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Category: genetics – Page 40

Stem cell transplant without toxic preparation successfully treats genetic disease

An antibody treatment developed at Stanford Medicine successfully prepared patients for stem cell transplants without toxic busulfan chemotherapy or radiation, a Phase I clinical trial has shown.

While the researchers tested the protocol on patients with Fanconi anemia, a genetic disease that makes standard stem cell transplant extremely risky, they expect it may also work for patients with other genetic diseases that require stem cell transplants.

“We were able to treat these really fragile patients with a new, innovative regimen that allowed us to reduce the toxicity of the stem cell transplant protocol,” said the study’s co-senior author, Agnieszka Czechowicz, MD, Ph.D., assistant professor of pediatrics.

Finding Human Brain Genes in Duplicated DNA

“Historically, this has been a very challenging problem. People don’t know where to start,” said senior author Megan Dennis, associate director of genomics at the UC Davis Genome Center and associate professor in the Department of Biochemistry and Molecular Medicine and MIND Institute at the University of California, Davis.

In 2022, Dennis was a co-author on a paper describing the first sequence of a complete human genome, known as the ‘telomere to telomere’ reference genome. This reference genome includes the difficult regions that had been left out of the first draft published in 2001 and is now being used to make new discoveries.

Dennis and colleagues used the telomere-to-telomere human genome to identify duplicated genes. Then, they sorted those for genes that are: expressed in the brain; found in all humans, based on sequences from the 1,000 Genomes Project; and conserved, meaning that they did not show much variation among individuals.

They came out with about 250 candidate gene families. Of these, they picked some for further study in an animal model, the zebrafish. By both deleting genes and introducing human-duplicated genes into zebrafish, they showed that at least two of these genes might contribute to features of the human brain: one called GPR89B led to slightly bigger brain size, and another, FRMPD2B, led to altered synapse signaling.

“It’s pretty cool to think that you can use fish to test a human brain trait,” Dennis said.

The dataset in the Cell paper is intended to be a resource for the scientific community, Dennis said. It should make it easier to screen duplicated regions for mutations, for example related to language deficits or autism, that have been missed in previous genome-wide screening.

“It opens up new areas,” Dennis said.

Continue reading “Finding Human Brain Genes in Duplicated DNA” | >

New insights from the 1000 Genomes Project provide most complete view to date of human genetic variation

Completed in 2003, the Human Genome Project gave us the first sequence of the human genome, albeit based on DNA from a small handful of people. Building upon its success, the 1000 Genomes Project was conceived in 2007. The project began with the ambitious aim of sequencing 1,000 human genomes and exceeded it, publishing results gleaned from over 2,500 individuals of varying ancestries in 2015.

UNM Researchers Receive Funding to Launch Clinical Trial of a New Alzheimer’s Vaccine

University of New Mexico researchers have received funding to launch an early-stage clinical trial of a vaccine engineered to clear pathological tau protein from the brains of patients suffering from Alzheimer’s dementia.

The Phase 1a/1b trial, supported in part by a $1 million grant from the Alzheimer’s Association’s Part the Cloud initiative, will test the novel vaccine, which was developed by UNM School of Medicine scientists, said Kiran Bhaskar, PhD, professor in the Departments of Molecular Genetics & Microbiology and Neurology.

“The primary endpoint of this study is safety and tolerability,” he said. “Can these subjects take these vaccinations without any anticipated side effects or adverse events? The second endpoint is the immunogenicity – can they make antibodies to tau?”

MethAgingDB: a comprehensive DNA methylation database for aging biology

Scientific Data — MethAgingDB: a comprehensive DNA methylation database for aging biology. MethAgingDB includes 93 datasets, with 11,474 profiles from 13 distinct human tissues and 1,361 profiles from 9 distinct mouse tissues. The database provides preprocessed DNA methylation data in a consistent matrix format, along with tissue-specific DMSs and DMRs, gene-centric aging insights, and an extensive collection of epigenetic clocks. Together, MethAgingDB is expected to streamline aging-related epigenetic research and support the development of robust, biologically informed aging biomarkers.

Genetic test predicts obesity in childhood

What if we could prevent people from developing obesity? The World Obesity Federation expects more than half the global population to develop overweight or obesity by 2035. However, treatment strategies such as lifestyle change, surgery and medications are not universally available or effective.

By drawing on genetic data from over five million people, an international team of researchers has created a genetic test called a (PGS) that predicts adulthood obesity already in early childhood. This finding could help to identify children and adolescents at higher genetic risk of developing obesity, who could benefit from targeted preventative strategies, such as lifestyle interventions, at a younger age.

“What makes the score so powerful is its ability to predict, before the age of five, whether a child is likely to develop obesity in adulthood, well before other risk factors start to shape their weight later in childhood. Intervening at this point can have a huge impact,” says Assistant Professor Roelof Smit from the NNF Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and lead author of the research published in Nature Medicine.

Genetically modified gut bacteria show promise for combating kidney stones in clinical trial

The human gut microbiome has been shown to impact health in a myriad of ways. The type and abundance of different bacteria can impact everything from the immune system to the nervous system. Now, researchers at Stanford University are taking advantage of the microbiome’s potential for fighting disease by genetically modifying certain bacteria to reduce a substance that causes kidney stones. If scientists are successful at modifying gut bacteria, this can lead to therapeutic treatments for a wide range of diseases.

However, the study, published in Science, shows that this is not a simple task. The researchers used the bacterium Phocaeicola vulgatus, which is already found in the microbiome of humans, and modified it to break down and also to consume porphyran, a nutrient derived from seaweed. The porphyran was used as a way to control the population of Phocaeicola vulgatus by either adding more porphyran or reducing the amount, which should kill off the bacteria due to a lack of food.

The study was made up of three parts: one testing the modified bacteria on rats, one trial with healthy humans and one trial on people with enteric hyperoxaluria (EH). EH is a condition in which the body absorbs too much oxalate from food, leading to and other kidney issues, if not treated.

Inhibitory neurons catch up during brain development

In the study, the researchers also explored how the accelerated maturation of later-born inhibitory neurons is regulated. They identified specific genes involved in this process and uncovered how they control when and to what extent a cell reads and uses different parts of its genetic code. They found that the faster development of later-born inhibitory neurons turns out to be linked to changes in the developmental potential of the precursor cells that generate them—changes which are, in turn, triggered by a reorganization of the so-called ‘chromatin landscape.’

In simple terms, this means that cells adjust the accessibility of certain regions of DNA in the cell nucleus, making key instructions on how and when to develop more readable.

The human brain is made up of billions of nerve cells, or neurons, that communicate with each other in vast, interconnected networks. For the brain to function reliably, there needs to be a fine balance between two types of signals: Excitatory neurons that pass on information and increase activity, and inhibitory neurons that limit activity and prevent other neurons from becoming too active or firing out of control. This balance between excitation and inhibition is essential for a healthy, stable brain.

Inhibitory neurons are generated during brain development through the division of progenitor cells – immature cells not yet specialized but already on the path to becoming neurons. The new study uncovered a surprising feature of brain development based on findings in mice: During this essential process, cells born later in development mature much more quickly than those produced earlier.

“This faster growth helps later-born neurons catch up to those produced earlier, so that by the time all these neurons are incorporated into neural networks, they are at a similar stage of development,” said a research group leader. “This is important, as otherwise, earlier-born neurons—having had more time to form connections—could end up with far more synaptic links than those created later. Without this adjustment, the network could be thrown off balance, and individual cells would have too many or too few connections.”

From telomeres and senescence to integrated longevity medicine: redefining the path to extended healthspan

Despite significant advances in aging research, translating these findings into clinical practice remains a challenge. Aging is a complex, multifactorial process shaped by many factors including genetic, metabolic, and environmental factors. While medical advancements have extended lifespan, healthspan remains constrained by cellular senescence, telomere attrition, and systemic inflammation—core hallmarks of biological aging. However, emerging evidence suggests that telomere dynamic is not inevitable but can be influenced by oxidative stress, lifestyle choices, and metabolic regulation. This review examines how telomere-based biomarkers and metabolic interventions can drive personalized longevity medicine, enabling targeted strategies to delay aging.

Protein aggregation is linked to altered RNA processing

Neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, are devastating and incurable diseases. Although many neurodegenerative diseases are characterized by abnormal protein aggregation in the brain, a limited understanding of whether and how aggregated proteins cause brain cell dysfunction and death represents a major barrier to developing effective treatments.

Inspired by similar approaches in cardiovascular disease and cancer, the researchers focused on rare genetic forms of neurodegeneration as a powerful way to uncover fundamental mechanisms tying protein aggregation to brain disease. Thier work unexpectedly linked protein aggregation in genetic forms of neurodegeneration to disrupted processing of transfer RNAs (tRNAs), revealing an important mechanism that might be therapeutically targeted in these disorders.

The authors were interested in genetic forms of neurodegeneration caused by GGC trinucleotide repeat expansions (DNA sequence mutations caused by copying this 3-letter sequence too many times in a row). These mutations produce aggregation-prone proteins with long stretches of a single repeated amino acid (glycine).

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