Protective effect of the AT137RQ and ARQK176 PrP alleles against classical scrapie in Sarda breed sheep

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.     

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.     

A Necropsy Survey of Neurologic Diseases in 4,319 Horses Examined in Normandy (France) from 1986 to 2006

The frequencies of neurologic diseases and various corresponding causes were analyzed in 4,319 Norman horses examined by autopsy between 1986 and 2006. Five hundred forty-three cases of nervous system disorders were detected, or a total prevalence of 12.6%. One hundred eighty-seven of the 543 horses (34.4%) exhibited lesions of a traumatic origin affecting the skull or the vertebral column at different levels. Their frequency was less in foals younger than 1 month of age and higher in horses aged 6 months to 2 years. Eighty-three cases of cervical vertebral compressive myelopathy (CVCM) (15.3%) were identified. Males and geldings were more often affected than females. CVCM was diagnosed mostly in animals aged 6 months to 2 years. Horses affected with lesions in the mid-cervical region (region C3–C5) were significantly younger than those exhibiting more caudal lesions (region C5–C7). Neonatal maladjustment syndrome was diagnosed in 62 foals younger than 3.5 days (4.8% of the causes of death between birth and 1 month) by using clinical or lesional criteria. The prevalence was higher in Thoroughbreds as well as in the miscellaneous breed category and less in French Standardbreds. Bacterial meningoencephalomyelitis and meningitis represented 9.6% of nervous system disorders (52 cases) and most often affected foals aged 1 to 6 months. The main bacteria identified were beta-hemolytic Streptococci , Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Actinobacillus sp. The other causes diagnosed were, in decreasing order of frequency: grass sickness or equine dysautonomia (6.3% of neurologic diseases), hepatic encephalopathy syndrome (5.2%), septic vertebral arthritis or osteitis mainly caused by Rhodococcus equi (2.6%), congenital defects of the nervous system (2.4%), equine herpesvirus 1 myeloencephalopathy (2.2%), botulism (2.2%), malformations of the vertebral column other than CVCM (2%), and neighboring polyneuritis associated with guttural pouch mycosis (1.5%).