The impact of incorrectly recorded parentage on inferred genotypes over multiple generations.

The absence of selective pressure against recessive deleterious mutations in the heterozygous state means that virtually every individual will carry several such mutations which have arisen over time. The inflation in frequency of a few of these mutations due to selective processes during domestication and breed formation have left modern domestic dog breeds with a high burden of genetic disease due to mutations at single genes. This has stimulated research into the causal mutations, and a consequential market in DNA tests, which enable breeders to distinguish heterozygotes from wild type homozygotes and determine pairings that will avoid producing diseased progeny. The genotypes of progeny of parents with known genotypes themselves may in some cases be definitively inferred. Importantly, two parents homozygous for non-disease causing alleles, will produce progeny with the same genotype, which may be assigned to the offspring (e.g. as 'hereditary clear') without the need for further testing. However, the veracity of assigned genotypes is dependent on the parentage being recorded without error, which is not the case in most species. Simulations presented here demonstrate that a modest rate of false paternity can result in a notable proportion of 'hereditary clear' assignments being false when 'hereditary clear' status is assigned across a number of generations (error rates exceeding 5% after 6 generations with a disease causing mutation frequency of 0.2). Erroneous assignment of 'hereditary clear' genotypes risks the production of puppies with the very disease for which a DNA test is available allowing avoidance. In light of these findings and to reduce the risks of producing puppies destined to be affected by such diseases, the Kennel Club has determined to limit the assignment of 'hereditary clear' status of registered dogs to 2 generations, with effect from January 2022.

Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test.

INTRODUCTION: DNA testing for autosomal recessive disease mutations in many dog breeds is now relatively commonplace. There have, however, been few efforts made to determine changes in the frequency of disease causing mutations as a result of probable selection based on the results of DNA testing. This study makes use of genotype data from both DNA test results reported to the UK Kennel Club and where known from a 'hereditary status' (where a definitive genotype may be inferred and ascribed based on known parental genotypes) to do so. RESULTS: The results, using all known genotype data, show a general and sizeable decline in disease causing mutation frequency across eight diseases in eight breeds (by between 12-86% in dogs born 2-4 years after publication of the mutation, and by nearly 90% or more in those born 8-10 years after). In contrast, data from test results only, while revealing an almost complete and immediate end to the production of affected individuals, show little general decline in either the derived mutation frequency or the proportion of heterozygote carriers. It appears that the numerical size of the breed is an important determinant on the rate of uptake of a DNA test (as judged by the proportion of a breed born four years after publication of the disease-causing mutation with a known genotype). CONCLUSION: These results show that dog breeders appear to be incorporating the results of DNA testing into their selection strategies to successfully decrease the frequency of the mutation. It is shown that use of DNA test result data alone does not reveal such trends, possibly as some breeders undertake testing to determine clear stock which can then be used to produce future disease-free generations in the knowledge they are not carrying the disease causing mutation.

Longevity and mortality in Kennel Club registered dog breeds in the UK in 2014.

BACKGROUND: The domestic dog is one of the most diverse mammalian species, exhibiting wide variations in morphology, behaviour and morbidity across breeds. Therefore, it is not unexpected that breeds should also exhibit variation in mortality and longevity. While shorter longevity per se may not necessarily be a welfare issue, a generally foreshortened lifespan in a breed that is accompanied by a high prevalence of a particular cause of death may reveal potentially serious welfare concerns and highlight scope to improve breed welfare. Survey data gathered directly from owners offer useful insights into canine longevity and mortality that can support the overall evidence base for welfare reforms within breeds. RESULTS: Mortality data on 5663 deceased dogs registered with the UK Kennel Club were collected from an owner-based survey. The most commonly reported causes of death were old age (13.8%), unspecified cancer (8.7%) and heart failure (4.9%); with 5.1% of deaths reported as unknown cause. Overall median age at death was 10.33 years (interquartile range: 7.17-12.83 years). Breeds varied widely in median longevity overall from the West Highland Terrier (12.71 years) to the Dobermann Pinscher (7.67 years). There was also wide variation in the prevalence of some common causes of death among breeds, and in median longevity across the causes of death. CONCLUSION: Substantial variation in the median lifespan and the prominent causes of death exists across breeds. This study has identified some breeds with both a low median lifespan and also a high proportional mortality for one or more specific causes of death that should be considered as both potential welfare concerns as well as opportunities for improvement.

Preventing skeletal and neurological problems in guide dogs for the blind and other working dogs.

Skeletal and neurological problems consistently rank among the top health conditions necessitating the withdrawal or retirement of guide dogs and other working dogs from their service roles. Management practices such as weight management and physical conditioning may help to reduce the incidence of such conditions. However, where there is at least partial genetic aetiology, selective breeding strategies are the only way to produce a lasting reduction in their incidence in future generations. The management of single gene disorders is relatively simple through the judicious use of DNA test results. Breeding strategies to tackle complex diseases, into which category many skeletal and neurological diseases fall, are more challenging but can be successful through the use of data collected through screening schemes and, most efficiently, through the use of estimated breeding values.

Les troubles squelettiques et neurologiques comptent parmi les principaux problèmes de santé imposant la réforme ou la mise à la retraite des chiens guide d'aveugles et autres chiens de travail. Certaines pratiques de bonne gestion veillant notamment à contrôler le poids et la condition physique des chiens peuvent contribuer à réduire l'incidence de ce type de problèmes. Toutefois, lorsque l'étiologie des problèmes de santé est totalement ou partiellement déterminée par la génétique, les stratégies de sélection constituent le seul moyen de réduire durablement cette incidence pour les générations futures. La gestion de certains troubles dus à un gène unique est relativement aisée, grâce à un emploi judicieux des résultats de tests ADN. Lorsqu'il s'agit de maladies plus complexes, catégorie recouvrant nombre d'infections squelettiques et neurologiques, les stratégies de sélection sont plus difficiles à mettre en oeuvre mais elles peuvent réussir si l'on procède à une collecte de données via des dispositifs de dépistage, ou en recourant aux valeurs d'élevage estimées, qui déterminent encore plus efficacement le potentiel génétique d'un chien.

Los problemas esqueléticos y neurológicos se sitúan sistemáticamente entre las principales dolencias que hacen necesario retirar o jubilar a los perros lazarillos y otros perros de trabajo de las tareas que cumplen al servicio del ser humano. Hay procedimientos de gestión, como la regulación del peso o el condicionamiento físico, que pueden ayudar a reducir la incidencia de este tipo de trastornos. Sin embargo, en los casos en que hay, cuando menos parcialmente, una etiología genética, las estrategias de cría selectiva son el único modo de conseguir una reducción duradera de su incidencia en las generaciones futuras. La gestión de trastornos ligados a un solo gen es relativamente sencilla, pues pasa por un uso juicioso de los resultados de las pruebas de ADN. Las estrategias de cría selectiva para combatir enfermedades complejas, categoría en la que entran muchas enfermedades esqueléticas y neurológicas, plantean mayor dificultad, pero pueden deparar buenos resultados cuando se utilizan datos obtenidos con programas de cribado sistemático y ser de lo más eficaces cuando se aplican empleando valores estimados de cría.

A molecular beam apparatus for performing single photon initiated dissociative rearrangement reactions (SPIDRR) with transition metal cation bound organic clusters.

The study of gas-phase ion-molecule reactions has been influential in the investigation of transition metal mediated bond activation and catalysis. We have furthered this field by developing a new technique capable of measuring the microcanonical kinetics for reactions between transition metal cations and neutral organic molecules. This novel method has been designated as single photon initiated dissociative rearrangement reaction (SPIDRR) technique and provides a nearly direct measurement of microcanonical reaction rate constants. For this reason, SPIDRR offers unique insight into reaction mechanisms and dynamics by assessing the energy dependence of the microcanonical rate constant, as well as measuring product branching fractions and kinetic isotope effects. The following paper provides a detailed overview of SPIDRR and its advantages in the field of gas-phase catalysis research.

Large-scale survey to estimate the prevalence of disorders for 192 Kennel Club registered breeds.

BACKGROUND: Pedigree or purebred dogs are often stated to have high prevalence of disorders which are commonly assumed to be a consequence of inbreeding and selection for exaggerated features. However, few studies empirically report and rank the prevalence of disorders across breeds although such data are of critical importance in the prioritisation of multiple health concerns, and to provide a baseline against which to explore changes over time. This paper reports an owner survey that gathered disorder information on Kennel Club registered pedigree dogs, regardless of whether these disorders received veterinary care. This study aimed to determine the prevalence of disorders among pedigree dogs overall and, where possible, determine any variation among breeds. RESULTS: This study included morbidity data on 43,005 live dogs registered with the Kennel Club. Just under two thirds of live dogs had no reported diseases/conditions. The most prevalent diseases/conditions overall were lipoma (4.3%; 95% confidence interval 4.13-4.52%), skin (cutaneous) cyst (3.1%; 2.94-3.27%) and hypersensitivity (allergic) skin disorder (2.7%; 2.52-2.82%). For the most common disorders in the most represented breeds, 90 significant differences between the within breed prevalence and the overall prevalence are reported. CONCLUSION: The results from this study have added vital epidemiological data on disorders in UK dogs. It is anticipated that these results will contribute to the forthcoming Breed Health & Conservation Plans, a Kennel Club initiative aiming to assist in the identification and prioritisation of breeding selection objectives for health and provide advice to breeders/owners regarding steps that may be taken to minimise the risk of the disease/disorders. Future breed-specific studies are recommended to report more precise prevalence estimates within more breeds.

Automatic determination of EMG-contaminated components and validation of independent component analysis using EEG during pharmacologic paralysis.

OBJECTIVE: Validate independent component analysis (ICA) for removal of EMG contamination from EEG, and demonstrate a heuristic, based on the gradient of EEG spectra (slope of graph of log EEG power vs log frequency, 7-70 Hz) from paralysed awake humans, to automatically identify and remove components that are predominantly EMG. METHODS: We studied the gradient of EMG-free EEG spectra to quantitatively inform the choice of threshold. Then, pre-existing EEG from 3 disparate experimental groups was examined before and after applying the heuristic to validate that the heuristic preserved neurogenic activity (Berger effect, auditory odd ball, visual and auditory steady state responses). RESULTS: (1) ICA-based EMG removal diminished EMG contamination up to approximately 50 Hz, (2) residual EMG contamination using automatic selection was similar to manual selection, and (3) task-induced cortical activity remained, was enhanced, or was revealed using the ICA-based methodology. CONCLUSION: This study further validates ICA as a powerful technique for separating and removing myogenic signals from EEG. Automatic processing based on spectral gradients to exclude EMG-containing components is a conceptually simple and valid technique. SIGNIFICANCE: This study strengthens ICA as a technique to remove EMG contamination from EEG whilst preserving neurogenic activity to 50 Hz.

Trends in genetic diversity for all Kennel Club registered pedigree dog breeds.

BACKGROUND: Inbreeding is inevitable in closed populations with a finite number of ancestors and where there is selection. Therefore, management of the rate of inbreeding at sustainable levels is required to avoid the associated detrimental effects of inbreeding. Studies have shown some pedigree dog breeds to have high levels of inbreeding and a high burden of inherited disease unrelated to selection objectives, implying loss of genetic diversity may be a particular problem for pedigree dogs. Pedigree analysis of all 215 breeds currently recognised by the UK Kennel Club over the period 1980-2014 was undertaken to ascertain parameters describing the rate of loss of genetic diversity due to inbreeding, and the presence of any general trend across all breeds. RESULTS: The trend over all breeds was for the rate of inbreeding to be highest in the 1980s and 1990s, tending to decline after 2000. The trend was comparable in very common and rarer breeds, although was more pronounced in rarer breeds. Rates of inbreeding over the entire period 1980-2014 were not correlated with census population size. The existence of popular sires was apparent in all breeds. CONCLUSION: The trends detected over 1980-2014 imply an initial excessive loss of genetic diversity which has latterly fallen to sustainable levels, even with modest restoration in some cases. The theory of genetic contributions, which demonstrates the fundamental relationship of inbreeding and selection, implies that popular sires are the major contributor to high rate of inbreeding.

Measurement of neural signals from inexpensive, wireless and dry EEG systems.

Electroencephalography (EEG) is challenged by high cost, immobility of equipment and the use of inconvenient conductive gels. We compared EEG recordings obtained from three systems that are inexpensive, wireless, and/or dry (no gel), against recordings made with a traditional, research-grade EEG system, in order to investigate the ability of these 'non-traditional' systems to produce recordings of comparable quality to a research-grade system. The systems compared were: Emotiv EPOC (inexpensive and wireless), B-Alert (wireless), g.Sahara (dry) and g.HIamp (research-grade). We compared the ability of the systems to demonstrate five well-studied neural phenomena: (1) enhanced alpha activity with eyes closed versus open; (2) visual steady-state response (VSSR); (3) mismatch negativity; (4) P300; and (5) event-related desynchronization/synchronization. All systems measured significant alpha augmentation with eye closure, and were able to measure VSSRs (although these were smaller with g.Sahara). The B-Alert and g.Sahara were able to measure the three time-locked phenomena equivalently to the g.HIamp. The Emotiv EPOC did not have suitably located electrodes for two of the tasks and synchronization considerations meant that data from the time-locked tasks were not assessed. The results show that inexpensive, wireless, or dry systems may be suitable for experimental studies using EEG, depending on the research paradigm, and within the constraints imposed by their limited electrode placement and number.

Surface Laplacian of scalp electrical signals and independent component analysis resolve EMG contamination of electroencephalogram.

The serious impact of electromyogram (EMG) contamination of electroencephalogram (EEG) is well recognised. The objective of this research is to demonstrate that combining independent component analysis with the surface Laplacian can eliminate EMG contamination of the EEG, and to validate that this processing does not degrade expected neurogenic signals. The method involves sequential application of ICA, using a manual procedure to identify and discard EMG components, followed by the surface Laplacian. The extent of decontamination is quantified by comparing processed EEG with EMG-free data that was recorded during pharmacologically induced neuromuscular paralysis. The combination of the ICA procedure and the surface Laplacian, with a flexible spherical spline, results in a strong suppression of EMG contamination at all scalp sites and frequencies. Furthermore, the ICA and surface Laplacian procedure does not impair the detection of well-known, cerebral responses; alpha activity with eyes-closed; ERP components (N1, P2) in response to an auditory oddball task; and steady state responses to photic and auditory stimulation. Finally, more flexible spherical splines increase the suppression of EMG by the surface Laplacian. We postulate this is due to ICA enabling the removal of local muscle sources of EMG contamination and the Laplacian transform being insensitive to distant (postural) muscle EMG contamination.

Opportunities for international collaboration in dog breeding from the sharing of pedigree and health data.

Pooling of pedigree and phenotype data from different countries may improve the accuracy of derived indicators of both genetic diversity and genetic merit of traits of interest. This study demonstrates significant migration of individuals of four pedigree dog breeds between Sweden and the United Kingdom. Correlations of estimates of genetic merit (estimated breeding values, EBVs) for the Fédération Cynologique Internationale and the British Veterinary Association and Kennel Club evaluations of hip dysplasia (HD) were strong and favourable, indicating that both scoring schemes capture substantially the same genetic trait. Therefore pooled use of phenotypic data on hip dysplasia would be expected to improve the accuracy of EBV for HD in both countries due to increased sample data.

Canine hip and elbow dysplasia in UK Labrador retrievers.

This paper examines the outcomes from recent genetic analyses of hip and elbow scores from British Veterinary Association (BVA)/UK Kennel Club (KC) screening programmes targeted at reducing the prevalence of hip dysplasia (HD) and elbow dysplasia in UK Labrador retrievers. The analyses made use of 25,243 hip scores and 3613 elbow scores. Heritabilities (± standard error) for hip score, analysed on a log scale, and for elbow score were 0.35±0.02 and 0.19±0.04, respectively, with a genetic correlation of 0.41±0.09. For both hip and elbow scores, there was a near perfect genetic correlation between the left and right joint; analysis of hip score showed a predictive benefit of using the total of left and right scores rather than worst score and the benefit of using all component scores rather than their aggregate score. Downward genetic trends were observed in both hip and elbow scores, although the latter was consistent with it being correlated to response to genetic change in hip score. Estimated breeding values (EBVs) offered substantial benefits in accuracy and hence genetic progress when compared to the use of phenotypes for both hip and elbow scores. There are major opportunities for improving selection against elbow dysplasia through the use of bivariate evaluations, although progress against dysplasia would be improved by more widespread elbow scoring. The studies highlighted a number of ways in which data recording for addressing complex traits may be improved in the future. Ongoing advances in genomic technology may be utilised for increasing the rate of genetic progress in selection against HD and for complex diseases in general, through the use of genomic evaluations.

Genetic evaluation of elbow scores and the relationship with hip scores in UK Labrador retrievers.

A linear mixed model analysis of elbow and hip score data from UK Labrador retrievers was used to estimate the heritability of elbow score (0.16-0.19) and to determine a moderate and beneficial genetic correlation with hip score (0.40). A small improvement in the genetic trend of elbow score was observed during the years 2000-2008, equivalent to avoiding only the worst 3-4% of scored dogs for breeding, but close to what may have been anticipated if the current British Veterinary Association-approved guidelines were followed. Calculations suggested that a correlated response to indirect selection on hip score may elicit a greater response than direct selection on elbow score and that the genetic trend in elbow score may be explained as a consequence of the stronger selection pressure that has been placed on hip score. Increases in the accuracy of estimated breeding values for elbow score of 4-7% for dogs with elbow data only and 7-11% for dogs with both hip and elbow score were observed from bivariate analysis of elbow and hip data. A selection index confirmed the benefits of bivariate analysis of elbow and hip score data by identifying increases in accuracy (directly related to the response to selection) of 14% from the use of optimum coefficients compared to use of hip data only. The quantified genetic correlation means that hip score effectively acts as a 'secondary indicator' of elbow score in this breed and the preponderance of hip data means that it acts as a major source of information that may be used to improve the accuracy of estimates of genetic risk for elbow dysplasia.

Copper/metal ratios in the gills of rainbow trout (Oncorhynchus mykiss) provide evidence of copper exposure under conditions of mixed-metal exposure.

Previous work has suggested that the ratio of copper residues to zinc in the gills of rainbow trout may indicate short-term exposure to increased levels of waterborne copper. However, the effect of exposure to a combination of increased copper and zinc concentrates in the water column was unknown. We exposed rainbow trout to 8 +/- 2 microg L(-1), 40 +/- 2 microg L(-1) and 90 +/- 9 microg L(-1) of waterborne copper and 21 +/- 3 microg L(-1), 129 +/- 40 microg L(-1), and 202 +/- 40 microg L(-1) of waterborne zinc in a 2-factor experiments and gill copper and zinc residues were examined. Other gill parameters analyzed included the concentrations of calcium, magnesium, sodium, and potassium, liver copper and zinc concentrations and plasma copper, calcium, sodium, and potassium are also reported here. Copper residues in the gill filaments were significantly higher in the highest level of copper exposure (high Cu, 4.06 microg g(-1); low Cu 2.41 microg g(-1); 0 Cu 2.01 microg g(-1); P = 0.001), whereas no differences were seen in zinc concentrations at any treatment level. Gill sodium and plasma calcium concentrations were also decreased at the highest waterborne copper concentrations. Although copper-zinc ratios in the gills were significantly different between the highest and lowest copper treatments (P = 0.002, F = 6.59), copper-sodium and copper-magnesium ratios were more sensitive to waterborne copper exposure (P = 0.001, F = 17.91 and P = 0.002, F = 15.45, respectively). These copper-metal ratios may be better indicators of copper loading in the water column.

A novel interactive electronic protocol review system.

This report describes a new protocol review system which was designed as a Lotus Notes database. This system encompasses all elements of investigator protocol generation, review and approval by the laboratory animal veterinarian and institutional animal care and use committee (IACUC), and notification of approval to personnel responsible for animal ordering. Unique features of the system are interactive dialog between IACUC members and the investigator and confidential protocol discussion among IACUC members. The advantages of the system are multiple: 1. it allows for interactive protocol discussion online; 2. it is an essentially paperless process; 3. inclusion of the outside IACUC member is easily accomplished by using an offsite personal computer and secure remote local-area network access; 4. the time required for protocol generation, review, and approval is streamlined due to the automatic features of the database and the speed of e-mail; and 5. all documentation relating to the protocol and the approval process is archived online.

A comparison of peripheral nerve repair using an absorbable tubulization device and conventional suture in primates.

Median nerve regeneration was studied in 30 adult primates after repair by microsurgical suture or tubulization with a nonwoven, bioabsorbable, polyglycolic acid device. The two methods were compared electrophysiologically and histologically 6 and 12 months after repair. The electrophysiology included recording of electrically evoked compound action potentials and subsequent determination of threshold, conduction velocity, amplitude, and area above the baseline for each component. Measurements were obtained before nerve transection and at the time of biopsy by stimulating both proximal and distal to the transection site. Analysis of all electrophysiological parameters revealed no statistically significant differences (p less than 0.05) between the two repair techniques. Histopathology included examination of cross sections proximal and distal to the repair sites and longitudinal sections through the coaptation site. End organs (Meissner's and Pacinian corpuscles and muscle) were sectioned to determine the degree of reinnervation. No significant differences between the repair techniques were observed by histological analysis of these sections. These evaluations indicated that the tubulization repair technique produced results comparable to that of the suture technique.

Evaluation of the Unilink microvascular anastomotic device in the dog.

This experimental study reports the evaluation of a mechanical, non-suture technique for the repair of small blood vessels under the operating microscope. The method uses the Unilink implantable pinned rings on which the vessel ends are everted 90 degrees and impaled on small pins. An instrument approximates the rings and completes the anastomosis. The device was used for the end-to-end anastomosis of 80 vessels in ten beagle dogs. Both arteries (ulnar and saphenous) and veins (cephalic and saphenous) were included in the study. Vessels were assessed for patency and harvested for histologic examination and scanning electron microscopy at 4-, 16-, and 32-week implantation times. Both longitudinal and cross sections were stained using hematoxylin and eosin, Verhoeff-Van Gieson techniques for elastin, and a modified Masson's trichrome for muscle and collagen, and examined under light microscopy. Scanning electron microscopy (SEM) was completed on longitudinally bisected anastomoses. Patency rates, histology, and SEM at all implantation times of the mechanical anastomoses compared favorably with experimental investigations of suturing techniques that have appeared in the literature. This microvascular anastomotic technique provided a rapid, safe, and efficacious method for the end-to-end repair of severed peripheral arteries and veins in the dog model.