replacing an ARQ allele with an ARR allele. Pedigree rams (22 Suffolks, 18 Texels and 18 Charollais) were sourced in pairs, from the same flock (by the same sire where possible), with one member being ARR/ARR and the other being ARQ/ARQ and these rams were progeny tested through single-sire mating in six flocks. Effects of ram genotype on reproductive performance of ewes and on growth and carcass traits of progeny were estimated using mixed model procedures with sire as a random effect. Ram genotype had no effect on litter size at birth or on lamb survival as measured by the number of lambs reared. The differences between the performance of progeny by ARR/ARR and ARQ/ARQ sires provided an estimate of the effect of substituting an ARR allele for an ARQ allele. This allele substitution had no effect on birth weight, growth rate, weight at 5 or 14 weeks, weight or ultrasonic fat depth at 120 days of age or on carcass classification traits (conformation, fatness) for the Suffolk, Texel or Charollais breeds. Substituting an ARR allele for an ARQ allele had a negative effect on ultrasonic muscle depth at 120 days for the progeny of Suffolk rams (P = 0.01) but had a positive effect on ultrasonic muscle depth at 120 days for the progeny of Charollais rams (P = 0.02). The ARR substitution effect was negative for slaughter age in the Suffolk (P < 0.05) and positive for carcass weight in Texel progeny (P < 0.05). The magnitude of these effects was quite small, however, and the overall results support the hypothesis that substituting an ARR allele for an ARQ allele has no important negative effect on lamb growth or carcass traits in any of the breeds examined.     

Genetic management of Dutch golden retriever dogs with a simulation tool

Excessive inbreeding rates and small effective population sizes are an important problem in many populations of dogs. Proper genetic management of these populations can decrease the problem, and several measures are available. However, the effectiveness of these measures is not clear beforehand. Therefore, a simulation model was developed to test measures that aim to decrease the rate of inbreeding. The simulation program was used to evaluate inbreeding restriction measures in the Dutch golden retriever dog population. This population consisted of approximately 600 dams and 150 sires that produce 300 litters each year. The five most popular sires sire approximately 25% of the litters in a year. Simulations show that the small number of popular sires and their high contribution to the next generation are the main determinants of the inbreeding rates. Restricting breeding to animals with a low average relatedness to all other animals in the population was the most effective measure and decreased the rate of inbreeding per generation from 0.41 to 0.12%. Minimizing co‐ancestry of parents was not effective in the long run, but decreased variation in inbreeding rates. Restricting the number of litters per sire generally decreased the generation interval because sires were replaced more quickly, once they met their restriction. In some instances, this lead to an increase in inbreeding rates because the next generations were more related. The simulation tool proved to be a powerful and educational tool for deciding which breeding restrictions to apply, and can be effective in different breeds and species as well.     

Genetic diversity loss due to selection for scrapie resistance in the rare Spanish Xalda sheep breed

The effect of selection for scrapie resistance on genetic variability in the rare Xalda sheep breed was studied. Pedigree information comprised 1851 animals (1444 alive) at the moment of sampling. A total of 304 reproductive (or selected for reproduction) Xalda individuals were sampled and genotyped for 14 microsatellites. Genetic variability was assessed using: gene diversity (1 − average kinship, GD), mean average relatedness (AR) and self-coancestry (c_i) at the genealogical level; and expected heterozygosity (H_e), molecular mean kinship (Mk), molecular self-coancestry (s_i) and rarefacted average number of alleles per locus (A) at the molecular level. Two breeding strategies were evaluated: a) use of only young rams with genotype ARR/ARR and young ewes with low to moderate risk (risk groups R1 to R3); b) breeding without selection for PrP genotypes. The major cause of losses of genetic variability in the Xalda breed is the drift that occurs when a new group of reproductive individuals is selected. The loss of genetic variability is small in females compared to the males, where it is considerable. However, losses at the molecular level for young females with respect to adult females were above 5%. Young male individuals also retained most of the genetic variability assessed in adult rams. Selection against susceptibility to scrapie produced additional losses of more than 2% for H_e and A when rYF individuals are considered. As regards males, the situation becomes critical because of the scant number of available ARR/ARR young rams. The consequences for the management of the Xalda breed are discussed.     

Reducing inbreeding rates with a breeding circle: Theory and practice in Veluws Heideschaap

Breeding circles allow genetic management in closed populations without pedigrees. In a breeding circle, breeding is split over sub‐populations. Each sub‐population receives breeding males from a single sub‐population and supplies breeding males to one other sub‐population. Donor‐recipient combinations of sub‐populations remain the same over time. Here, we derive inbreeding levels both mathematically and by computer simulation and compare them to actual inbreeding rates derived from DNA information in a real sheep population. In Veluws Heideschaap, a breeding circle has been in operation for over 30 years. Mathematically, starting with inbreeding levels and kinships set to zero, inbreeding rates per generation (ΔF) initially were 0.29%–0.47% within flocks but later converged to 0.18% in all flocks. When, more realistically, inbreeding levels at the start were high and kinship between flocks low, inbreeding levels immediately dropped to the kinship levels between flocks and rates more gradually converged to 0.18%. In computer simulations with overlapping generations, inbreeding levels and rates followed the same pattern, but converged to a lower ΔF of 0.12%. ΔF was determined in the real population with a 12 K SNP chip in recent generations. ΔF in the real population was 0.29%, based on markers to 0.41% per generation based on heterozygosity levels. This is two to three times the theoretically derived values. These increased rates in the real population are probably due to selection and/or the presence of dominant rams siring a disproportionate number of offspring. When these were simulated, ΔF agreed better: 0.35% for selection, 0.38% for dominant rams and 0.67% for both together. The realized inbreeding rates are a warning that in a real population inbreeding rates in a breeding circle can be higher than theoretically expected due to selection and dominant rams. Without a breeding circle, however, inbreeding rates would have been even higher.     

Merino sheep breed's genetic resistance to scrapie: genetic structure and comparison of five eradication strategies

Three thousand one hundred and ninety-three Merino-breeding males were genotyped for Scrapie-resistance gene. They showed a high frequency of ARQ allele while VRQ allele frequency, linked to the highest susceptibility, was close to 0. Alleles linked to Scrapie-susceptibility frequencies have been studied in different Merino flocks. Most of the variability is intraflock, not interflock. In addition, there is an excess of heterozygotes due to crossbreeding or Wahlund effect.

Five control and prevention strategies were studied: first genotyping males and females and eliminating VRQ carriers and ARQ/ARQ rams; second genotyping males and females and eliminating VRQ carriers; third genotyping males and eliminating VRQ carriers and ARQ/ARQ rams; fourth genotyping males and using only as breeders ARR/ARR, ARR/AHQ, AHQ/AHQ and ARQ/ARQ rams; fifth genotyping males and using only as breeders ARR/ARR, ARR/AHQ and AHQ/AHQ rams. They were simulated from allelic and genotypic frequencies to decide which animals had to be genotyped and which animals had to be eliminated due to their genotypes and risk levels. The third option, to genotype rams and to eliminate ARQ/ARQ and VRQ carriers, would be the best strategy to improve the resistance and would cause minimal cost and loss of animals.     

Assessing the efficacy of a ram-genotyping programme to reduce susceptibility to scrapie in Great Britain

Susceptibility to clinical scrapie is associated with polymorphisms in the PrP gene. The 'ARR' allele of this gene reduces susceptibility to clinical disease caused by all known strains of the transmissible spongiform encephalopathy (TSE) agent. The British government proposes to use a ram-genotyping scheme to breed genetic resistance to clinical scrapie into the national sheep population. We considered how best to target limited genotyping resources to achieve the maximum rate of genotype evolution. We created a metapopulation model of the British sheep industry, which includes the major pure-breeds of sheep and the cross-breeds produced by crossing these pure-bred animals. The main criterion for assessing the efficacy of different strategies was the time taken to increase the prevalence of the ARR allele in the slaughter-lamb population. Our model predicted that the most-effective strategy would be to target genotyping to those rams used for pure-breeding (i.e. mated with the same breed of ewe). This strategy was compared to two further strategies, in which the proportion of rams genotyped in each breed depended on the prevalence of the ARR/ARR genotype in that breed. A policy in which the proportion of animals genotyped is reduced as the ARR prevalence in that breed increases is efficient. The most-effective policy was targeting the hill sector in the early years and gradually switching to genotyping more terminal-sire and longwool rams as the resistance of the hill sector increases.     

Inbreeding in populations with incomplete pedigrees

Inbreeding has detrimental effects on a number of economically important traits. W iggans et al. (1995) estimated inbreeding depression of ?29 kg, ?1.08 kg and ?0.97 kg for each 1% increase of inbreeding for the traits milk, fat and protein yield, respectively, across several dairy cattle breeds. For post-weaning gain in Hereford cattle, the depression was ?0.24 kg (G engler et al. 1998). For the number of piglets born alive, 21-day litter weight, and days to 104.5 kg, it was ?0.023, ?0.052 and 0.21, respectively (C ulbertson et al. 1998). Inbreeding also adversely impacts reproductive traits, such as delayed puberty, reduced conception rates, higher likelihood of losing established pregnancies, increased mortality of calves and lowered bull fertility (Y oung et al. 1969). National genetic evaluations involve animals with incomplete pedigrees. Regular inbreeding algorithms (RA) based on the definition of W right (1922), such as those by Q uaas (1976), calculate the inbreeding of animals with at least one parent missing as zero. Even if an animal has both parents known, its inbreeding will be underestimated if some of its ancestors are unidentified. If the proportion of missing parents is large, the inbreeding trend in a population could be seriously underestimated. Subsequently, losses from inbreeding would be underestimated, and steps to slow the increase of inbreeding, such as using sires that are less related to the general population or mating less-related animals (T oro and P erez -E nciso , 1990; G rundy et al. 1994; M euwissen and S onneson 1998; V an R aden and S mith 1999), may be delayed. In particular, use of a mating system can result in matings adjusted for both inbreeding and dominance (M isztal et al. 1999). In populations that use AI substantially, unidentified parents may not differ genetically from identified parents, on average. Therefore the real average inbreeding in animals with unidentified parent(s) may be similar to their contemporaries with both parents known. V an R aden (1992) proposed an algorithm (VRA), where the inbreeding of animals whose parent(s) are unknown is equal to the mean inbreeding of their contemporaries with known parents. Contemporaries are stratified along unknown parent groups (UPG). VRA has been applied to a few US dairy breeds (V an R aden 1992; W iggans et al. 1995). The calculated inbreeding for the youngest Holstein animals was 3.7% with RA and increased to 4.2% with VRA (V an R aden 1992). The increase was small because the number of unidentified animals was small. However, the performance of VRA in recovering inbreeding lost for a range of incomplete pedigrees has not been evaluated. The objectives of this study were (i) to determine average inbreeding coefficients when pedigrees are increasingly more incomplete; (ii) to assess the efficacy of VRA in recovering these inbreeding coefficients; and (iii) to determine the mean inbreeding using the two inbreeding algorithms in a large beef population.     

Effect of selection for scrapie resistance on genetic diversity in a rare and locally adapted sheep breed: The case of Sambucana

In Italy, since 2005 a breeding plan to increase scrapie resistance has been adopted. The impact of this selection on genetic diversity was assessed on Sambucana, an autochtonous sheep breed reared in southern Piedmont, by analysing the evolution of allele frequencies at different levels: PRNP (prion protein) gene, microsatellite loci on OAR13 (where PRNR maps), and microsatellite loci on other chromosomes, not subjected to selection for scrapie resistance. A total of 147 young rams, 80 born in 2004 and 67 in 2008–2009 were analysed. Evidence of diversity loss was observed for PRNP gene as a consequence of the directional selection. Diversity was affected in the immediate vicinity of PRNP but the effect on more distant loci on the same chromosome was trivial. With regard to neutral markers, lack of heterozygosis with no changeover of allele frequencies was observed suggesting an increase of inbreeding. Mating policies would be sufficient to solve these problems. A selection scheme based on genotyping rams and eliminating carriers of both susceptible and high susceptible alleles is the best way to improve natural resistance to scrapie with low costs and minimal problems in the current conservation programmes targeting rare breeds.     

Prion protein genetic polymorphisms and breeding strategies in Portuguese breeds of sheep

Polymorphisms at the prion protein locus were studied in 965 animals, representative of 13 native and 3 exotic sheep breeds in Portugal. In general, ARQ was the predominant allele in most breeds, but the desirable ARR allele was present in all breeds studied. A different pattern was found in Ile de France, where ARR was predominant and VRQ had the highest frequency among the breeds analysed. In most of the breeds, especially in those of the coarse-wool type, the major hurdle in selecting for genetic resistance to clinical scrapie was the elimination of ARQ rather than VRQ alleles. Breeding schemes aiming at the creation of ARR-homozygous selection nuclei were simulated for representative breeds, and results indicate that, with intense selection, it would take between 4 years in Ile de France and 11 years in Mondegueira to obtain homozygosity in the nucleus, and the length of time needed for fixation was not affected by the type of mating (random or assortative) used. Nevertheless, intense selection for the PrP genotype alone would have undesirable consequences in terms of inbreeding, and correlated responses in production and adaptation traits should be evaluated before such a scheme is adopted.     

There is room for selection in a small local pig breed when using optimum contribution selection: a simulation study

Selection progress must be carefully balanced against the conservation of genetic variation in small populations of local breeds. Well-defined breeding programs?with specified selection traits are rare in local pig breeds. Given the small population size,?the focus is often on the management of genetic diversity. However, in local breeds, optimum contribution selection can be applied to control the rate of inbreeding and to avoid reduced performance in traits with high market value. The aim of this study was to assess the extent to which a breeding program aiming for improved product quality in a small local breed would be feasible. We used stochastic simulations to compare 25 scenarios. The scenarios differed in?size of population, selection intensity of boars, type of selection (random selection, truncation selection based on BLUP breeding values, or optimum contribution selection based on BLUP breeding values), and heritability of?the selection trait. It was assumed that the local breed is used in an extensive system for a high-meat-quality market.?The?simulations showed that in the smallest population (300 female reproducers), inbreeding increased by 0.8% when selection was performed at random. With optimum contribution selection, genetic progress can be achieved that is almost as great as that with truncation selection based on BLUP breeding values (0.2 to 0.5 vs. 0.3 to 0.5 genetic SD, P < 0.05), but at a considerably decreased rate of inbreeding (0.7 to 1.2 vs. 2.3 to 5.7%, P < 0.01). This confirmation of the potential utilization of OCS even in small populations is important in the context of sustainable management and the use of animal genetic resources.     

Frequencies of PrP genotypes in 38 breeds of sheep sampled in the National Scrapie Plan for Great Britain

Between October 2001 and January 2003 the prion protein (PrP) genotypes of over 250,000 sheep were determined through the operation of the National Scrapie Plan (NSP); the results for 38 breeds were analysed to provide an estimate of the underlying PrP genotype distribution of the British sheep population. Although there was marked variability among the genotype profiles of the different breeds, several trends emerged. A comparison of the allele frequencies demonstrated that the breeds could be grouped into three categories: breeds dominated by ARR and ARQ in which the frequency of ARR exceeded the frequency of ARQ; breeds dominated by ARR and ARQ in which the frequency of ARQ exceeded the frequency of ARR; and breeds with significant levels of either AHQ, ARH or VRQ. Hill breeds were more likely to have a lower proportion of animals at low risk of scrapie (NSP type 1) and a higher proportion of animals at an intermediate risk of scrapie (NSP type 3) than other breeds. Most breeds had a small proportion of animals at high risk of scrapie (NSP type 5). The frequency of ARR/VRQ (NSP type 4) was variable.     

Indigenous sheep breeds of North Ethiopia: characterization of their phenotype and major production system

A study was conducted in Tigrai, Northern Ethiopia to describe the sheep breeds and their production system. The survey was done in selected districts known for their high sheep population density. The phenotype characterization identified distinct features for each breed. The breeds are Aberegelle, Ille, Begait, and the common Tigrai highland sheep. The strong discriminating phenotypes are face profile, tail type, and compactness; accounting for 83.48, 17.95, and 2.93 % respectively of the total variability among breeds. The flock structure are affected by the market demand; requirements of breeding females and feed availability. Farmers tend to keep more female sheep for longer (culling age of 5.9?±?0.4 and 1.9?±?0.5 for females and males, respectively) for the reasons of feed shortage and need to maximize number of breeding female. The ratio of male to overall female is large (1:6) and thus a single ram gets maximum contact time with ewes and ewe lambs. The overall average age at puberty for females is 9–14 months. However, the presence of very young lamb rams and uncontrolled mating system lead to early breeding of females which results in low conception rate, low birth weight, poor survival rates, and in extreme cases causing inbreeding. It was also possible to identify the critical control points such as breed, age of animals, nutrition, and feeding systems affecting the provision of live animals for good meat quality.     

Trends in genotype frequency resulting from breeding for resistance to classical scrapie in Belgium (2006~2011)

In sheep, susceptibility to scrapie is mainly determined by codons 136, 154, and 171 of the PRNP gene. Five haplotypes are usually present (ARR, ARQ, ARH, AHQ, and VRQ). The ARR haplotype confers the greatest resistance to classical scrapie while VRQ renders animals most susceptible. In 2004, the European Union implemented a breeding program that promotes selection of the ARR haplotype while reducing the incidence of VRQ. From 2006 to 2011 in Belgium, frequency for the ARR/ARR genotypes increased from 38.3% to 63.8% (n = 6,437), the ARQ haplotype diminished from 21.1% to 12.9%, and the VRQ haplotype decreased from 2.0% to 1.7%. The status of codon 141, a determinant for atypical scrapie, was also evaluated. Out of 27 different breeds (n = 5,163), nine were abundant. The ARR/ARR frequency increased in eight of these nine major breeds. The selection program has had a major impact on the ARR haplotype frequency in Belgium. However, the occurrence of atypical scrapie represents a critical point for this program that warrants the continuous monitoring of scrapie. Additionally, genotype frequencies among the breeds varied greatly. Texel, a breed that is common in Belgium, can still be selected for due to its average ARR frequency.     

PrP genotype progression in flocks participating in the National Scrapie Plan for Great Britain

The National Scrapie Plan (NSP) for Great Britain is a voluntary scheme that, through PrP genotype testing and restricted breeding, aims to reduce the risk of scrapie in the national sheep flock. To gauge the progress in member flocks and within breeds, the genotype profile of successive crops of ram lambs was monitored between 2002 and 2004. In each of the 11 most frequently sampled breeds, the proportion of ram lambs testing in the most resistant genotype category (NSP type 1: ARR/ARR) increased, and there was a reduction in the proportion of genotypes associated with the highest disease risk, that is X/VRQ, where X is an allele other than ARR. Changes in the proportion of ram lambs testing for ARR-heterozygous genotypes (NSP type 2: ARR/X, where X is not VRQ) appeared to be influenced by whether the sheep were hill breeds or non-hill breeds. In each of six frequently sampled hill breeds these genotypes expanded, in relative terms, whereas they declined in four of five prominent lowland/crossing breeds. The proportion of ram lambs that carried neither ARR nor VRQ (NSP type 3) declined consistently in the top 11 breeds, but there was little change in the ARR/VRQ genotype (NSP type 4). Among individual flocks that had ram lambs tested in all three years 2002 to 2004, the majority experienced an increase in the proportion testing ARR/ARR, and of those that had VRQ ram lambs in 2002, most recorded a decrease in their frequency by 2004.