Association of a Bovine Prion Gene Haplotype with Atypical BSE

Background: Atypical bovine spongiform encephalopathies (BSEs) are recently recognized prion diseases of cattle. Atypical BSEs are rare; approximately 30 cases have been identified worldwide. We tested prion gene (PRNP) haplotypes for an association with atypical BSE. Methodology/Principle Findings: Haplotype tagging polymorphisms that characterize PRNP haplotypes from the promoter region through the three prime untranslated region of exon 3 (25.2 kb) were used to determine PRNP haplotypes of six available atypical BSE cases from Canada, France and the United States. One or two copies of a distinct PRNP haplotype were identified in five of the six cases (p = 1.36×10-4, two-tailed Fisher’s exact test; CI95% 0.263–0.901, difference between proportions). The haplotype spans a portion of PRNP that includes part of intron 2, the entire coding region of exon 3 and part of the three prime untranslated region of exon 3 (13 kb). Conclusions/Significance: This result suggests that a genetic determinant in or near PRNP may influence susceptibility of cattle to atypical BSE

Dynamics of localization in a waveguide

This is a review of the dynamics of wave propagation through a disordered N-mode waveguide in the localized regime. The basic quantities considered are the Wigner-Smith and single-mode delay times, plus the time-dependent power spectrum of a reflected pulse. The long-time dynamics is dominated by resonant transmission over length scales much larger than the localization length. The corresponding distribution of the Wigner-Smith delay times is the Laguerre ensemble of random-matrix theory. In the power spectrum the resonances show up as a 1/t^2 tail after N^2 scattering times. In the distribution of single-mode delay times the resonances introduce a dynamic coherent backscattering effect, that provides a way to distinguish localization from absorption.Comment: 18 pages including 8 figures; minor correction

BSE Case Associated with Prion Protein Gene Mutation

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD) in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp). Sequence analysis revealed that the animal with H-type BSE was heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic mutation at the homologous codon position (E200K) in the human Prnp has been described as the most common cause of genetic CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. A recent epidemiological study revealed that the K211 allele was not detected in 6062 cattle from commercial beef processing plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K variant (less than 1 in 2000) in cattle

Tracing Cattle Breeds with Principal Components Analysis Ancestry Informative SNPs

The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs) for 19 breeds (13 taurine, three zebu, and three hybrid breeds), seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products

Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

P300 amplitude is insensitive to working memory load in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects.</p> <p>Methods</p> <p>We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory.</p> <p>Results</p> <p>In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs.</p> <p>Conclusions</p> <p>SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients.</p

PRNP Haplotype Associated with Classical BSE Incidence in European Holstein Cattle

Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE. Methodology/Principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPs) within PRNP were used to test for association between PRNP haplotypes and BSE disease. A combination of Illumina goldengate assay, sequencing and PCR amplification was used to genotype 18 htSNPs and 2 indels in 95 BSE case and 134 control animals. A haplotype within the region of high LD was found to be associated with BSE unaffected animals (p-value = 0.000114). Conclusion/Significance: A PRNP haplotype association with classical BSE incidence has been identified. This result suggests that a genetic determinant in or near PRNP may influence classical BSE incidence in cattle

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

<p>Abstract</p> <p>Background</p> <p>Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP) markers would offer considerable advantages over current short tandem repeat (STR) based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM) algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland.</p> <p>Results</p> <p>6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from each of the breeds were obtained and were observed to be superior to those conferred by the industry standard STR assay.</p> <p>Conclusions</p> <p>The 43 SNPs characterised herein may constitute a starting point for the development of a SNP based DNA identification test for European cattle.</p

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems