Category Archives: Genetics

Genetics

Tilapia genetics: a comparative trial between two strains in Brazil – The Fish Site

GenoMar's premium genetic tilapia line - GenoMar 1000 - and a market leading local strain were compared in both pond and cage production systems under commercial conditions in Brazil, during a recent study. The results showed that GenoMar 1000 is superior for growth, survival, and uniformity, growing approximately 30 percent faster than the local strain during the test. With economic analysis suggesting a 31-36 percent annual increase in profits, the results demonstrate GenoMar 1000s potential to enhance productivity, profitability, and sustainability in the Brazilian tilapia industry.

Nile tilapia (Oreochromis niloticus) is one of the most important farmed fish species in the world, and Brazil is one of the leading producers of tilapia globally. In recent years, the Brazilian tilapia industry has experienced a significant increase in production volumes, with annual production surpassing 579,000 tonnes in 2023.

As Brazil continues to develop its tilapia production capabilities whilst maintaining high-quality standards, the country is well-positioned to further increase its share in the global tilapia export market. Despite having vast potential, the comparatively young Brazilian tilapia farming industry continues to encounter significant challenges, with one major hurdle being the limited availability of highly productive and efficient genetic strains. Available local strains of tilapia typically exhibit lower productivity compared to strains that have undergone selective breeding for better growth, survival, and uniformity.

GenoMar Genetics is a leading producer of genetically improved tilapia fingerlings and juveniles under the brands GenoMar and Aquabel. Following 33 generations of selective breeding using state-of-the-art technologies, the GenoMar tilapia strain has been globally recognised for its superior growth, survival, uniformity, fillet yield and carcass quality. Widely regarded as one of the most sought-after tilapia strains in production, the GenoMar strain contributes significantly to enhancing productivity and profitability in the global tilapia industry. Now, GenoMar 1000 - the premium genetic line of the GenoMar strain - previously unavailable in Brazil, has been accessible to farmers since early 2024.

In this article, we have summarised the results of the three major key performance indicators (growth, survival, and uniformity) of GenoMar 1000 compared to a market leading strain of Nile tilapia under commercial pond and cage farming systems in Brazil.

Growth development, final survival and uniformity of GenoMar 1000 compared to a local commercial strain in Brazil. The weights presented are an average of two cages with a 50/50 mix of the two strains (common garden design) GenoMar

We have summarised the growth performances in the trial using three different measurement units:

The fish were harvested 140 days after stocking in both ponds and cages, with GenoMar 1000 outperforming the local strain in terms of growth in both ponds and cages under commercial rearing conditions (Figure 1). In ponds, GenoMar 1000 grew 33 percent faster than the local strain (1,196 g compared to 902 g). In cages, GenoMar 1000 grew 29 percent faster than the local strain (1,350 g compared to 1,046 g).

Growth curves for GenoMar 1000 and the local commercial strain across pond and cage production systems. The x-axis represents the days of culture (DOC), indicating the number of days after stocking in the production systems for common grow-out. GenoMar

The mean average daily gain (ADG) post stocking was higher for GenoMar 1000 compared to the local strain in both ponds and cage production systems (Figure 2). Grown in ponds, GenoMar 1000 grew at a mean daily rate of 8.37 grams, whilst the local strain of tilapia gained an average of 6.35 grams per day during the 140 day grow-out period. When reared in cages, ADG increased slightly for both strains, with GenoMar 1000 growing at an average of 9.49 grams per day, and the local strain gaining 7.37 grams per day, on average.

Simplified, this means that, compared with the local tilapia strain, GenoMar 1000 grew approximately 33 percent faster when reared in ponds, and 29 percent faster when cage reared.

Comparative analysis of average daily gain (ADG) at various body weights for GenoMar 1000 and the local commercial strain in different pond and cage production systems in Brazil GenoMar

GenoMar 1000 reached 1 kg faster than the local strain of tilapia in both pond and cage production systems. GenoMar 1000 reached 1 kg an average of 31.5 and 21.5 days faster than the local strain of tilapia in ponds and cages respectively (Figure 3).

Comparative analysis of number of days to reach 1 kg for GenoMar 1000 and the local commercial strain of tilapia in different ponds and cage production systems. Number of days is calculated from the day of stocking in the production system for common grow-out GenoMar

These findings, from three different growth metrics, demonstrate the significant growth advantages offered by GenoMar 1000, highlighting its potential for enhancing tilapia farming productivity and sustainability.

In addition to growth rate, another key performance indicator for tilapia producers is survival rate, which holds paramount importance for both tilapia hatcheries and grow-out farmers. Thus, we have compared the survival rate of GenoMar 1000 and the local strain for two different time intervals.

Higher survival rates allow hatcheries to produce more tilapia fry and fingerlings without increasing their consumption of resources.GenoMar 1000 tilapia were found to have significantly higher survival in the hatchery stage: both from 0.016 g to 1 g (sex reversal stage) and from 1 g to 10 g (pre-grow-out stage).

During the sex reversal stage, hatchery survival rates for GenoMar 1000 fish and the local tilapia strain were 56 percent and 36 percent, respectively. For the pre-grow-out stage, survival rates increased for both strains, with GenoMar 1000 tilapia surviving at a rate of 87 percent, compared to 78 percent for the local strain. Overall, the total hatchery survival rate for GenoMar 1000 fish was 72 percent higher than that for the local strain of fish.

The fish in the experiment were not vaccinated so that the effect of their genetics on their survival could be observed. Thus, the difference in survival between the two strains is likely due to their different adaptations and abilities to tolerate diseases and general stress during grow-out.

GenoMar 1000 tilapia survived better in cages (p<0.001), while there was no significant difference in survival between the two strains in ponds (Figure 4). This is likely because the ponds were located in a biosecure facility with low disease pressure, whilst the cages were placed in the Lake Palmas, an open environment with less biosecurity.

Survival during grow-out for GenoMar 1000 and the local commercial strain in pond and cage production systems (left), and the mean of pond and cage production systems (right) GenoMar

Streptococcus agalactiae, a common fish pathogen, was detected at the cage site during the experiment, but no treatment was applied. The higher survival of GenoMar 1000 at this site suggests improved resistance to Streptococcosis infection due to specific selection for this trait in every generation since 2016.

Despite being selected in an Asian environment; the trial demonstrates no negative effect on the adaptability and survivability of GenoMar 1000 in Brazilian conditions.On the contrary, the survival of GenoMar 1000 in the cage environment was significantly better.

Cage environments typically carry higher pathogenic pressure and stress levels. GenoMar 1000 has been bred to be more resistant to various economically important pathogens and production environments for a longer period.

Out of ten yolk sac fry from GenoMar 1000, six survived until 1 g (survival rate = 56 percent), compared to four from the local strain (survival rate = 36 percent). The number of fish is rounded to the nearest whole number.

From these survived fingerlings, five from GenoMar 1000 survived the pre-grow-out stage and became juveniles (total survival rate = 48 percent), whilst three from the local commercial strain survived (total survival rate = 28 percent).

Extending this comparison to the grow-out in cages, all five juveniles from GenoMar 1000 survived until harvest (survival rate = 95.2 percent), compared to only two from the local strain (survival rate = 88.9 percent). Further hazard analysis showed that the risk of death during the grow-out stage is significantly decreased by 49 percent in GenoMar 1000, compared to the local strain of tilapia.

To summarise the entire experimental period: Out of ten yolk sac fry from GenoMar 1000, five survived until harvest, compared to two from the local strain (Figure 5). These figures highlight GenoMars commitment to advancing disease resistance and increasing tilapia survival via genetics. These findings validate the efficacy of our innovations in the tilapia breeding programme and demonstrate the potential for sustainable fish farming practices using GenoMar 1000 fingerlings.

Out of ten yolk sac fry of GenoMar 1000, five survived until harvest, compared to two of the local commercial strain GenoMar

Uniformity was measured by calculating the coefficient of variation (CV) of body weight at harvest (BWH). A higher CV means lower uniformity. GenoMar 1000 was found to be more uniform than the local strain of tilapia in both cages and ponds, exhibiting, 23 percent more uniformity than the local strain of tilapia on average (p<0.001).

Figure 6 describes the size variance of simulated populations of Genomar 1000 tilapia and the local strain for their respective CV values, the target weight being 1 kg. A significantly higher proportion of the GenoMar 1000 fish reached the desired harvest weight in both ponds and cage production systems, underscoring its suitability as genetic material for large-scale grow-out operations.

Simulation of a population of 20,000 from each of GenoMar 1000 and the local commercial strain of tilapia to show the size distribution of the fish populations when the targeted average harvest body weight was 1 kg GenoMar

In the preceding sections, we evaluated the growth and survival of the two strains independently. However, to comprehensively assess the effectiveness of stocked juveniles in terms of both growth and biomass conversion into harvestable fish - a vital consideration for farm profitability - we required an index comprising both these traits. In the following sections we have summarised the performance and yield of juveniles using two different metrics:

Performance is calculated as:

This metric essentially calculates the average biomass production (in g) of each stocked juvenile (corrected to the initial stocking weight of the juvenile) per day in the production system.

In the cage production system, the GenoMar 1000 juveniles exhibited an average performance 38 percent higher than the juveniles of the local strain (Figure 7). Each stocked juvenile of the local commercial strain yielded on an average 6.5 g of harvestable biomass per day. Each stocked GenoMar 1000 juvenile surpassed this, producing approximately 2.5 g more, amounting to 9 g of harvested biomass per day.

Similarly, in the pond production system the GenoMar 1000 juveniles showed an average performance that was 33 percent higher than the juveniles of the local strain (Figure 7). Each stocked juvenile of the local strain on average yielded 5.9 g of harvestable biomass per day, whilst the GenoMar 1000 juveniles produced 7.8 g of harvestable biomass per day.

2. Yield (kg harvested/unit of production area)

The yield is calculated as:

This metric essentially calculates the average biomass production (in kg) per unit area (m2 of the surface area of the pond or m3 of the cages in one harvest). The difference in the values for the yield between GenoMar 1000 and the local strain of tilapia is similar to that for the performance (Figure 7). In the pond-based production system, the local commercial strain yielded 1 kg/m2 whilst GenoMar 1000 yielded an additional 0.4 kg for the same unit area. Similarly, in the cage production system the local strain yielded 25.6 kg/m3, whilst the GenoMar 1000 yield exceeded this, yielding 35.4 kg/m3.

Comparison of performance of juveniles (g per fish per day) and yield of juveniles (kg harvested per unit area) in the pond and cage production systems. A higher value for performance and yield indicates better growth, survival, and productivity of the juveniles in the production system GenoMar

Choosing the right genetics is a strategic decision that significantly influences the long-term success of a tilapia production venture. For this, an economic analysis is imperative, providing insights into the monetary benefits for farmers and aiding them in making informed decisions.

Based on the outcomes of this trial, we conducted an economic analysis for both cage and pond production systems, focusing on harvesting tilapia at 1 kg. Both scenarios simulated a stocking of 200,000 tilapia.

Due to the fact that the ponds and cages were shared by fish of both strains, the feed conversion could not be directly measured and compared. Consequently, we used the same feed conversion ratios (FCRs) for both strains within each production system. However, in practice, we have observed that superior growth and increased survival typically correlate with enhanced feed efficiency, ultimately increasing profit margins.

Considering a higher investment in genetically improved fingerlings from GenoMar 1000, a fish farm stocking 200,000 fish in a cage can potentially achieve an annual increase in harvest of 128,895 kg and a profitability increase of R$ 360,834 (equivalent to US $72,167), representing a 36 percent increase in profits. Similarly, in the pond production system, the potential increase in harvest is 122,625 kg, with a profitability increase of R$ 312,664 (equivalent to US $62,533), reflecting a 31 percent increase in profits.

To establish the experimental populations, broodstocks from GenoMar 1000 and the local strain were reproduced within the same facility in Tocantins. This approach aimed to synchronise spawning and minimise environmental variations.

The experimental populations were created using a batch of eggs collected within the same week to ensure similar developmental stages, thus reducing the hatching interval of the larvae to a maximum of five days, mirroring commercial practices (Figure 8).

Experimental design from hatching till individual tagging (pre-grow-out) before stocking for grow-out in ponds and cages GenoMar

At one day post-hatching, 48,180 yolk sac fry from each strain were stocked in two separate hapas within the same pond, receiving identical treatment. This nursery stage lasted 40 days, with sexual reversal during the first 21 days. Subsequently, in the pre-growth stage, 10,000 fingerlings of each strain were randomly collected and stocked in four hapas, two for each strain (with two additional hapas for backup), within the same pond to minimise environmental effects.

Over the next 30 days, these fish were raised under identical water quality conditions and received the same feeding programme until they reached tagging size. Subsequently, 3,000 juveniles from each strain were randomly collected from all hapas, tagged, and transferred to the grow-out stage for a common garden experiment.

GenoMar

Following individual tagging, an equal number of fish from GenoMar 1000 and the local strain of tilapia (selected randomly) were stocked together in two different ponds and two different cages for a blind grow-out. This design ensures that the two groups of fish were reared under the same environmental conditions in each pond and cage (Figure 9).

The 32 m3 cages were stocked to a density of 55 juveniles per m3, with an expected harvest of 70 kg/m3. Comparatively, the 500 m2 ponds were stocked to a density of 2.48 juveniles per m2, with an expected harvest of 3 kg/m2.

Experimental design of the individually tagged fish for blinded common garden grow-out in cages and ponds GenoMar

The cages were positioned in Lake Palmas, where commercial tilapia farming is already in operation. The ponds were located within GenoMars Tocantins facilities. Activities at both locations were synchronised, and a strict feeding programme was followed to simulate commercial production conditions. The grow-out phase was closely monitored until harvest, with individual biometry measurements taken approximately every 25 days.

The grow-out phase of the trial was conducted in ponds at Serra da Tilapia, Monte do Carmo in Tocantins, Brazil (left) and in cages at Lago de Palmas, Lajeado in Tocantins, Brazil (right). GenoMar

A commercial feeding programme was followed during the trial. For the initial six weeks post-hatching, the tilapia was provided with commercial feed comprising 45 percent protein, followed by a switch to a feed containing 36 percent protein from week seven to nine. As the tilapia continued to grow, this diet was further adjusted to one containing 32 percent protein, starting from week ten.

Due to the nature of the trial, it was not possible to differentiate the FCR for GenoMar 1000 and the local strain of tilapia separately. Therefore, the FCR for the combined group is presented in Figure 10 to demonstrate that the FCR rate in the trial was within normal parameters.

Combined feed conversion ratio (FCR) of the production systems at different average body weight of the fish in each cage and pond. The values listed on the right-hand side with inverted triangles represent the predicted FCR when the fish are around 1 kg in each production environment GenoMar

During the common garden grow-out the temperature and dissolved oxygen levels in all cages and ponds were monitored and recorded throughout the experiment and are presented in Figure 11.

The temperature and dissolved oxygen in different ponds and cages during the grow-out period of the experiment GenoMar

A switch to GenoMar 1000 tilapia can be a very beneficial decision for Brazilian tilapia farmers, impacting productivity, profitability, sustainability, and animal welfare:

How does GenoMar 1000 achieve such improved production performance? The answer lies in selective breeding and the use of advanced scientific technology. GenoMar 1000 was developed over many generations by carefully selecting fish with the best growth, survival, and fillet yield traits, resulting in a product that is genetically predisposed to grow quickly and efficiently.

See the original post here:
Tilapia genetics: a comparative trial between two strains in Brazil - The Fish Site

Genetics

New genetic cause of intellectual disability potentially uncovered in ‘junk DNA’ – Livescience.com

Scientists have uncovered a rare genetic cause of intellectual disability in a historically overlooked part of the human genome: so-called junk DNA.

This knowledge could someday help to diagnose some patients with these disorders, the researchers say.

An intellectual disability is a neurodevelopmental disorder that appears during childhood and is characterized by intellectual difficulties that impact people's learning, practical skills and ability to live independently. Such conditions affect approximately 6.5 million Americans.

Factors such as complications during birth can trigger intellectual disabilities. However, in most cases, the disorders have an underlying genetic cause. So far, around 1,500 genes have been linked with various intellectual disabilities but clinicians are still not always able to identify the specific cause of every patient's condition.

Related: Rates of autism diagnosis in children are at an all time high, CDC report suggests

One possible explanation for this gap in knowledge is that previous approaches for reading DNA have only focused on a tiny portion of it. Specifically, they've looked at the roughly 2% of the genome that codes for proteins, known as coding DNA. About 98% of the genome contains DNA that doesn't code for proteins. This DNA was once considered "junk DNA," but scientists are now discovering that it actually performs critical biological functions.

In a new study, published Friday (May 31) in the journal Nature Medicine, scientists used whole-genome sequencing technology to identify a rare genetic mutation within non-coding DNA that seems to contribute to intellectual disability.

Get the worlds most fascinating discoveries delivered straight to your inbox.

The team compared the whole genomes of nearly 5,530 people who have a diagnosed intellectual disability to those of about 46,400 people without the conditions. These data were gathered from the U.K.-based 100,000 Genomes Project.

The researchers discovered that 47 of the people with intellectual disabilities about 0.85% carried mutations in a gene called RNU4-2. They then validated this finding in three additional large, independent genetic databases, bringing the total number of cases to 73.

RNU4-2 doesn't code for proteins but rather for an RNA molecule, a cousin of DNA; RNA's code can either be translated into proteins or stand on its own as a functional molecule. The RNA made by RNU4-2 makes up part of a molecular complex called the spliceosome. The spliceosome helps to refine RNA molecules after their codes are copied down from DNA by "splicing" out certain snippets of the code.

Related: 'Look at all this we don't understand': Study unravels whole new layer of Alzheimer's disease

To further determine the prevalence of this new disorder, the team then launched a separate analysis where they looked at the genomes of another 5,000 people in the U.K. who'd been diagnosed with "neurodevelopmental abnormality." This is a term that refers to any deviation from "normal" in the neurodevelopment of a child.

The team's analysis revealed that, out of those 5,000 people, 21 carried mutations in RNU4-2. That made the mutations the second most common type seen in the overall group, following mutations on the X chromosome known to cause a disorder called Rett syndrome. If changes in RNU4-2 can be confirmed as a cause of intellectual disability, this finding hints that the mutations may contribute significantly to a variety of conditions.

The new study joins a second that also linked RNU4-2 to intellectual disabilities. The research has opened up "an exciting new avenue in ID [intellectual disability] research," Catherine Abbott, a professor of molecular genetics at the University of Edinburgh in the U.K. who was not involved in either study, told Live Science in an email.

"These findings reinforce the idea that ID can often result from mutations that have a cumulative downstream effect on the expression of hundreds of other genes," Abbott said. RNA molecules that don't make proteins often help control the activity of genes, turning them on or off. The findings also stress the importance of sequencing the whole genome rather than just coding DNA, she said.

The scientists behind the new study say the findings could be used to diagnose certain types of intellectual disability.

The team now plans to investigate the precise mechanism by which RNU4-2 causes intellectual disabilities for now, they've only uncovered a strong correlation.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

Go here to see the original:
New genetic cause of intellectual disability potentially uncovered in 'junk DNA' - Livescience.com

Genetics

Scientists identify gene that could lead to resilient ‘pixie’ corn – College of Agriculture and Life Sciences

Dior Kelley, assistant professor, genetics, development and cell biology, and doctoral student Craig L. Cowling, in Kelley's lab. Photo by Whitney Baxter, Iowa State University.

AMES, Iowa A widely found gene in plants has been newly identified as a key transporter of a hormone that influences the size of corn. The discovery offers plant breeders a new tool to develop desirable dwarf varieties that could enhance the crops resilience and profitability.

A team of scientists led by Iowa State University spent years working to pinpoint the functions of the gene ZmPILS6. Now, they have been able to characterize it as an important driver of plant size and architecture, a carrier for an auxin hormone that helps govern growth in roots below ground and shoots, or stalks, above ground. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS) this week.

A hallmark of the current age of science is that we have all this high-quality genome data, whether for corn or humans or other organisms, and now we have the task of figuring out what the genes actually do, said Dior Kelley, assistant professor of genetics, development and cell biology at Iowa State, who led the research team.

The group used reverse genetic screening (from the gene to traits expressed in the plant), combined with other techniques, as they tracked their genes role in corn development. Reverse screens require multiple growing seasons and dont always work, according to Kelley. It took seven years for her group to thoroughly characterize ZmPILS6 and verify it regulates plant growth.

When knocked out of modified, mutant plants, its absence suppressed root lateral formation and plant height. The research has led to a provisional patent for its potential to be used in breeding programs to create short stature corn that is still highly productive.

I think of this as pixie corn, Kelley said. Theres a lot of interest in it for all kinds of reasons, including reduced use of water and nutrients and its ability to withstand high winds.

As they studied ZmPILS6 in corn, the researchers made another curious finding: The gene seemed to have opposite effects on plant growth than a comparable gene in Arabidopsis, a plant often used as a model for research.

This was very unexpected, Kelley said. It illustrates that plant proteins, which have evolved in different contexts, can behave differently. It emphasizes the need to study genes directly within key crops of interest, rather than thinking we understand them based on how they work in other plants.

Kelley gives a lot of the credit for the projects success to a great team of collaborators, especially Craig Cowling, a doctoral student in Kelleys lab who is the first author on the PNAS paper. Craig was the one to really dig in, to confirm that this gene carries the plant hormone auxin, and it absolutely controls size in corn.

This project and being acknowledged as first author on a paper in this important journal has been a little unbelievable, Cowling said. Its been a long journey for me. I never thought I would go to college when I was in high school in Des Moines, so I went into ROTC and then the Marines, where I worked around the world as a technology specialist. When I got out, I wanted to do something different. Thanks to some good mentors, Ive figured out that I love working with and understanding plants.

Kelley calls the new research foundational basic research to understand a gene that impacts numerous, complex growth traits, which evolution has conserved through many plants, from algae to maize. It is also translational, in that it links to genetic resources that can be used to improve breeding programs, she said. This opens up whole new questions and facets of research for my laboratory.

The PNAS papers other co-authors:

This project has been supported by an Agriculture and Food Research Initiative competitive grant through the USDA National Institute of Food and Agriculture and USDA Hatch start-up funding from Iowa State Universitys College of Agriculture and Life Sciences.

See the original post here:
Scientists identify gene that could lead to resilient 'pixie' corn - College of Agriculture and Life Sciences

Genetics

Veritas Genetics at the forefront of genomic screening with new studies presented at the European Society of Human … – PR Newswire

MADRID, May 29, 2024 /PRNewswire/ -- Veritas will have a prominent presence at the upcoming European Society of Human Genetics (ESHG) Congress 2024, to be held in Berlin from June 1 to 4. This year, Veritas will present two innovative studies, reaffirming its commitment to preventive medicine and genomic screening. Additionally, it will highlight its polygenic risk service, myHealthScore, which assesses the genetic risk of common diseases in adults.

The ESHG Congress 2024 is not only a platform for disseminating the most relevant advances in human genetics but also a space for education and knowledge exchange. Plenary sessions, symposia, workshops, and poster presentations will complete an exciting program that covers the latest developments in genetic science.

In this 57th edition of ESHG, Veritas will showcase its comprehensive portfolio in preventive medicine and will participate with a booth (number 240) where its latest advances and services will be exhibited.

Innovative Studies

Veritas will present two abstracts at this edition of ESHG:

This study, led by Dr. Vincenzo Cirigliano (Chief Technical Officer of Veritas) and his team, addresses the first clinical experience in Spain with newborn genomic screening. Saliva, umbilical cord blood, or venous blood samples from 800 newborns were analyzed using exome sequencing.

This abstract, led by Dr. Luis Izquierdo (Chief Medical Officer), details the clinical experience with elective genomic screening in 1300 healthy individuals. The study used Veritas' myGenome test, which analyzes 600 genes based on the ACMG-SF list and ACOG recommendations, along with pharmacogenomics and multifactorial diseases.

Polygenic Risk Assessment

At this year's edition, Veritas will emphasize its comprehensive catalog of preventive genomic medicine, highlighting its innovative polygenic risk service, myHealthScore. This genetic screening test assesses the patient's risk of common multifactorial diseases. The analysis identifies a genetic risk that previously went unnoticed, enabling the detection of a greater number of individuals at risk.

The test results provide insight into the lifetime risk of developing the analyzed diseases, with the goal of establishing preventive strategies and lifestyle changes to help reduce the risk. Diseases

evaluated by myHealthScore include cardiovascular disease, type 2 diabetes, and various types of cancer, such as breast and prostate cancer.

Additionally, polygenic risk complements monogenic risk in a comprehensive assessment of an individual's genetic risk.

AboutVeritas

Veritas applies science and its global resources to bring genomic diagnostics to people, aiming to significantly prolong and improve their lives. Its global portfolio includes services in preventive medicine, perinatal medicine, and genomic diagnostics.

In March 2022, Veritas announced it would join the Letsgetchecked group, a global health solutions company based in Dublin and New York.

In line with its responsibility as a leading biotechnology company, Veritas collaborates with healthcare providers, governments, and local communities to support and expand access to genetic and genomic medicine reliably and affordably worldwide.

Logo - https://mma.prnewswire.com/media/2001152/Veritas_Logo.jpg

SOURCE Veritas

Link:
Veritas Genetics at the forefront of genomic screening with new studies presented at the European Society of Human ... - PR Newswire

Genetics

Alzheimer’s study suggests genetic cause of specific form of disease Harvard Gazette – Harvard Gazette

A recent study published in Nature Medicine offers evidence that genetics may be a direct cause of a specific form of Alzheimers disease and not merely a risk factor. While most patients currently do not have a clearly identified cause of this devastating illness, researchers found that people with two copies of the gene variant APOE4 are at extremely high risk of developing Alzheimers. The finding led them to recommend a new designation that takes this into account, which could lead to up to a fifth of Alzheimers patients being classified as having a genetically caused form of the disease. The shift eventually could lead to earlier diagnosis and treatment and affect the search for therapies. Reisa Sperling, a neurologist at Mass General Brigham and an author of the study, explains the importance of the findings. This interview has been edited for clarity and length.

Your study highlights a new, clearly identified genetic component to Alzheimers disease worthy of a new designation. Could you explain why thats significant?

Designating this form of Alzheimers disease means a group of people who are extremely likely I wont say absolutely, but extremely likely to develop Alzheimers could be treated earlier. This could really have an impact on preventing dementia.

The second thing is theres been an ongoing debate about whether Alzheimers disease has anything to do with amyloid plaques or not. And in this group, they begin to have buildup of amyloid plaques and tau tangles in their late 50s and early 60s, and the likelihood that they will develop symptoms of Alzheimers disease is extremely high. So it creates another link in our understanding of the disease process.

And finally, this is a bridge between the rare forms of genetically determined Alzheimers disease that are 100 percent penetrant and often affect people in their 40s and 50s. Those cases are often considered such a rarity that theyre not representative of Alzheimers disease. So people with two copies of APOE4 are a bit in the middle. This new study really suggests that their biomarkers are similar to what we see in these rare autosomal dominant diseases, and over 90 percent will develop Alzheimers pathology in their brains. It links the rare genetic forms of Alzheimers to what we call sporadic late-onset Alzheimers disease.

Part of this new classification would also make this type of Alzheimers one of the most common genetic disorders in the world. Are there benefits to having it classified that way?

I dont know that Im the best person to opine on that, but I certainly think there may be important reasons. For example, eventually getting insurance coverage for individuals who are below the age of 65 and need rapid evaluation and treatment for Alzheimers disease. Alzheimers disease often doesnt get diagnosed in these individuals because people think theyre too young. Additionally, they may not have insurance coverage for all of the medications required for treatment.

I do think it is important that this is recognized as one of the more common genetic links to Alzheimers disease and leads the way to one day being able to treat people who have a strong family history and genetic predisposition. Then we can really think about being aggressive and treating patients early.

Somehow, we have to turn these findings to instead of being scary for people being a sense of hope.

Weve known for a long time that there is a genetic component to Alzheimers disease. Is this one of the first studies to show such a specific genetic link?

No. As I mentioned there are these rare genes that weve known for more than 20 years that are very specific and cause Alzheimers disease at a much younger age. But this data really suggests that people who have two copies of this particular allele, APOE4, have such a high likelihood of developing Alzheimers disease.

So its not the first genetic link, but it is the first large study that convincingly says having two copies of this gene really increases the likelihood you will have Alzheimers disease. And its a more common gene; these other known genes are very rare. But with APOE4, its estimated that up to 15 percent of Alzheimers patients carry two copies of these alleles (although I will say that estimate is a little different across studies). It is much more common than these very rare autosomal dominant forms.

How common is it in the general population to have two copies of that gene?

Estimated, about 2 percent of the population, so its not that common. People having at least one copy of APOE4 is fairly common. Depending on which part of the world youre from, that can be up to 25 percent. But having two copies is still pretty rare.

There is still so much that we dont know about Alzheimers, but it does seem to be fueled by both genetic and environmental factors. In what ways does this research help push our understanding of the disease overall?

Thats a great question. And for me, this research really does provide support to both camps. One, the likelihood that people with these genes will develop amyloid plaque by the time theyre age 65 is somewhere between 75 and 95 percent. To me that suggests that it is genetically driven.

But there is a variability in the range of when people develop symptoms. And that suggests that there might be environmental or lifestyle factors that can make peoples brains more resilient, or conversely, more vulnerable. This research really supports both ideas that genetics is a major driver in Alzheimers disease, but you can modulate your risk of showing symptoms.

Would it be beneficial for people to know early on if they are carriers of these genes?

At this moment, I do not recommend that people who dont have symptoms get genetic testing or blood-based biomarker testing. I hope that recommendation will change greatly over the next few years.

There are large-scale clinical trials, including the one I run. Were recruiting people who have evidence of amyloid buildup, but dont yet have symptoms, and were recruiting a lot of people with a family history and have copies of APOE4. If that study and other studies like it succeed in treating people before they have symptoms, then I would recommend testing and trying to get treatment as soon as possible.

But we dont have that available right now, and I just think we dont yet know what to do with that information before people have symptoms.

If this new classification did occur, what areas of further research would you be most excited to pursue?

Number one for me is we need to be able to offer treatments to those patients. Right now, theres actually a black-box warning on some currently approved Alzheimers treatments that cautions treating people who have two copies of APOE4 because the risk of side effects is so great. I want to redouble my efforts to make sure we can offer disease-modifying medications in a safe way.

Number two is about the environment. Im quite interested in what it is that modulates whether people get symptoms sooner rather than later, with this buildup of amyloid thats genetically determined. How do we understand what factors were protective? Thats a very important area of research to help us understand what can modulate peoples risk of symptoms in the setting of a very strong genetic predisposition.

We talk about this in the study, but I think its also important to mention that these studies mostly observed white majority populations. And one of the things we desperately need to know is whether these findings are also true in more ethnic and racially diverse populations. There is some evidence that APOE4 might have a slightly different effect on amyloid in populations who come from communities of color.

Similarly, there are slight differences in the sex effects: Women APOE4 carriers have more likelihood of developing symptoms. I think its really important to get more information on representative populations, especially from communities of color, and really help us develop treatments that will work best for everybody.

For people who have Alzheimers or loved ones with Alzheimers, how do these findings offer hope or shed light on the disease?

This is another tool to be able to find people who have Alzheimers disease at an earlier stage and treat them earlier. My dad and my grandfather died of this disease, and Im a clinical neurologist. When I see people with symptoms, I think this is helping us learn about the underlying causes and will help us in accelerating to find good treatments.

I think it will both help the next generation of people who are likely to develop Alzheimers disease, but it will also help us treat people who already have Alzheimers disease symptoms because every little bit of information helps us develop better treatments for all.

I really hope this research doesnt have the effect of just scaring people. I hope it will instead say, These are important clues so that we can treat people earlier and hopefully prevent dementia.

Somehow, we have to turn these findings to instead of being scary for people being a sense of hope. I hope this means we will be able to find people and treat them before they develop symptoms.

By subscribing to this newsletter youre agreeing to our privacy policy

Link:
Alzheimer's study suggests genetic cause of specific form of disease Harvard Gazette - Harvard Gazette

Genetics

Researchers Discover Genetic Underpinnings of Inherited Condition Often Misdiagnosed as Hypothyroidism – InventUM – University of Miami

By: Damian McNamara | May 31, 2024 | 6 min. read| Share Article Summary

Miami cardiologist Cintia Cupermans first-born son screened positive for congenital hypothyroidism in 2002. Her family doctor initially thought it was a false positive. Only one in about 4,000 babies are born with a malfunction of the thyroid gland that produces low levels of thyroid hormone and results in high levels of thyroid stimulating hormone (TSH).

We did some reading ourselves, Dr. Cuperman said. My husband and I are both physicians and we could tell there was something going on that we should be concerned about.

In the first few weeks, before they were referred to an endocrinologist, we were freaking out, Dr. Cuperman added.

When the couple had twins, both children had abnormal thyroid screenings, too. They underwent thyroid hormone treatment for years to avoid the associated health risks, including poor growth and neurologic and cognitive impairment.

Dr. Cupermans children are adults now and recently found out they no longer need therapy. Roy E. Weiss, M.D., Ph.D., professor and chair of the Department of Medicine at the University of Miami Miller School of Medicine, delivered the good news.

I was able to convince them and their doctors not to treat them because otherwise they would have been inappropriately treated with thyroid hormone for the rest of their lives, said Dr. Weiss, also the Rabbi Morris I. Esformes Endowed Chair in Medicine and Endocrinology and the Kathleen & Stanley Glaser Distinguished Chair of Medicine. Their thyroid tests were not consistent with the type of congenital hypothyroidism that needed treatment.

In some cases, newborns screened for congenital hypothyroidism have high TSH but have normal levels of thyroxine hormone. Dr. Cupermans children have this rare, congenital thyroid condition, known as resistance to TSH.

The important clinical implication is making the correct diagnosis, as most of these patients do not need any treatment and are misdiagnosed as hypothyroid, Dr. Weiss said. The misdiagnosis commits them to a lifetime of thyroid hormone treatment and blood tests that are not needed.

Resistance to TSH at birth has been a longstanding mystery, until now.

Dr. Weiss and fellow researchers Samuel Refetoff, M.D., from the University of Chicago Medicine, Helmut Grasberger, M.D., from the University of Michigan, and others found a genetic explanation in an unexpected place. They knew for years the genetic variants related to resistance to TSH were on chromosome 15. Recently they identified genetic changes in the non-coding region of this chromosome, a discovery published in the prestigious journal Nature Genetics.

As we better understand the function of the majority of the genome, the noncoding areas, we will learn more not only about how the thyroid functions but the genetics of other diseases. Dr. Roy Weiss

Importantly, they found how the non-coding regions resulted in the clinical syndrome. A separate team of researchers in Japan made a similar discovery regarding the molecular mechanism behind this condition and published their work in the same issue of the journal.

Their discovery may lead to finding more genetic changes and helping people with other inherited, or Mendelian, genetic conditions. Dr. Weiss and researchers identified noncoding mutations on a short tandem repeat to be the underlying cause of the condition in all affected individuals.

These mutations occur on primate-specific DNA known as the Alu retrotransposon, also found in gorillas. Previous studies have shown that some gorillas also have high-TSH thyroid tests and normal thyroid hormone, which are similar to resistance to TSH.

This is the exciting part, as we dont know how often disease is caused by the 98% of total DNA that is non-coding, Dr. Weiss said.As we better understand the function of the majority of the genome, the noncoding areas, we will learn more not only about how the thyroid functions but the genetics of other diseases.

Most of the genetic discovery took place in Dr. Refetoffs lab, before Dr. Weiss joined the Miller School faculty in 2014. At the time, he and colleagues at the University of Chicago, along with researchers at University of Washington, used the science to identify affected children and families.

One of the families was Dr. Cupermans, whom Dr. Weiss first met in 2012. Two years later, they became his patients in Miami and continue to this day.

As groundbreaking as this genetic discovery is, questions about treatment linger, Dr. Weiss said. But Dr. Cupermans sons are doing well and no longer taking thyroid hormone replacement.

They are super, super healthy, she said. They are both playing soccer in collegeyou know, thriving.

Tags: Division of Endocrinology Diabetes and Metabolism, Dr. Roy Weiss, hypothyroidism, resistance to TSH

See more here:
Researchers Discover Genetic Underpinnings of Inherited Condition Often Misdiagnosed as Hypothyroidism - InventUM - University of Miami

Genetics

Too much or too little: The impact of protein dosage on development – EurekAlert

image:

Model showing the interaction between a portion of the AFF3 protein (in white) and ubiquitin ligase (in green and gold), the protein that regulates its degradation. Amino acids mutated in KINSSHIP syndrome patients are shown as yellow atoms. The ubiquitin ligase amino acids with which they interact are depicted as colored atoms.

Credit: Nicolas Guex UNIL

New research from the University of Lausanne reveals that both the excess and the deficiency of a single protein can lead to severe intellectual deficiencies. The discovery offers critical insights for early diagnosis of a rare developmental disorder.

A team of scientists led by Alexandre Reymond, an expert in human genetics at the Center for Integrative Genomics (CIG) and professor at the Faculty of Biology and Medicine (FBM) of the University of Lausanne (UNIL), presents a major step forward in the detection of a rare genetic disease. For the first time, the authors show that both the accumulation and the deficiency of the so-called AFF3 protein are detrimental to development. The research, published in Genome Medicine, follows on from the groups 2021 discovery of the KINSSHIP syndrome, caused by mutations in the AFF3 gene and resulting in intellectual disability, an increased risk for epilepsy, kidney malformations, and bone deformation in affected children.

Discovery of the genetic cause of KINSSHIP syndrome

KINSSHIP syndrome affects about thirty individuals worldwide. As a result, there are few documented cases and understanding of the disease remains limited, making early and accurate diagnosis challenging. In our previous study we demonstrated that this pathology resulted from an abnormal accumulation of the AFF3 protein. Meanwhile, available genetic data from individuals of the general population suggested that a lack of this same protein could be similarly deleterious", explains Dr. Sissy Bassani, a postdoctoral researcher in Professor Reymond's team and the lead author of the current study.

Large genome database points researchers to a new hypothesis

The geneticists formulated their hypothesis using gnomAD, a database containing genome sequences from several hundred thousand unrelated individuals. By mining the available data for AFF3 variants, the scientists found that loss-of-function mutations in this gene are rare, indicating their likely harmful nature. This implies that this gene plays a critical role and that its loss likely has detrimental consequences for the organism. To test their hypothesis, the authors searched for individuals with only one copy of the gene, instead of the two normally present in the human genome. Collaborating with researchers from nine different countries across Europe and North America, they identified 21 patients with such an anomaly. They all showed similar but less severe symptoms than those of KINSSHIP syndrome patients.

Experiments reveal the developmental impact of AFF3 gene mutations

To demonstrate that both insufficient and excessive amounts of AFF3 are detrimental, the researchers used several different experimental systems: cells of patients, mice, and zebrafish. Artificially decreasing or increasing the protein quantity in zebrafish eggs revealed major developmental defects in the resulting fish embryos. "These results confirm that a precise amount of AFF3 is crucial for proper embryonic development and that mutations affecting its function and/or dosage cause severe malformations", concludes Prof. Reymond.

Impact for prenatal diagnostics

The authors findings are an important advancement for the diagnosis of this rare disorder, as testing for AAF3 mutations during fetal development could improve early detection of these gene defects.

Experimental study

People

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

30-May-2024

Annabelle Tuttle, Houda Zghal Elloumi and Chaofan Zhang are employees of GeneDx and Desiree DeMille works for ARUP Laboratories. James R. Lupski has stock ownership in 23andMe and is a paid consultant for Genome International. Claudia M.B. Carvalho provides consulting service for Ionis Pharmaceu ticals. The other authors have no competing interests to declare.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Read this article:
Too much or too little: The impact of protein dosage on development - EurekAlert

Genetics

Hussman Institute Celebrates National DNA Day with Frost Science Museum – InventUM – University of Miami

More than 2,800 attendees learned about the significance of genomic research.

The day honors the 1953 discovery of the DNA double helix and the completion of the Human Genome Project in 2003. The annual eventalso invites students, educators and the community to learn about and celebrate the impact of the latest advances in genomic research.

Scientists at the Hussman Institute collaborated with Frost Science to provide hands-on experience in the genomics field to the 2,800 museum goers on National DNA day.

This is the second year in a row that we have been able to bring awareness to the community about genetics and ongoing technologies while sparking an interest in science through fun and engaging activities, said Margaret Pericak-Vance, Ph.D., director of the Hussman Institute and the Dr. John T. Macdonald Foundation Professor of Human Genetics Executive Vice Chair. This event stimulates curiosity and introduces kids to genetics, which can be a complicated topic, in a creative way that is easily accessible.

Nine interactive sessions made up the days itinerary as participants embarked on an exhilarating, DNA-based adventure. Sessions let participants create their ownstrandof DNA from candy, unravel the secrets of CRISPR genome editing and extract DNA from strawberries.

Each of our genomes tells a unique story, particularly about where we come from and how that impacts our traits and potentially our health, Dr. Griswold said. I was impressed at the level of interest of the young people at the event and their desire to know about genomics and how it will impact all our futures.

More than just an educational event, National DNA Day was a celebration of community and shared curiosity. Participants of all ages explored the wonders of genomics as the event fostered a sense of camaraderie and connection.

The rest is here:
Hussman Institute Celebrates National DNA Day with Frost Science Museum - InventUM - University of Miami

Genetics

International treaty agreed on handling genetics in patents – Research Professional News

World Intellectual Property Organization signs first new treaty in a decade

A global treaty has been agreed that says applicants for patents involving genetic resources, such as drugs based on a substance produced by a plant, must reveal the origins of those genetic resources.

Patent applicants will be required to disclose the country of origin or source of the genetic resources under the treaty approved by member states of the World Intellectual Property Organization (Wipo) on 24 May.

They must also disclose any basis on Indigenous knowledge.

It is the first Wipo Treaty to be agreed in more than 10 years and also the first that includes genetic resources and Indigenous knowledge.

Best possible compromise

Wipo director general Daren Tang said that the treaty made history in many ways. He said it was showing that the intellectual property system can continue to incentivise innovation while evolving in a more inclusive way, responding to the needs of all countries and their communities.

Brazilian ambassador Guilherme de Aguiar Patriota, who brought the gavel down on the agreement, called the treaty a very carefully balanced outcome.

It constitutes the best possible compromise and a carefully calibrated solution, which seeks to bridge and to balance a variety of interests, some very passionately held and assiduously expressed and defended over the course of decades, he said. Negotiations on the treaty started in 2001.

Member states cheered and applauded as the treaty was agreed on Friday last week. Wipo has 139 member countries, including the United States, China, India,Japan, Germany, France and the UK.

Continued here:
International treaty agreed on handling genetics in patents - Research Professional News

Genetics

Nebraska team identifies new genetic defect impacting cattle morbidity and meat quality – Beef Magazine

Cattle have long been a cornerstone of agriculture, providing us with milk, meat, and various other products that nourish and sustain our communities. Ensuring the cattles health and optimal muscle development is vital when producing high-quality beef. However, various genetic conditions can disrupt muscle metabolism, affecting animals well-being and the quality of the meat they produce.

Researchers at the University of Nebraska Lincoln have discovered a new defect in composite cattle (Simmental, Red Angus, Gelbvieh) that often caused physical collapse when they exercised, with some calves unable to recover. This is an autosomal recessive genetic defect, which means both parents of affected calves must carry one copy of the mutation.

Herd managers at the UNL Gudmundsen Sandhills Laboratory noticed calves from one to six months old lagging behind the herd when moving between pastures. When they increased their pace, calves would collapse and remain at rest for brief periods of time. Pedigree analysis revealed a common herd bull in the sire pedigree of each affected calf. Pedigrees of the dams were unavailable, but heifers were retained as replacements within the herd and were sometimes mated to related bulls. This led to the possibility of inbreeding and suggested that a recessive genetic variant may be responsible for exercise intolerance in these calves.

The herd had undergone routine genotyping as part of the Integrated Beef Systems Initiative Genomics Infrastructure project, enabling a rapid genomic-based approach to finding the causative mutation. A genome-wide association study on 721 animals, including six affected calves, and whole-genome sequencing on two affected calves pinpointed a significant region on chromosome 29. One mutation, not previously identified in this region, waspredicted to truncate the protein product of the genePYGM(glycogen phosphorylase). Due to the expected impact of this variant on the myophosphorylase protein encoded byPYGMand the identification of a previously discoveredPYGMvariant in Charolais cattle, this variant was prioritized for follow-up studies.Next, 381 cattle, including eight affected calves, were genotyped for this variant.In every case, both parents of the affected calf were found to carry one copy of the mutation,and each affected calf had two copies, as we would expect for a recessive genetic variant.

The myophosphorylase encoded byPYGMplays a vital role in breaking down glycogen into usable energy, fueling muscles for sustained activity. Imagine coins (glycogen) collected and saved in a piggy bank (muscle). Myophosphorylase is the key that opens the piggy bank when animals need more energy. If myophosphorylase is absent or not functioning properly, the breakdown of glycogen is compromised, and the energy is not accessible, leading to difficulties in physical activity and muscle damage.

The affected calves showed a significant increase in glycogen stored in skeletal muscle, almost twice as much as the normal and carrier animals. Additionally, the affected calves had elevated creatine kinase before and after forced exercise. This is an essential enzyme that aids in energy production during muscle contraction. Elevated creatine kinase is often a sign of muscle damage or stress. The calves also experienced twitching in their hind limbs and biopsies showed visible signs of muscle damage. Despite these muscle-related issues, microscopic examination of other organs revealed no abnormalities.

The myophosphorylase protein was found in the healthy animal but noticeably missing in the affected calf. This outcome aligned with an additional test, where specific antibodies were used to identify thePYGMprotein in the muscle. The normal calf displayed a positive result with red pigmentation (Figure 1A), while the affected calves distinctly lacked thePYGMprotein (Figure 1B).

Figure 1.(A) Stain for myophosphorylase protein (red color) in a normal calf. (B) Stain for myophosphorylase protein in an affected calf.

The inability to efficiently break down glycogen not only compromises the well-being of the animals but also negatively impacts the quality of the meat they produce. Breaking down stored glycogen efficiently after an animal is harvested is crucial for making high-quality beef. In the absence of myophosphorylase, glycogen breakdown is restricted, hindering the expected decrease in pH. Consequently, the affected calves are labeled as dark-cutters, exhibiting dark-red meat that may have a purplish hue instead of the desired vibrant cherry-red color (Figure 2). This adversely influences consumer perception, shortens the products shelf life, and leads to economic losses. It is important to note that there were no significant disparities in meat quality in the animals carrying only one copy of the mutation.

Figure 2. Ribeye from an affected calf 24 hours after harvest.

Mutations in the same gene in humans result in a disease similar to what is observed in these cattle, termed McArdle disease. Individuals with McArdle disease experience muscle fatigue and weakness during physical activities, making it difficult to complete tasks requiring sustained effort. Affected individuals can live relatively normal lives by adjusting diet and exercise. However, doing the same for cattle, especially those raised for production, is less practical and achievable. Additionally, the economic benefits of managing this condition in cattle is limited due to the impact on product quality.

This recessive condition significantly affects muscle metabolism, raising concerns about animal welfare and introducing economic challenges in raising livestock. These repercussions can affect the survival of animals and, subsequently, the quality of the meat they produce at harvest. While the issue of dark-cutting beef is not new, understanding the underlying genetic factors at play is limited. This study stands out as one of the initial efforts to pinpoint a specific genetic mutation linked to this condition, paving the way for future research into the genetics of dark-cutting beef. Even though animals carrying one copy of this mutation do not show an immediate negative impact on the beef industry, it is imperative to identify them in breeding herds to prevent the production of affected calves. This comprehensive understanding is crucial for the well-being of the animals and the quality assurance of the final product.

This collaborative effort involved UNL students and faculty across disciplines including graduate student researchers Mackenzie Batt, Leila Venzor, Rachel Reith, and Nicolas Herrera, Dr. Jessica Petersen and Dr. Matt Spangler in animal breeding and genetics, Dr. Gary Sullivan in meat science, and Dr. David Steffen with the UNL Veterinary Diagnostic Center. The full paper was published inBMC Genomicsand is available at: https://link.springer.com/article/10.1186/s12864-024-10330-1#citeas.

Original post:
Nebraska team identifies new genetic defect impacting cattle morbidity and meat quality - Beef Magazine