July 31, 2024

Fruitful innovation

Fruitful innovation: Transforming watermelon genetics with advanced base editors



The development of new adenine base editors (ABE) and adenine-to-thymine/guanine base editors (AKBE) is transforming watermelon genetic engineering. These innovative tools enable precise A:T-to-G and A:T-to-T base substitutions, allowing for targeted genetic modifications.

The research highlights the efficiency of these editors in generating specific mutations, such as a flowerless phenotype in ClFT (Y84H) mutant plants. This advancement not only enhances the understanding of gene function but also significantly improves molecular breeding, paving the way for more efficient watermelon crop improvement.

Traditional breeding methods for watermelon often face challenges in achieving desired genetic traits efficiently and accurately. While CRISPR/Cas9 has provided a powerful tool for genome editing, its precision and scope are sometimes limited. These limitations highlight the need for more advanced gene-editing technologies.

The development of new base editors, which can introduce specific base changes, represents a significant step forward. Due to these challenges, there is a growing necessity to develop precise and efficient gene-editing techniques to enhance watermelon breeding and achieve more reliable crop improvements.

Researchers from Northwest A&F University and Northeast Agricultural University have published a study in Horticulture Research, on April 23, 2024, detailing the development of adenine base editors (ABE) and adenine-to-thymine/guanine base editors (AKBE) base editors for watermelon. These editors allow precise genetic modifications, potentially improving crop traits and breeding efficiency.

The study introduces three types of adenine base editors (U-ABE, S-ABE, and R-ABE) and evaluates their efficiency in inducing A:T-to-G substitutions in watermelon genes. Among them, R-ABE demonstrated the highest efficiency, particularly at the A5 position of the target gene.

Additionally, the researchers developed S-AKBE and R-AKBE to achieve A:T-to-T mutations, with S-AKBE showing greater efficiency. The successful editing of the ClFT gene to produce the Y84H mutation resulted in a flowerless phenotype, underscoring the potential of these tools in manipulating flowering time and other traits in watermelon.

The findings reveal that the Rps5A promoter used in R-ABE and R-AKBE significantly enhances editing efficiency. Overall, this study highlights the effectiveness of these base editors in achieving precise genetic modifications, paving the way for improved breeding strategies and trait enhancements in watermelon.

Dr. Xian Zhang from Northwest A&F University commented, "The development of these base editors represents a significant breakthrough in plant genetic engineering. These tools not only enhance our ability to study gene function but also pave the way for more precise and efficient crop improvement strategies."

The implementation of ABE and AKBE base editors opens new avenues for watermelon breeding, allowing for the precise introduction of beneficial traits. Future research will focus on optimizing these tools and exploring additional target genes to further enhance the genetic improvement of watermelon and potentially other crops.



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July 30, 2024

Genetic factors with clinical trial stoppage

Genetic factors associated with reasons for clinical trial stoppage


Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to evaluate targets for drug discovery programs.

Main

The drug discovery endeavor is dominated by high attrition rates, and failure remains the most likely outcome throughout the pipeline. A diverse set of factors can lead to failure, with lack of efficacy or unforeseen safety issues reportedly explaining 79% of setbacks in the clinic. New approaches adopted across the industry have aimed to improve success rates by systematically assessing the available evidence throughout the research and clinical pipelines. Support from human genetic evidence has been repeatedly associated with successful clinical trial progression ultimately supporting two-thirds of the drugs approved by the US Food and Drug Administration (FDA) in 2021 (ref. 9). Further understanding of the reasons for success or failure in clinical trials could assist in reducing future attrition.

Systematically assessing the reasons for success or failure in clinical trials can be hampered by many factors. Several surveys have demonstrated a bias towards reporting positive results, with 78.3% of trials in the literature reporting successful outcomes. Successful clinical trials are published significantly faster than trials reporting negative results. However, access to negative results is crucial, not only for revealing efficacy tendencies and safety liabilities but also for retrospective review and benchmarking of predictive methods, including machine learning.

Since 2007, the FDA has required the submission of clinical trial results to ClinicalTrials.gov, a free-to-access global databank aimed at registering clinical research studies and their results. For trials halted before their scheduled endpoint, ClinicalTrials.gov provides a freeform stopping reason: termination, suspension or withdrawal. A team of researchers previously classified the reasons for 3,125 stopped trials and found that only 10.8% of trials stopped because of a clear negative outcome. By contrast, the majority (54.5%) fell into a set of reasons characterized as neutral in relation to the therapeutic hypothesis, such as patient recruitment or other business or administrative reasons.

Here, we extended that work by training a natural language processing (NLP) model to classify stopping reasons and used this model to classify 28,561 stopped trials. We integrated our classification with evidence associating the drug target and disease from the Open Targets Platform, revealing that trials stopped for lack of efficacy or safety reasons were less supported by genetic evidence. Furthermore, oncology trials involving drugs for which the target gene is constrained in human populations were more likely to stop for safety reasons, whereas drugs with targets with tissue-selective expression were less likely to pose safety risks. These observations confirm and extend previous studies recognizing the value of genetic information and selective expression in target selection.

Results

Interpretable classification of early stoppage reasons

To catalog the reasons behind the withdrawal, termination or suspension of clinical studies, we classified every free-text reason submitted to ClinicalTrials.gov using an NLP classifier. To build a training set for our model, we revisited the manual classification reported in a previous publication of 3,124 stopped trials based on the available submissions to ClinicalTrials.gov in May 2010. The authors of that article classified every study with a maximum of three classes following an ontological structure (Supplementary Table). Each of the classes was also assigned a higher-level category representing the outcome implications for the clinical project. For example, 33.7% of the studies were classified as stopped owing to ‘insufficient enrollment’, a neutral outcome owing to its expected independence from the therapeutic hypothesis. When inspecting submitted reasons belonging to the same curated category, we observed a strong linguistic similarity, as revealed by clustering the cosine similarity of the sentence embeddings (Extended Data). Studies stopped because of reasons linked to lack of efficacy and studies stopped because of futility have a linguistic similarity of 0.98, with both classes manually classified as ‘negative’ outcomes. Based on this clustering, we redefined the classification by merging semantically similar classes represented by low numbers of annotated sentences. Moreover, we added 447 studies that were stopped as a result of the COVID-19 pandemic (Supplementary), resulting in a total of 3,571 studies manually classified into at least one of 17 stop reasons and explained by six different higher-level outcome categories.

By leveraging the consistent language used by the submitters, we fine-tuned the BERT model for the task of clinical trial classification into stop reasons. Overall, the model showed strong predictive power in the cross-validated set (Fmicro = 0.91), performing strongly for the most frequent classes, such as ‘insufficient enrollment’ (F = 0.98) or ‘COVID-19’ (F = 1.00), but demonstrating decreased performance on linguistically complex reasons, such as trials stopped because of another study (F = 0.71) (Supplementary).

To further evaluate the model, we manually curated an additional set of 1,675 stop reasons from randomly selected studies that were not included in the training set. Overall, the performance against the unseen data was lower but comparable to that of the cross-validated model (Fmicro ranging from 0.70 to 0.83 depending on the choice of the annotator) (Supplementary), demonstrating real-world performance and reduced risk of overfitting. Interestingly, the curators demonstrated a relatively low agreement for many classes in which the machine-learning model also showed relatively weak performance, such as studies stopped because of insufficient data or met endpoint.
Reasons reflect operational, clinical and biological constraints

Classification of the 28,561 stopped trials submitted to ClinicalTrials.gov before 27 November 2021 was performed using our NLP model fine-tuned on all the manually curated sentences.  In total, 99% of the trials were classified with at least one of the 15 potential reasons and mapped to one of six different higher-level outcomes. ‘Insufficient enrollment’ remained the most common reason to stop a trial (36.67%), with other reasons before the accrual of any study results also occurring in a large number of studies. A total of 977 trials (3.38%) were classified as stopped because of ‘safety or side effects’, and 2,197 studies (7.6%) were stopped because of ‘negative’ reasons, such as those questioning the efficacy or value (futility). The incidence of each stop reason reflects the purpose of each phase (Extended Data). Studies stopped because of ‘negative’ outcomes more often impacted phase II (odds ratio (OR) = 1.9, P = 2.4 × 10−38) and phase III (OR = 2.6, P = 3.64 × 10−55), whereas studies stopped as a result of ‘safety or side effects’ declined in relative incidence after phase I (OR = 2.4, P = 9.63 × 10−23) (Supplementary). Trials stopped because of the relocation of the study or key staff occurred more than twice as often during early phase I, highlighting the importance of good clinical practices during the foundational stages. Of the studies that provided a stop reason, 48% were indicated for oncology. This large proportion is likely to be the combined result of the specific weight of oncology indications in the aggregated portfolio—27% of drug approvals in 2022—with the reported large incidence of clinical failures in oncology (32%) compared to other indications.



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July 29, 2024

Post-Stroke Cardiovascular risks

Study finds genetic factors key to post-stroke cardiovascular risks

In a recent study published in the journal Stroke, researchers identify genetic and molecular risk factors for subsequent cardiovascular outcomes after incident stroke in an effort to identify potential therapeutic targets to improve patient prognoses.


Identifying the causes of stroke

Stroke is a major global health issue that causes significant disability and mortality, particularly arterial ischemic stroke (AIS). AIS, which is a type of stroke caused by blocked blood flow to the brain, is responsible for up to 85% of stroke cases. AIS arises due to cerebral blood vessel blockage, with modifiable risk factors including hypertension, diabetes, dyslipidemia, atrial fibrillation, obesity, and lifestyle behaviors.

Although genome-wide association studies (GWAS) often focus on incident strokes, studying subsequent events can provide new insights into stroke progression. Further research is crucial to identify genetic and molecular risk factors, establish novel therapeutic targets, and improve prognosis after an initial stroke.

About the study

Data for the current study were obtained from the United Kingdom Biobank (UKB), which includes over 500,000 participants between 40 and 69 years of age, and the Million Veteran Program (MVP), which comprises over 850,000 participants, 8% of whom are women with an average age of 61.9 years. Incident stroke was defined using hospital-linked data for AIS or transient ischemic attack.

Data were standardized to correct collider bias for subsequent stroke, and Slope-Hunter was used. GWAS results for subsequent strokes were compared to incident strokes using replication performance methods.

Multiancestry meta-analyses were conducted, including European-only and across all ancestries from MVP and UKB. Tissue expression analysis was performed using annotation of GWAS and functional mapping.

Mendelian randomization (MR) was used to identify causal relationships between protein abundance, subsequent AIS, and major adverse cardiovascular events (MACE) using protein quantitative trait loci (pQTL) data from the UKB Pharma Proteomics Project. MR estimates were calculated using the Wald ratio method.

Colocalization analysis determined shared genetic factors between traits using the coloc package. Collider bias was evaluated by checking single-nucleotide polymorphism (SNP) associations with stroke incidence and running MR on uncorrected and Slope-Hunter adjusted GWAS results. Significant SNPs and proteins identified from the MR analysis were cross-referenced with known druggable targets.

Study findings

After exclusions based on ancestry and relatedness, 93,422 individuals with incident stroke from the UKB and MVP were included in the study. Taken together, the study cohort comprised 51,929 cases of subsequent major adverse cardiovascular events (MACE) and 45,120 cases of subsequent AIS. Stroke cases were more likely to be older, male, smoke, have hypertension or type 2 diabetes, as well as use antihypertensive and lipid-lowering medications as compared to those without AIS.

GWAS revealed no significant associations in the multi-ancestry meta-analysis for subsequent AIS or MACE. However, two significant genetic variants were identified in specific ancestry analyses, including rs76472767 near the ring finger protein 220 (RNF220) gene in African ancestry for subsequent MACE and rs13294166 near the long intergenic non-protein coding ribonucleic acid (RNA) 1492 (LINC01492) gene in African ancestry for subsequent AIS. These variants were not associated with incident AIS, thus suggesting that the Slope-Hunter correction for collider bias may not have been necessary.

Replication analysis indicated that genetic factors for incident stroke did not fully replicate in subsequent strokes. Of the 91 SNPs associated with incident stroke, 77 replicated in the incidence GWAS, whereas 33 replicated in the subsequent MACE GWAS. This observation suggests distinct genetic etiologies for incident stroke and subsequent MACE.

MR against pQTL data identified six proteins with putative causal effects on incident AIS. These proteins included cystatin E/M (CST6), fibroblast growth factor 5 (FGF5), G-protein-coupled receptor kinase 5 (GPRK5), furin, paired basic amino acid cleaving enzyme (FURIN), matrix metalloproteinase 12 (MMP12), and scavenger receptor class A member 5 (SCARA5). However, none of these proteins were associated with any effects on subsequent MACE.

C-C motif chemokine ligand 27 (CCL27) and tumor necrosis factor receptor superfamily member 14 (TNFRSF14) were associated with causal effects on subsequent MACE. Whereas higher levels of CCL27 were protective, higher levels of TNFRSF14 increased the risk of this condition. Colocalization analysis provided moderate and strong evidence for CCL27 and TNFRSF14, respectively.

Verification using independent pQTL data sets confirmed MR results for five of the nine significant proteins. MR results for CCL27 and TNFRSF14 did not vary significantly across different ancestries; however, the sample sizes for Hispanic and African subgroups were small.

Comparison against potential druggable targets revealed no clinical trials for TNFRSF14 and CCL27. Angiopoietin 1 (ANGPT1), FGF5, furin, MMP12, and tissue factor pathway inhibitor (TFPI), all of which were related to ischemic stroke, were identified as putatively causal in MR for incident stroke.

Conclusions

The current study suggests that CCL27 and TNFRSF14 likely affect stroke progression. Whereas TNFRSF14 influences immune cell survival and plaque destabilization, CCL27 maintains immune homeostasis.

hypertension, high cholesterol, diabetes, obesity, smoking, sedentary lifestyle, family history, age, gender, stress, diet, alcohol consumption, physical inactivity, inflammation, metabolic syndrome, atherosclerosis, arrhythmia, coronary artery disease, blood pressure

#HeartHealth, #CardiovascularRisk, #HighBloodPressure, #CholesterolManagement, #Obesity, #SmokingCessation, #HealthyEating, #PhysicalActivity, #DiabetesAwareness, #StressManagement, #Genetics, #Inflammation, #MetabolicSyndrome, #ArterialPlaque, #BloodSugarControl, #HealthyWeight, #AtrialFibrillation, #CoronaryArteryDisease, #MyocardialInfarction, #Triglycerides

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July 27, 2024

Genetics study on COVID-19

Large genetic study on severe COVID-19

Bonn researchers confirm three other genes for increased risk in addition to the known TLR7 gene


Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in cooperation with other research teams from Germany, the Netherlands, Spain and Italy, investigated a particularly large group of affected individuals. They confirmed the central and already known role of the TLR7 gene in severe courses of the disease in men, but were also able to find evidence for a contribution of the gene in women. In addition, they were able to show that genetic changes in three other genes of the innate immune system contribute to severe COVID-19. The results have now been published in the journal "Human Genetics and Genomics Advances".

Even though the number of severe cases following infection with the SARS-CoV-2 virus has decreased, there is still great interest in understanding why, at the height of the coronavirus pandemic, the infection was severe in some people but not in others. "This is important because it gives us information about the function and reaction of the immune system when it first comes into contact with a pathogen. If we have a better understanding of how severe courses of the disease develop, we can identify people at risk and protect them better or develop targeted therapies. We assume that the findings can be transferred at least in part to future pandemics," says corresponding author Prof. Kerstin Ludwig from the Institute of Human Genetics at the UKB, who is also a member of the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Area TRA "Life and Health" at the University of Bonn.

In addition to many possible reasons such as increased age or pre-existing conditions, some people's own genetic make-up can cause a severe course of the disease. Early work in the pandemic had already identified affected genes, most of which are involved in the innate immune response. The gene with the strongest evidence to date is the TLR7 gene, which was identified as the cause of the disease in two pairs of Dutch brothers with severe cases back in summer 2020. However, it was not yet known to what extent the effect of genetic changes in TLR7 is independent of other non-genetic risk factors, such as increased age or previous illnesses, and whether there are other genes in which so-called mutations significantly increase the risk of severe COVID.

Increased risk of severe Covid-19 lies in three other genes in addition to TLR7


In the recently published study, an international research group led by Prof. Ludwig looked at the gene sequences of 52 candidate genes, including TLR7, in a comparatively large patient sample. Through collaborations with various European groups, the Bonn researchers gained access to DNA material from 1,772 people with severe COVID-19 and 5,347 control individuals with unknown SARS-CoV-2 status from Spain and Italy - i.e. from regions where a very high incidence and high mortality rate was observed, especially at the beginning of the pandemic. All those affected were infected at a time when vaccinations were not yet available - these people therefore had no immune protection and were exposed to the virus virtually "unprepared".

In this large group of people, mutations that render the TLR7 gene non-functional were actually observed significantly more frequently in severely affected COVID-19 patients than in the control group. "This 'enrichment' was even stronger when only those affected people were considered who, due to their age and state of health, would not actually have had a high risk of a severe course. This means that certain mutations in this gene significantly increase the risk of severe progression," says first author and doctoral student at the Bonn Institute of Human Genetics Jannik Boos, who was in charge of the project. In addition to TLR7, the Bonn researchers were also able to identify mutations in the three other genes TBK1, INFAR1 and IFIH1 in the group of severely affected individuals.

Gender-specific differences in COVID-19 progression due to hereditary factors?


The Bonn researchers then took a closer look at TLR7 and found something interesting: the TLR7 gene is located on the X chromosome, of which men only have one copy, but women have two. "So if there is a loss of function of TLR7 on one copy, men no longer have a functioning gene - women, on the other hand, still have a healthy copy, so at least a little bit of functioning TLR7. It was therefore surprising for us that we also found TLR7 mutations more frequently in women with severe COVID-19 courses," says Dr. Axel Schmidt, who is a resident at the Institute of Human Genetics and in the Department of Neuropaediatrics at the UKB and led the study with Prof. Ludwig. Together with Prof. Alexander Hoischen's team from Radboudumc University Hospital in the Netherlands, the Bonn researchers found initial indications that the type of genetic changes is different in women: while in men the mutations lead to the absence of TLR7, in women the "broken" TLR7 versions appear to interact with the "healthy" copies and thus also influence their function. "We assume that TLR7 can also be impaired in women with severe COVID, but presumably via a different biological mechanism," says Ludwig, who is now working with groups from the Immunosensation2 cluster to clarify whether this hypothesis is correct and, if so, what the effects of this mechanism are on the immune system.



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July 26, 2024

Genetic Test

Genetic test eliminates progressive retinal atrophy in English shepherd dogs



Researchers at the University of Cambridge recently published their findings in Genes after identifying the genetic mutation that is causing progressive retinal atrophy (PRA) in English shepherd dogs. PRA is a group of inherited diseases causing progressive degeneration of the light sensitive cells within the back of the eyes. When it comes to PRA in dogs, they are born with normal vision but by the age of 4-5 they go totally blind with no treatment.

According to the release, by identifying the canines carrying this disease before they lose vision, this can be then used as a tool to guide breeding decisions to prevent the passing of the disease onto puppies.1 Historically, owners did not realize their dog had PRA until they were middle-aged, which means it could have been passed on to puppies if they had bred, making this a hard disease to control.

“Once the dog’s eyesight starts to fail there’s no treatment – it will end up totally blind,” said Katherine Stanbury, BSc, PhD, a researcher in the University of Cambridge’s Department of Veterinary Medicine and first author of the report.1 “Now we have a DNA test, there’s no reason why another English Shepherd Dog ever needs to be born with this form of progressive retinal atrophy – it gives breeders a way of totally eliminating the disease.”

The team discovered the genetic mutation causing the disease is recessive, meaning English shepherd dogs can only suffer this blindness if they inherit 2 copies of the gene. For breeding, if a dog only has 1 copy, this makes the dog a carrier and it will not develop PRA but can pass it onto its puppies. If 2 of these carriers are bred together, almost 1 in 4 puppies will be affected. Because dogs are ‘very inbred,’ many individuals are related, giving them a higher chance of being affected by recessive disease when compared to humans.1

The inspiration behind the study came after the team was contacted by a distraught owner of an English shepherd dog, who was diagnosed with PRA. This dog was working as a search and rescue dog but had to retire due to visual deterioration that caused total blindness.


To complete the study, researchers put out a call for DNA samples from other owners or breeders, receiving 6 samples with PRA and 20 without. This gave them enough information to pinpoint the genetic mutation causing PRA using whole genome sequencing. With these findings, PRA can be completely eliminated from English shepherd dog populations quickly.1

The team is offering commercial canine genetic testing services to breeds to help them avoid breeding canines that will develop inherited diseases. These tests will now offer a DNA test for Progressive Retinal Atrophy in English Shepherds that can be bought for £48, a little over 61 USD. Anyone can buy these tests and all that has to be done is pet parents or veterinary professionals will need to swab the inside of the dogs mouth and send it back to the lab for testing.

“An owner won't necessarily notice their dog has got anything wrong with its eyes until it starts bumping into the furniture. Unlike humans who will speak up if their sight isn’t right, dogs just have to get on with things,” explained Cathryn Mellersh, BSc, PhD, University of Cambridge’s Department of Veterinary Medicine, senior author of the report.

“For the price of a decent bag of dog food people can now have their English Shepherd tested for Progressive Retinal Atrophy prior to breeding. It’s about prevention, rather than a cure, and it means a huge amount to the people who breed these dogs. They no longer need to worry about whether the puppies are going to be healthy or are going to develop this horrible disease in a few years’ time,” she concluded.1

This discovery is the 33rd genetic mutation causing an inherited disease in canines that the researchers found, and out of those 33, 23 cause eye diseases. These findings highlight the fact the health and wellbeing of canines has been compromised due to how they have been bred by humans.

The researchers believe that their work with dogs can help provide clarity of the human version of the disease as well as identify targets for gene therapy in the future.


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July 25, 2024

Type of Inherited Blindness in Dogs

Genetic test could eradicate a type of inherited blindness in dogs



A mountain rescue dog whose duties ended after her eyesight failed has helped scientists create a test that could eradicate the genetic eye condition in her breed for good.

Shola the English shepherd has an inherited eye disease called progressive retinal atrophy (PRA) that causes the light-sensitive cells at the back of the eye to deteriorate, eventually leading to blindness.


PRA affects more than 100 dog breeds, can be caused by a number of different genetic variants and has no treatment. For some types, symptoms do not appear until the dog is several years old, by which point they may have passed their genes on to puppies.

Katherine Stanbury, the first author of the research from the University of Cambridge, said Shola was four years old when she began struggling with her vision in dim light.

“She was sent to a veterinary ophthalmologist and they confirmed that she had PRA,” said Stanbury. “And then it turned out her brother also had PRA.”

Stanbury and colleagues have not only identified the genetic variant responsible for the condition in English shepherds but developed a £48 DNA test to reveal whether dogs have none, one or two copies of the variant.

While Stanbury said variants that cause PRA were typically breed-specific, the team will now screen any dog affected by an inherited eye disease for the new variant.

“If it does pop up in another breed, we can monitor that,” she said.

The research began when Shola and her brother were brought to the team’s attention by their concerned breeder.

Writing in the journal Genes, Stanbury and colleagues reported how they carried out whole genome sequencing on the siblings’ DNA but found neither had genetic variants previously associated with PRA, suggesting a different variant was at play.

In a series of analyses using these genomes, as well as data on the genetic makeup of two additional English shepherds with PRA and 22 clear of eye disease, the team identified the variant responsible.

They hope the DNA test will enable owners to identify English shepherds with PRA early and avoid using them for breeding, raising the potential for PRA to be eliminated from the breed.

“You could still breed from a carrier [which has one copy of the variant], as long as you breed with a clear dog,” Stanbury said, adding that was important for genetic variation given the breed is relatively rare, especially in the UK.

She said the team had tested the father of Shola’s offspring, revealing the latter would not develop PRA.

“Two of her daughters have just completed their mountain rescue training with Mountain Rescue England,” said Stanbury. “And one of her sons is a therapy dog.”

Indeed one of the rescue dogs recently saved a man’s life. “[The owners] know that none of those dogs are going to go blind and have all that training be wasted,” Stanbury said.


inherited blindness, dog health, canine genetics, blind dogs, pet health, dog care, canine blindness, pet genetics, animal genetics, veterinary medicine, canine research, dog lovers, dog breeds, puppy care, dog wellness, genetic disorders, vision loss, dog eyes, animal welfare, veterinary science


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Non-vector-borne transmission of lumpy skin disease virus The transmission of “lumpy skin disease virus” (LSDV) has prompted intensive resea...