A Comparison of Disease Risk Analysis Tools for Conservation Translocations

Conservation translocations are increasingly used to manage threatened species and restore ecosystems. Translocations increase the risk of disease outbreaks in the translocated and recipient populations. Qualitative disease risk analyses have been used as a means of assessing the magnitude of any effect of disease and the probability of the disease occurring associated with a translocation. Currently multiple alternative qualitative disease risk analysis packages are available to practitioners. Here we compare the ease of use, expertise required, transparency, and results from, three different qualitative disease risk analyses using a translocation of the endangered New Zealand passerine, the hihi (Notiomystis cincta), as a model. We show that the three methods use fundamentally different approaches to define hazards. Different methods are used to produce estimations of the risk from disease, and the estimations are different for the same hazards. Transparency of the process varies between methods from no referencing, or explanations of evidence to justify decisions, through to full documentation of resources, decisions and assumptions made. Evidence to support decisions on estimation of risk from disease is important, to enable knowledge acquired in the future, for example, from translocation outcome, to be used to improve the risk estimation for future translocations. Information documenting each disease risk analysis differs along with variation in emphasis of the questions asked within each package. The expertise required to commence a disease risk analysis varies and an action flow chart tailored for the non-wildlife health specialist are included in one method but completion of the disease risk analysis requires wildlife health specialists with epidemiological and pathological knowledge in all three methods. We show that disease risk analysis package choice may play a greater role in the overall risk estimation of the effect of disease on animal populations involved in a translocation than might previously have been realised.     

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation.

     

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation.     

Streamlining Disease Risk Analysis for Wildlife Using the Shark Bay Bandicoot as a Model

Disease risk analysis (DRA) is a process for identifying significant disease risks and proposing measures to mitigate those risks. Although numerous methodologies for DRA exist, the IUCN Disease Risk Analysis Manual Jakob-Hoff et al. (World Organisation for Animal Health, Paris, pp 160, 2014) remains the gold standard for wild animal translocations. In some cases, however, constraints of time or resources demand compromises on the ideal methodology, and a cost–benefit assessment is required to determine the best approach. We propose a methodology modified from Jakob-Hoff et al. (World Organisation for Animal Health, Paris, pp 160, 2014) and Sainsbury and Vaughan-Higgins (Conserv Biol 26:442–452, 2012), using translocations of the Shark Bay bandicoot (SBB) (Perameles bougainville) as an example. In this study, 44 hazards were identified and described for Peramelidae species. We used hazard prioritization and “scoping” to develop a shortlist of hazards for detailed risk assessment, which excluded 35 of these hazards from further assessment. This approach enabled timely, efficient and cost-effective completion of the DRA while maintaining transparent evaluation of all disease risks. We developed a disease risk management strategy for SBB based on structured, evidence-based analysis of current information and established biosecurity practices and disease screening recommendations for future translocations. Our approach demonstrates a practical process for DRA and risk mitigation, which delivered management outcomes despite limited resources, variable knowledge of disease epidemiology and uncertain translocation pathways for the target species. Limitations are acknowledged, and further research will aim to objectively test this methodology compared to other available methods.

     

Biosecurity for Translocations: Cirl Bunting (Emberiza cirlus), Fisher’s Estuarine Moth (Gortyna borelii lunata), Short-Haired Bumblebee (Bombus subterraneus) and Pool Frog (Pelophylax lessonae) Translocations as Case Studies

Exposure to parasites in conservation translocations increases the risks to recipient and translocated populations from disease, and therefore there has been interest in implementing biosecurity methods. Using four case examples we described how biosecurity was applied in practical translocation scenarios prior to and during a translocation and also post-release. We implemented biosecurity, including quarantine barriers, at specific points in the translocation pathway where hazards, identified by the disease risk analysis, had the potential to induce disease. Evidence that biosecurity protected translocated and recipient populations, included an absence of mortality associated with high-risk non-native parasites, a reduction in mortality associated with endemic parasites, the absence of high-risk pathogenic parasites, or associated diseases, at the destination; and the apparent absence of diseases in closely related species at the destination site. The biosecurity protocols did not alter the level or duration of translocated species confinement and therefore probably did not act as a stressor. There is a monetary cost involved in biosecurity but the epidemiological evidence suggests that conservation translocation managers should carefully consider its use. Breakdowns in quarantine have occurred in human hospitals despite considerable investment and training for health professionals, and we therefore judge that there is a need for training in the objectives and maintenance of quarantine barriers in conservation translocations. Biosecurity protocols for conservation translocations should be continually updated in response to findings from disease risk analysis and post-release disease surveillance and we recommend further studies to evaluate their effectiveness.

     

Segregation of chromosomes in sperm of reciprocal translocation carriers: a review

Reciprocal translocations, the most frequent structural aberration in humans, are mainly transmitted by one of the parents. In order to analyze the chromosomal content of the spermatozoa from carriers of chromosomal reorganizations, two methods have been used, karyotyping of sperm chromosomes by the human-hamster system and fluorescence in situ hybridization (FISH) in decondensed sperm nuclei. In this work, we review 92 sperm chromosome segregation studies from 85 different reciprocal translocation carriers, including a triple translocation carrier. Using the human-hamster method, a total of 5,818 spermatozoa from 44 reciprocal translocation carriers have been analyzed, 43 of them carrying a single reciprocal translocation and one was a carrier of a double reciprocal translocation. A segregation analysis in a carrier of a t(2;22;11) has been also reported. Carrying out FISH in sperm nuclei, a total of 237,042 spermatozoa from 46 reciprocal translocation carriers have been analyzed. Six of these were also analyzed by the human-hamster system. Taking into account both methods, a total of 76 different reciprocal translocations have been studied. In 74 of these 76 translocations, the reorganization occurs between autosomes, and in the other two, the Y chromosome is involved. Although along general lines, there are similarities between the results obtained by the two methods of analysis, variations are observed when the distribution of the different types of segregations that produce imbalances is compared. As a general rule reciprocal translocation carriers produce more unbalanced sperm than normal or balanced sperm. The results reported also corroborate that the proportion of unbalanced forms depends on the characteristics of the reorganization and that it varies widely. Thus the importance of performing a detailed meiotic behavior analysis for each particular translocation in order to obtain enough information to give adequate genetic counseling is stressed. Aspects as to the possible overestimation of 3:1 segregations or the presence of interchromosomal effects still need to be elucidated.     

Response of mouse spermatogonial stem cells to X-ray induction of heritable reciprocal translocations

Although heritable translocations are an important endpoint for the assessment of genetic risk from radiation, there has been a serious information gap with regard to thier induction in spermatogonical stem cells, the most important cell stage in males for risk considerations. This led to uncertainty in estimating the magnitude of risk per unit exposure. Further, the relationship between the frequency of r eciprocal exchanges scored by cytological analysis of the exposed male's meiocytes and the frequency of those transmitted to first-generation offspring needed to be re-examined. In order to fill in these gaps, two radiation studies, i.e., dose response and dose fractionation, were conducted on spermatogonial stem cells in which heritable and cytologically detected translocations were scored.The present data are by far the most extensive, to date, for heritable translocation induction in spermatogonial stem cells. The linearity of the rising portion of the dose-effect curve and the additivity of effects observed in the fractionation study allow a direct estimation of the number of transmissible translocations expected per unit exposure. Thus,t he expected increase in heritable translocations per rad of acute X-rays in 3.89 × 10^?5 per gamete. The data also show a lack of consistensy between cytologically and genetically scored translocations.     

Monitoring for the Management of Disease Risk in Animal Translocation Programmes

Monitoring is best viewed as a component of some larger programme focused on science or conservation. The value of monitoring is determined by the extent to which it informs the parent process. Animal translocation programmes are typically designed to augment or establish viable animal populations without changing the local community in any detrimental way. Such programmes seek to minimize disease risk to local wild animals, to translocated animals, and in some cases to humans. Disease monitoring can inform translocation decisions by (1) providing information for state-dependent decisions, (2) assessing progress towards programme objectives, and (3) permitting learning in order to make better decisions in the future. Here we discuss specific decisions that can be informed by both pre-release and post-release disease monitoring programmes. We specify state variables and vital rates needed to inform these decisions. We then discuss monitoring data and analytic methods that can be used to estimate these state variables and vital rates. Our discussion is necessarily general, but hopefully provides a basis for tailoring disease monitoring approaches to specific translocation programmes.     

Phylogeny reconstruction: increasing the accuracy of pairwise distance estimation using Bayesian inference of evolutionary rates

Distance-based methods for phylogeny reconstruction are the fastest and easiest to use, and their popularity is accordingly high. They are also the only known methods that can cope with huge datasets of thousands of sequences. These methods rely on evolutionary distance estimation and are sensitive to errors in such estimations. In this study, a novel Bayesian method for estimation of evolutionary distances is developed. The proposed method enables the use of a sophisticated evolutionary model that better accounts for among-site rate variation (ASRV), thereby improving the accuracy of distance estimation. Rate variations are estimated within a Bayesian framework by extracting information from the entire dataset of sequences, unlike standard methods that can only use one pair of sequences at a time. We compare the accuracy of a cascade of distance estimation methods, starting from commonly used methods and moving towards the more sophisticated novel method. Simulation studies show significant improvements in the accuracy of distance estimation by the novel method over the commonly used ones. We demonstrate the effect of the improved accuracy on tree reconstruction using both real and simulated protein sequence alignments. An implementation of this method is available as part of the SEMPHY package.     

Causes of oncogenic chromosomal translocation

Non-random chromosomal translocations are frequently associated with a variety of cancers, particularly hematologic malignancies and childhood sarcomas. In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms that cause these translocations remain poorly understood. Illegitimate V(D)J recombination, class switch recombination, homologous recombination, non-homologous end-joining and genome fragile sites all have potential roles in the production of non-random chromosomal translocations. In addition, mutations in DNA-repair pathways have been implicated in the production of chromosomal translocations in humans, mice and yeast. Although initially surprising, the identification of these same oncogenic chromosomal translocations in peripheral blood from healthy individuals strongly suggests that the translocation is not sufficient to induce malignant transformation, and that complementary mutations are required to produce a frank malignancy.     

The use of new technologies in the detection of balanced translocations in hematologic disorders

The cytogenetic evaluation of hematologic disease can confirm a diagnosis, determine treatment options, and provide prognostic information to the patient. Among the potential cytogenetic aberrations that can be identified are certain balanced translocations with recurrent breakpoints that provide disease classification and define the sites of disease-causing or disease-promoting genes. In this review, we discuss the importance of balanced translocation identification, the methods traditionally used to identify balanced translocations in the cytogenetics laboratory, and the application of new methodologies such as next generation (NextGen) sequencing and array-based translocation identification through a linear amplification application. These new technologies have the potential to identify all currently known diagnostically and prognostically important rearrangements as well as novel alterations that may provide new therapeutic targets to enhance treatment of hematologic disease.     

Review and analysis of Australian macropod translocations 1969–2006

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Translocations in stock strains ofAspergillus nidulans

Genetic methods for detection and analysis of translocations are described and illustrated with the case of a translocation involving linkage groups I and VII. Methods are outlined for ascertaining standard chromosome complements in stock strains ofA. nidulans, which show high frequency of translocations, and the general importance of chromosomal rearrangements in micro-organisms is emphasized.     

Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment.     

Le risque chromosomique pour un patient porteur d'une translocation t(X;2) concerne non seulement la translocation mais aussi la ségrégation XY

In men, translocations involving sex chromosomes usually result in azoospermia or sometimes oligospermia. We report the case of a man with oligospermia with a 46,Y,t(X;2)(p21;p25.3) translocation and the specific modalities of management of the couple before ICSI. After genetic counselling, we proposed spermatozoa chromosomal analysis using FISH to evaluate the mode of segregation of the translocation and the risk for the embryo and descendants. This study showed that 34% of spermatozoa were normal or balanced for the chromosomes studied, and 66% of spermatozoa presented a chromosome imbalance related to the translocation and/or involving X and Y chromosome non-disjuction. In view of this result, we decided to perform another FISH analysis to define the increased risk related to the non-disjunction of X and Y chromosomes. Only 60% of 1,000 spermatozoa were normal for X and Y. The chromosome risk for the offspring is not limited to the translocation, as the risk of Klinefelter and Turner syndrome is also increased. In view of these results and the woman's age (42 years old), we advised the couple against ICSI at another genetic counselling session. This case illustrates the value of spermatozoa FISH analysis to evaluate the consequences of a translocation on spermatogenesis. The study should not be limited to the translocation alone, but should also evaluate anomalies of non-disjunction of sex chromosomes that are frequent during normal spermatogenesis, but the risk increases in the case of translocations, especially involving the sex chromosomes.     

Genetic counseling in cases of chromosome insertions]

The principles of the estimation of the risk of repeated birth of malformed child and spontaneous abortion in families of balanced carriers of insertions are presented. A risk for a carrier is formed from two parts: a risk for a carrier of reciprocal translocation and a risk for a carrier of insertion of the came length as inseried segment. The first component of the risk is a constant, the latter one is a variable. It depends on the length of the inserted segment, the type of its inclusion (direct or inverted) and sites of break points. An estimation of the risk in hypothetical insertion 46, XX, inv ins (4; 2) (q24; q22q34) is described as a model. The same method of counselling may be used for the families with triple translocations t(a-, b-, c+) with "insertion" of fragment of chromosome "a" between the parts of "b" and "c" chromosomes. A tentative empirical mean value of repeated birth of malformed child and spontaneous abortion in families with insertions is 29% and 45% for the female carrier, and about 37% and 25% for the male carrier.     

A method for accurate detection of translocation junctions in ewing family of tumors

The Ewing family of tumors (ET) generally contain translocations involving the EWS gene and the FLI or ERG genes. Identification of the translocation confirms the diagnosis of ET. Currently, diagnosis of the translocation is made by several methods. In general, these methods require different primer sets for amplifying different translocations and subsequent efforts to identify the amplified product. The need to employ different sets of primers to amplify different translocation junctions presents some limitations. We have developed a method based on PCR with consensus primers followed by direct automated sequencing of the amplified product. With this method we have correctly determined known as well as unknown ET-associated EWS-FLI and EWS-ERG translocations in appropriate specimens. Use of our consensus primers eliminates the need for separate PCRs to amplify EWS-FLI and EWS-ERG translocation junctions, and because direct sequencing is used for confirming the identity of the amplification product, the accuracy of detection becomes 100%. The method might also accurately diagnose ET-associated translocations other than EWS-FLI and EWS-ERG translocations.     

Evaluating the role of environmental familiarity and behaviour in the success of wildlife translocation: A grizzly bear case study using agent-based modelling

Human-carnivore systems are built on multi-scalar complex processes often resulting in conflicts that force wildlife managers to address what are conceived as problem individuals. In North America, the grizzly bear (Ursus arctos) is often involved in human-bear conflict with management measures such as translocations, in which problem individuals are moved to new areas, being used to reduce conflict risk. While translocations offer a non-lethal alternative to managing conflict animals, they show varying levels of success. Our objective was to perform a novel assessment of grizzly bear translocation success through agent-based simulation by evaluating how familiarity with landscape features coupled with behavioral traits affects the way individuals use resources in a new environment. Our results showed that bears translocated to familiar habitat used high-quality habitat more than bears moved to areas with unfamiliar landscape characteristics. Increased exploration led to greater use of high-quality habitat in the long run but resulted in reduced use of high-quality habitat during the first two years following a translocation. Habitat quality use depended on scale, with bears translocated to less familiar environments accessing higher quality areas at a finer scale than bears translocated to familiar habitats. We emphasize the need to account for wildlife behavioral traits and habitat characteristics at multiple scales when selecting suitable translocation locations. Understanding the role of factors such as these on translocation outcome will help ensure the success of translocations not only as a method for managing problem wildlife, but also for population restoration, species reestablishment, and conservation translocations across the globe.     

Cause‐Specific Cumulative Incidence Estimation and the Fine and Gray Model Under Both Left Truncation and Right Censoring

Summary The standard estimator for the cause‐specific cumulative incidence function in a competing risks setting with left truncated and/or right censored data can be written in two alternative forms. One is a weighted empirical cumulative distribution function and the other a product‐limit estimator. This equivalence suggests an alternative view of the analysis of time‐to‐event data with left truncation and right censoring: individuals who are still at risk or experienced an earlier competing event receive weights from the censoring and truncation mechanisms. As a consequence, inference on the cumulative scale can be performed using weighted versions of standard procedures. This holds for estimation of the cause‐specific cumulative incidence function as well as for estimation of the regression parameters in the Fine and Gray proportional subdistribution hazards model. We show that, with the appropriate filtration, a martingale property holds that allows deriving asymptotic results for the proportional subdistribution hazards model in the same way as for the standard Cox proportional hazards model. Estimation of the cause‐specific cumulative incidence function and regression on the subdistribution hazard can be performed using standard software for survival analysis if the software allows for inclusion of time‐dependent weights. We show the implementation in the R statistical package. The proportional subdistribution hazards model is used to investigate the effect of calendar period as a deterministic external time varying covariate, which can be seen as a special case of left truncation, on AIDS related and non‐AIDS related cumulative mortality.     

Construction and uses of new compound B-A-A maize chromosome translocations

Maize B-A translocations result from reciprocal interchanges between a supernumerary B chromosome and an arm of an essential A chromosome. Because of the frequent nondisjunction of the B centromere at the second pollen mitosis, B-A translocations have been used to locate genes to chromosome arms and to study the dosage effects of specific A segments. Compound B-A translocations (B-A-A translocations) are created by bringing together a simple B-A translocation with an A-A translocation in which breakpoints in the A-A and B-A translocations are in the same arm. Recombination in the region of shared homology of these A chromosome segments creates a B-A-A translocation. Success in creating and testing for a new B-A-A translocation requires that the B-A translocation be proximal to the A-A translocation and that the A-A translocation be proximal to the tester locus. The breakpoints of most of the A-A translocations have been cytologically defined by earlier investigators. Previous investigators have produced 16 B-A-A translocations and one B-A-A-A translocation, which collectively define 35 A chromosome breakpoints. We have enlarged this group by creating 64 new B-A-A translocations. We present a summary of the total of 81 B-A-A translocations showing their distribution among the chromosome arms and the 163 cytologically defined chromosome segments delimited by them. We also illustrate the method of construction of these B-A-A stocks and their uses.