Strategies to accelerate diagnosis and treatment of rare cardiovascular diseases

Yale :The current landscape for patients with rare cardiovascular disease has shifted. Using genome sequencing Yale physician-scientists have begun to elucidate the pathophysiology of genetic disorders and develop treatment guidelines and recommendations. With these advanced diagnostic tools, our team of international experts can offer clinical diagnosis, genetic testing, and risk assessment for patients.

Age of father affects offspring through an epigenetic mechanism

 

Heidelberg/Germany, 5 January 2021 - A team of Japanese scientists has revealed a mechanism associated with an increased risk of behavioural defects among offspring of older fathers in a mouse study, with strong indications similar processes are involved in humans. The researchers examined the link between behavioural defects in mice, specifically animal communication, and lack of DNA methylation—a major process for controlling the expression of genes with a critical role in cell development, ageing and diseases such as cancer. Attachment of methyl groups to the DNA (DNA methylation) is a major epigenetic mechanism that plays an important part in neurological development by ensuring that particular proteins are expressed by their coding genes in specific brain tissues, while being suppressed in tissue where their presence would be damaging.

Extreme stress in childhood is toxic to your DNA

TheConversation: The real danger of separating children from parents is not the psychological stress – it’s the biological time bomb. The screaming and crying, the anguish and desolation is gut-wrenching. But the fallout pales in comparison to the less visible long-term effects that are more sinister and dangerous. Separating children from their parents, in a strange land, among strangers, causes the most extreme life stress a child can experience. And it causes profound and irreversible changes in how their DNA is packaged and which genes are turned on and off in the cells of the body, in organs like the pancreas, the lungs, heart and brain – leading to lifelong changes in its structure and function.

Hundreds of smart genes found

Scimex: Hundreds of genes linked to intelligence have been found by Australian and international researchers. The scientists looked at the DNA of more than 250,000 people and found more than 900 new genes linked to intelligence. They say their works suggests that increased intelligence may protect against both Alzheimer’s disease and ADHD. A second study also identified over 500 genes linked to neuroticism.

Genetic analysis can improve depression therapy

Karolinska Institute: The failure of drugs such as SSRIs, used to treat depression, can be a result of genetic variations in patients. Variations within the gene that encodes the CYP2C19 enzyme results in extreme differences in the levels of escitalopram achieved in patients, according to a new study published in The American Journal of Psychiatry. Prescribing the dose of escitalopram based on a patient’s specific genetic constitution would greatly improve therapeutic outcomes. The study was conducted at Karolinska Institutet in Sweden in association with researchers at Diakonhjemmet Hospital in Oslo, Norway.

The genetics behind being Not Like Daddy

EMBO: A common strategy to create high-yielding plants is hybrid breeding – crossing two different inbred lines to obtain characteristics superior to each parent. However, getting the inbred lines in the first place can be a hassle. Inbred lines consist of genetically uniform individuals and are created through numerous generations of self-crossing. In maize, the use of so-called “haploid inducers” provides a short cut to this cumbersome procedure, allowing to produce inbred lines in just one generation. A study by Laurine Gilles and colleagues, published today in The EMBO Journal, sheds light on the genetics behind haploid induction. “Knowing the molecular identity of haploid induction represents an important breakthrough to fully understand the fertilization process in plants, and hopefully will allow to translate this breeding tool to other species,” said the study’s senior author Dr. Thomas Widiez, an INRA (Institut National de la Recherche Agronomique) researcher at the École Normale Supérieure in Lyon, France.

Hitting the Genetic Jackpot. Exceptional aging is a rarity.

Oregon State University: Your environment — including food choices, exercise habits and sun exposure — contributes the most when it comes to living to an average age. But it is your genes that determine how likely you are to live to an exceptional age. “We define exceptional age as the top 1 percent survival rate in a particular birth year cohort,” says Assistant Professor Harold Bae, who investigated the role of genes on longevity in a recent study published in the Journals of Gerontology: Biological Sciences. “For example, in the New England Centenarian Study, the birth year cohort is 1900. That means that males age 96 and older and females age 100 and older have reached exceptional age.”

How genes get messed up in disease

Harvard: New tool tracks down distant regulators of gene expression, upends expectations. To put things simply, Harvard Medical School researcher Karen Adelman studies DNA “to see how genes get messed up in disease.” Sometimes that means investigating mutations in the genes that make proteins. In sickle cell anemia, for example, a mutated gene builds improperly shaped hemoglobin that sticks together and reduces the ability of red blood cells to carry oxygen.
Adelman’s interest, however, lies in how otherwise normal genes are expressed—turned on or off—in the wrong amounts, at the wrong times or in the wrong tissues.

GIANT study finds rare, but influential, genetic changes related to height

Broad Institute: In the largest, deepest search to date, the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium has uncovered 83 new DNA changes that affect human height. These changes are uncommon or rare, but they have potent effects, with some of them adjusting height by more than 2 cm (almost 8/10 of an inch). The 700,000-plus-person study also found several genes pointing to previously unknown biological pathways involved in skeletal growth. Findings were published online by Nature on February 1.

The National Institutes of Health plans to expand its Encyclopedia of DNA Elements

NIH: The National Institutes of Health (NIH) plans to expand its Encyclopedia of DNA Elements (ENCODE) Project, which is generating a fundamental genomics resource used by many scientists to study human health and disease. Funded by the National Human Genome Research Institute (NHGRI), part of NIH, the ENCODE Project strives to catalog all the genes and regulatory elements - the parts of the genome that control whether genes are active or not - in humans and select model organisms. With four years of additional support, NHGRI builds on a long-standing commitment to developing freely available genomics resources for use by the scientific community.

The Mysterious 98%: Scientists Look to Shine Light on Our Dark Genome

UCSF: After the 2003 completion of the Human Genome Project – which sequenced all 3 billion “letters,” or base pairs, in the human genome – many thought that our DNA would become an open book. But a perplexing problem quickly emerged: although scientists could transcribe the book, they could only interpret a small percentage of it. The mysterious majority – as much as 98 percent – of our DNA do not code for proteins. Much of this “dark matter genome” is thought to be nonfunctional evolutionary leftovers that are just along for the ride. However, hidden among this noncoding DNA are many crucial regulatory elements that control the activity of thousands of genes. What is more, these elements play a major role in diseases such as cancer, heart disease, and autism, and they could hold the key to possible cures.

Super-resolution system reveals mechanics of tiny ‘DNA walker’

Purdue: Researchers have introduced a new type of “super-resolution” microscopy and used it to discover the precise walking mechanism behind tiny structures made of DNA that could find biomedical and industrial applications. The researchers also demonstrated how the “DNA walker” is able to release an anticancer drug, representing a potential new biomedical technology, said Jong Hyun Choi, an associate professor of mechanical engineering at Purdue University.

Diabetes in your DNA? Scientists zero in on the genetic signature of risk

Ann Arbor: Why do some people get Type 2 diabetes, while others who live the same lifestyle never do? For decades, scientists have tried to solve this mystery -- and new research gets them closer to doing so. For decades, scientists have tried to solve this mystery – and have found more than 80 tiny DNA differences that seem to raise the risk of the disease in some people, or protect others from the damagingly high levels of blood sugar that are its hallmark. But no one “Type 2 diabetes signature” has emerged from this search. Now, a team of scientists has reported a discovery that might explain how multiple genetic flaws can lead to the same disease.

Genomic profiling can guide treatment of pediatric brain tumors

Harvard: Precision medicine—in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers—has advanced to the point where it can now impact the care of a majority of children with brain tumors, a new study by investigators at Harvard Medical School and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggests. In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials.

2016's Biggest Medical Science Revolutions

Pennsylvania: In the grand scheme of things, it can seem like progress in science and medicine moves pretty slow. For example, we still aren’t sure what causes premature birth, or why racial disparities exist in certain conditions. And, for all intents and purposes, Alzheimer’s is still a big black box. But in reality, when you put science and medicine under the microscope, you find that a single year can bring big, meaningful gains and exciting advances. So, as we welcome a brand new year, let’s pause to reflect on some of Penn Medicine’s biggest newsmakers from the last 12 months.

Yale team discovers way to pinpoint ‘words’ in genetic book of life

Yale: The development of the embryo into trillions of specialized cells is an intricate genetic dance orchestrated by precisely timed expression of genes. Now a team led by Yale scientists have discovered a way to track the precise bits of RNA that control this crucial process in a living animal. The new assay, tested on the genome of zebra fish, allows scientists to pinpoint function of myriad of signals activated after fertilization. “The problem we have is how to interpret what the book of life is telling us,” said Yale geneticist Antonio Giraldez, senior author of the paper appearing Dec. 26 in the journal Nature Methods. “What we have done is break apart these instructions so we can determine the meaning of individual words.”

Genes that make mice youthful

Nature: Four genes that reprogram adult cells into embryonic-like stem cells can also reverse some signs of ageing. The four genes encode Yamanaka factors, which are essential for embryonic development, but usually cause tumours when expressed long-term in animals. Juan Carlos Izpisua Belmonte at the Salk Institute in La Jolla, California, and his colleagues switched the genes on for two days per week over several weeks in mice that had an ageing disorder called progeria. The animals lived about 30% longer, and showed improvements in tissue healing and other signs of ageing, such as organ failure. In normal aged mice, switching on the genes led to improved recovery from muscle injury and to other signs of youthfulness. The mice did not develop cancer.
The authors link the rejuvenation to epigenetic remodelling — changes in the chemical marks on DNA that do not alter its sequence but influence gene expression.

Many Early Onset Colon Cancers are Caused by Genetic Mutations Passed Through Families

Columbus: One in every six colorectal cancer patients (16 percent) diagnosed under age 50 has at least one inherited genetic mutation that increases his or her cancer risk and many of these mutations could go undetected with the current screening approach, according to initial data from a statewide colorectal cancer screening study conducted at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). In this new analysis, the OSUCCC – James team offers the first detailed report of the prevalence and spectrum of specific mutations in 25 genes associated with inherited (passed down through families) cancer syndromes in an unselected series of colorectal cancer patients. The study includes data from 450 patients with early-onset colorectal cancer recruited from a network of hospitals throughout the state of Ohio.

Can a cancer drug treat a rare cardiac disease?

Yale: About 1 in 2,500 babies born in the United States each year have Noonan syndrome (NS), a genetic disorder that results in severe heart defects, among other symptoms. A mutation in a gene called PTPN11 which encodes for the tyrosine phosphatase Shp2, causes the condition. To identify a potential target for therapy, a team of Yale researchers studied mouse models of the disease.

Historic decision allows UK researchers to trial ‘three person’ babies

Nature: Britain’s fertility regulator has decided to allow the birth of babies from embryos modified to contain three people’s DNA in “certain, specific cases” — making the United Kingdom the first country to explicitly permit the therapy. On 15 December, the UK Human Fertilisation and Embryology Authority (HFEA) announced that it would allow clinics to apply for licences to conduct limited trials of the technique, which aims to prevent mothers from passing down mutations in cellular structures called mitochondria. Last month, the HFEA’s scientific advisory board recommended that trials go ahead.