Chronic progressive external ophthalmoplegia (CPEO) plus syndrome due to pathogenic biallelic variants in TOP3A gene has been described in only one single patient.
We report two adult siblings with ...c.614A>G (p.Asp205Gly) homozygous missense variant in the TOP3A gene who had CPEO plus syndrome.
Breeding programs have an essential role in the recovery of threatened populations through optimal genetic management and mating strategies. The dama gazelle (Nanger dama) is a North African ungulate ...listed as critically endangered. The mhorr subspecies is extinct in the wild and currently survives thanks to the creation in 1971 of an ex situ breeding program. The aim of the present study was to assess the evolution of genetic variability in this mhorr gazelle captive population, as well as the mating strategy used in two reference populations studied (Almeria and Europe). The entire pedigree, with 2739 animals, was analyzed to measure demographic characters, pedigree completeness level, probability of gene origin, level of relatedness and genetic structure of the population. The population size has been progressively increasing, with up to 264 individuals alive in Europe at the time of the study. The average number of equivalent complete generations was 5.55. The effective number of founders and ancestors was both 3, and the founder genome equivalent was 1.99. The genetic contributions of the four main ancestors were unbalanced. The average values of inbreeding and average relatedness for the whole pedigree were, respectively, 28.34% and 50.14%. The effective population size was 8.7 by individual increase in inbreeding and 9.8 by individual increase in coancestry. F‐statistics evidenced a very small level of population subdivision (FST = 0.033370). The mating strategy used, based on the minimum coancestry of the individuals, has minimized the losses of genetic variability and helped to balance the genetic contributions between ancestors. The strategy also avoided large subdivisions within the population and the appearance of new bottlenecks. This study shows how pedigree analysis can both be used to determine the genetic variability of the population and to assess the influence of the mating strategy used in the breeding program on such variability.
This paper describes the genetic characterization of the mhorr gazelle population in captivity obtained through pedigree analysis. The genetic variability evolution shows how the mating strategy used has allowed maximizing the genetic potential of the population despite the low number of founders. The study of two living reference populations has made it possible to know the level of current genetic variability.
Solar energy (SE) is essential for the decarbonization of our economy and for energetic transition. Solar energy can be a sustainable economic activity, as long as a balance is struck between the ...benefits it brings to climate change mitigation and the damage it can cause to biodiversity and ecosystems. Here, we study this balance in an area with high biodiversity under pressure for installation of numerous photovoltaic plants (PPs). Our results show that developers give priority to the cheapest land close to connection points, while other values (e.g., environmental, landscape) are secondary. The regulatory process carried out by the Administration does not ensure the preservation of natural values, as several PPs with a high impact on important conservation areas have been approved. Experts’ allegations provide quality information to the Administration to evaluate and demand changes to the projects presented. Such demands show that companies are willing to relocate plants to land occupied by olive groves. In this way, greater efficiency is achieved in land occupation, as well as shorter evacuation lines, water savings and a smaller environmental impact. Prior strategic territorial planning could have avoided the impact of PPs already built, made the deployment of new PPs compatible with biodiversity conservation, and contributed to improving the management of key resources, such as subway aquifers. The proposed regulatory changes to the environmental assessment procedure (exclusion of renewables and public participation from the procedure) are detrimental, as they will make SE unable to meet the requirements of the Taxonomy Regulation.
Animals from zoological institutions may be used for reintroductions. These individuals are considered healthy, but they are not necessarily free of parasites, despite the minimum husbandry standards ...required of zoological institutions as described in the European Association of Zoos and Aquaria guidelines. In this sense, parasitism has been identified as the cause of failure, or has added difficulties, in some reintroduction programmes. Here the authors attempt to summarise the risk of parasitism to animals originating from zoological institutions by analysing a questionnaire about parasite prevalence, sampling methods, treatment and control in three ungulates in European zoos. Completed questionnaires were received from 38 institutions (58.5 per cent response rate). Most of the responding institutions (97 per cent) detected the eggs of endoparasites in faeces, but only one reported ectoparasites. Most institutions followed a similar preventive schedule, with ivermectin as the preferred prophylactic treatment for parasites, commonly administered in food every six months. The frequent use of concentrating flotation techniques as the sole method to evaluate the presence of parasite eggs in faecal samples is not recommended because it fails to detect trematode and lung nematode infections, so it would be better to use flotation techniques together with sedimentation procedures or serological and molecular tests. The results suggest that parasite control in zoological institutions can be complicated, indicating the need to implement a specific management schedule for institutions involved in reintroduction projects.
Captive breeding of endangered species often aims at preserving genetic diversity and to avoid the harmful effects of inbreeding. However, deleterious alleles causing inbreeding depression can be ...purged when inbreeding persists over several generations. Despite its great importance both for evolutionary biology and for captive breeding programmes, few studies have addressed whether and to which extent purging may occur. Here we undertake a longitudinal study with the largest captive population of Cuvier's gazelle managed under a European Endangered Species Programme since 1975. Previous results in this population have shown that highly inbred mothers tend to produce more daughters, and this fact was used in 2006 to reach a more appropriate sex-ratio in this polygynous species by changing the pairing strategy (i.e., pairing some inbred females instead of keeping them as surplus individuals in the population). Here, by using studbook data we explore whether purging has occurred in the population by investigating whether after the change in pairing strategy a) inbreeding and homozygosity increased at the population level, b) fitness (survival) increased, and c) the relationship between inbreeding and juvenile survival, was positive. Consistent with the existence of purging, we found an increase in inbreeding coefficients, homozygosity and juvenile survival. In addition, we showed that in the course of the breeding programme the relationship between inbreeding and juvenile survival was not uniform but rather changed over time: it was negative in the early years, flat in the middle years and positive after the change in pairing strategy. We highlight that by allowing inbred individuals to mate in captive stocks we may favour sex-ratio bias towards females, a desirable managing strategy to reduce the surplus of males that force most zoos to use ethical culling and euthanizing management tools. We discuss these possibilities but also acknowledge that many other effects should be considered before implementing inbreeding and purging as elements in management decisions.
Consanguineous couples have an increased risk of severe diseases in offspring due to autosomal recessive disorders. Exome sequencing (ES) offers the possibility of extensive preconception carrier ...screening (PCS) in consanguineous couples who may be at risk of rare genetic disorders.
We retrospectively analysed ES data from 65 probands affected with rare genetic disorders born from consanguineous couples. We explored diagnostic yield and carrier status for recessive disorders.
The overall diagnostic yield in a singleton approach was 53.8%, mostly recessive variants. In a hypothetical exome-based PCS, only 11.7% of these causative rare variants would have been missed in the filtering process. Carrier screening for recessive conditions allowed the identification of at least one additional pathogenic or likely pathogenic variant in 85.7% of the probands, being the majority with a gene carrier frequency <1 in 200. In addition, considering only clinically actionable conditions, we estimated that 12.3% of our close consanguineous couples may be at risk for an additional recessive disease.
Our results demonstrate that ES outperforms panel-based screening in a PCS context in consanguineous couples and could potentially increase their reproductive autonomy and facilitate informed decision-making.
•TANGO2 deficiency may cause intellectual disability and limb-girdle myopathy.•Phenotypic variability is common amongst patients with TANGO2 deficiency.•The present case extends the clinical spectrum ...of TANGO2-related disease.
TANGO2-related disease is an autosomal recessive multisystem disease associated with developmental delay and infancy-onset recurrent metabolic crises with early mortality. Several studies have reported dysfunction in endoplasmic reticulum-to-Golgi traffic and mitochondrial homoeostasis as the underlying pathophysiology. We report a 40-year-old woman affected by limb-girdle weakness and mild intellectual disability caused by the recurrent deletion of exons 3–9 in homozygosity in the TANGO2 gene. Physical examination revealed hyperlordosis, waddling gait, calf pseudohypertrophy, and Aquilian tendon retractions. Laboratory investigations revealed elevation of serum biomarkers suggestive of mitochondrial dysfunction together with hypothyroidism. At the age of 24, the patient suffered a metabolic crisis with severe rhabdomyolysis and malignant cardiac arrhythmia. After recovery, no metabolic or arrhythmic crisis has recurred. Muscle histology two years later revealed increased endomysial fibrosis and other myopathic changes. Our findings illustrate the mildest end of the phenotypic spectrum of TANGO2-related disease and reveal further aspects related to chronic muscle damage in this disorder.
RRM2B encodes the p53-inducible small subunit (p53R2) of ribonucleotide reductase, a key protein for mitochondrial DNA (mtDNA) synthesis. Pathogenic variants in this gene result in familial ...mitochondrial disease in adults and children, secondary to a maintenance disorder of mtDNA. This study describes two patients, mother and son, with early-onset chronic progressive external ophthalmoplegia (PEO). Skeletal muscle biopsy from the latter was examined: cytochrome c oxidase (COX)-negative fibres were shown, and molecular studies revealed multiple mtDNA deletions. A next-generation sequencing gene panel for nuclear-encoded mitochondrial maintenance genes identified two unreported heterozygous missense variants (c.514 G > A and c.682 G > A) in the clinically affected son. The clinically affected mother harboured the first variant in homozygous state, and the clinically unaffected father harboured the remaining variant in heterozygous state. In silico analyses predicted both variants as deleterious. Cell culture studies revealed that patients' skin fibroblasts, but not fibroblasts from healthy controls, responded to nucleoside supplementation with enhanced mtDNA repopulation, thus suggesting an in vitro functional difference in patients' cells. Our results support the pathogenicity of two novel RRM2B variants found in two patients with autosomal recessive PEO with multiple mtDNA deletions inherited with a pseudodominant pattern.
The use of captive-bred animals as founder stock for reintroduction is sometimes discouraged due to their low genetic diversity and even accumulation of deleterious alleles. In October 2016, 43 ...Cuvier’s gazelles (12 males and 31 females), managed under a European Endangered Species Programme (EEP) and housed in captivity, formed the base of a reintroduction project in Tunisia. The project approach used soft-release techniques. Upon arrival, animals were released in acclimatisation pens, so they could adjust to the new conditions gradually before true release. This study reports on the three-year period gazelles were in the acclimatisation pens before release into the wild. To assess the suitability of captive-bred Cuvier’s gazelles as founder stock for reintroduction, the demographic parameters of the reintroduced population were studied for three reproductive seasons in Tunisia (2017–2019). The demographic parameters of the reintroduced population were also compared to those from the source captive population as a control during the first breeding season. If the animals used as founders were unsuited, a decrease in demographic parameters could be expected over time in the reintroduced population, as well as lower demographic variables compared to the source population. Contrary to expectations, during the three-year study period, all demographic variables increased in the population reintroduced in Tunisia, except juvenile mortality, which decreased. Moreover, none of the demographic values of the gazelles in Tunisia were significantly different from the source population. We hypothesize that in the extremely bottlenecked captive Cuvier’s gazelle population used as founder stock, genetic diversity was still high enough to surmount the presumably deleterious effects of inbreeding. This is probably due to very high heritability (h2), a parameter providing information on the quantitative genetic variation associated with multi-locus quantitative traits previously found in this population. Although reintroduction programs have traditionally been undertaken purely as management exercises, ours was designed to meet a research objective as well. We wanted to find out the adaptive variation in sex ratio in offspring of female Cuvier’s gazelles using the size of the enclosure as a proxy reflecting their body condition. As found in captivity using consanguinity level as a proxy of body condition, in the reintroduced population, mothers in large enclosures produced more daughters while those in the small ones produced more sons, which supports adaptive manipulation of the birth sex ratio favoured by natural selection in reintroduced Cuvier’s gazelles.
•Reintroductions from captive bred animals does not necessarily hinder success.•Demographic metrics of reintroduced population increased almost double.•Heritability (h2) is a suitable predictor of the genetic diversity in this species.•The health protocol performed has done well in establishing a healthy population.•This reintroduction provides the opportunity for testing sex allocation hypothesis.
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