Classes of autism are uncovered with a generative mixture modeling approach leveraging matched phenotypic and genetic data from a large cohort, revealing different genetic programs underlying their phenotypic and clinical traits.
Category: genetics
Study finds genetics shape health impact of leisure versus work physical activity
The benefits of exercise and its positive influence on physical and mental health are well documented, but a new Yale and VA Connecticut study sheds light on the role genetics plays for physical activity, accounting for some of the differences between individuals and showing differences in biology for physical activity at leisure versus physical activity at work and at home.
Using data from the Million Veteran Program (MVP), a genetic biobank run by the U.S. Department of Veterans Affairs, the researchers analyzed genetic influences on leisure, work, and home-time physical activity. They wanted to understand how genetics impacts these three types of physical activity and compare their health benefits.
The study included nearly 190,000 individuals of European ancestry, 27,044 of African ancestry, and 10,263 of Latin-American ancestry. To study the genetics of physical activity during leisure time, the researchers also added data from the UK Biobank, which included about 350,000 individuals.
Research uses AI to find pathologic and genetic basis for worse outcome of endometrial cancer in Black women
Endometrial cancer—in which tumors develop in the inner lining of the uterus—is the most prevalent gynecological cancer in American women, affecting more than 66,000 women a year. Black women are particularly at risk, with an 80% higher mortality rate than other demographic groups and a greater chance of contracting more aggressive cancer subtypes.
Regardless of lifestyle choices and health care equity, studies still show Black women have lower survival rates. A team of Emory researchers wondered: Could that poorer prognosis in Black women be caused by pathologic and genetic differences as well?
“Racism and equitable access to health care certainly play a big role in the increased mortality for populations of color,” says Anant Madabhushi, executive director of the Emory Empathetic AI For Health Institute. “But with endometrial cancer, it may not completely explain the difference in mortality.
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.
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 polygenic risk score (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.