Genetics of Coronary Artery Disease: Discovery, Biology and Clinical Translation !

Genetics

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.

• Coronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.
• Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.
• Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.
• Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.
• Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.
• Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.

Observational epidemiology and translational research efforts have led to significant progress in improving the understanding of the pathophysiology underlying coronary artery disease (CAD). Prevention and treatment strategies developed on the basis of this knowledge led to a >50% decrease in age-adjusted CAD mortality rate in the United States between 1980 and 2000. However, despite these advances, CAD remains the leading global cause of mortality. Current predictions estimate that more than 900,000 individuals in the United States will suffer a myocardial infarction (heart attack) or die of CAD this year.

This review outlines research efforts to understand the genetic drivers of CAD, the role of human genetics in catalysing CAD drug discovery efforts and the promises and challenges of integrating genetic information into routine clinical practice.

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Some Breast Cancers Fail to Respond to Treatments, Why?

Breast Cancer

Most breast cancers are estrogen receptor-positive, meaning that signals received from estrogen, a hormone, promote the growth of the tumors. To stop these cancers from spreading, estrogen inhibitors are usually prescribed. But what happens when tumors develop treatment resistance?

Studies suggest that "approximately 70 percent" of all the breast cancers are estrogen receptor-positive (ER-positive).

These types of cancer are typically treated with drugs — such as tamoxifen and fulvestrant — that either lower the levels of the hormone or inhibit the estrogen receptors to prevent the tumors from spreading. This is known as endocrine therapy.

However, around a third of the people treated with these drugs develop resistance to them, which negatively impacts their chances of survival. The mechanisms that underlie the tumors' resistance to therapy is not well understood and currently poses a major challenge.

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Parents can Influence New Genetic Mutations in Children !

A new study has investigated how mothers and fathers cause new genetic mutations in their children, and how some of these mutations may lead to negative outcomes.

Characteristics that we inherit from our parents - starting with very basic features such as eye color or hair texture - shape not just our identity, but also the state of our health, both earlier and later in life.

That being the case, the study of genetics has become central to understanding who and what we are, as well as how our bodies are likely to develop in time, and how we might respond to internal or external factors.

For instance, recent studies have revealed the importance of genetic factors to conditions including Alzheimer's disease, brain cancer, and diabetes.

Given the importance of understanding the role of genetic factors to our health profile, scientists are constantly striving to decipher the mysteries of the human genome.

Researchers are looking at how the parents' age and sex determine
new genetic mutations in the offspring.

Read more: How do parents influence new genetic mutations in children?

Genetic Mutations in Parents May Increase Risk of ALS in Children

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Source: MSN Health

Gene Editing Could Help Tackle Cancer And Inherited Diseases

Gene editing techniques developed in the last five years could help in the battle against cancer and inherited diseases, a University of Exeter scientist says.

"There is always a risk with this kind of technology and fears about designer babies and we have started having discussions about that so we can understand the consequences and long-term risks," said Dr Westra, of the Environment and Sustainability Institute on the University of Exeter's Penryn Campus in Cornwall. "I think in the coming decades gene editing will become super important, and I think we will see it being used to cure some inherited diseases, to cure cancers, to restore sight to people by transplanting genes. I think it will definitely have massive importance."

On Tuesday, two highly influential academic bodies in the US shook up the scientific world with a report that, for the first time, acknowledged the medical potential of editing inherited genes. The National Academy of Sciences and National Academy of Medicine ruled that gene editing of the human "germline"—eggs, sperm and embryos—should not be seen as a red line in medical research.

Read more: Gene Editing Could Help Tackle Cancer And Inherited Diseases

Source: medicalxpress

Breast Cancer: The Body of Knowledge Grows

Scientists’ understanding of the genetics/genomics of breast cancer continues to grow; a revolution is underway both in terms of categorizing breast cancers and targeting treatment that will be effective in individual cases. New perspectives are being offered on the interpretation of biopsies, too. Here is a round-up of some very recent studies.

Genetic variants alter cells’ response to estrogen

An international study of almost 120,000 women has newly identified five genetic variants affecting risk of breast cancer, all of which are believed to influence how breast cells respond to the female sex hormone estrogen.

Estrogen acts as a trigger, binding to a molecule known as an estrogen receptor in most breast cells and triggering a cascade of signals that cause the cell to behave normally. However, the estrogen receptor is switched off in some cells and these do not respond to the hormone.

Read more: Breast Cancer: The Body of Knowledge Grows

Source: MedicalLaboratoryObserver

Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

By taking a closer look at four-stranded versions of DNA inside the genome of human cells, scientists have discovered some potential new avenues for targeted cancer treatments. They found that the quadruple helix structures occur in DNA regions that control genes, especially cancer genes.

The researchers, from the University of Cambridge in the United Kingdom, report their findings in the journal Nature Genetics.

Targeted cancer therapies are currently the focus of much research and development into new anticancer treatments.

They are an important area of precision medicine - where information about an individual patient's genes and proteins are used to prevent, diagnose, and treat disease.

Read more: Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

The aim of targeted therapy is to attack cancer cells without affecting healthy cells.

Source: MedicalNewsToday

Breast-Feeding May Reduce Asthma Symptoms For At-Risk Infants

A new study provides further evidence of the health benefits of breast-feeding, after finding infants with a genetic susceptibility for asthma development are less likely to experience symptoms of the condition if they are breast-fed.

Asthma is estimated to affect around 8.6 percent of children and adolescents in the United States, making it one of the most common chronic childhood diseases.

Asthma symptoms are the same for children as for adults; these include wheezing, coughing, breathing problems, and chest tightness. However, because children have smaller airways, symptoms may be more severe.

As a result, asthma is the third leading cause of hospital stays and a leading cause of missed school days for children in the U.S.

While the precise causes of asthma remain unclear, studies have suggested the respiratory condition may arise as a result of environmental and genetic factors.

Read more: Breast-Feeding May Reduce Asthma Symptoms For At-Risk Infants

Breast-feeding may reduce respiratory symptoms for children genetically susceptible to asthma
development.

Source: medicalnewstoday

Crohn's disease: Potential treatment to prevent fibrosis uncovered

Scientists from the University of British Columbia in Canada have found a mutation that switches off a hormone receptor, which prevents mice from developing fibrosis. This discovery could lead to potential treatments to prevent fibrosis in people with Crohn's disease.

Inflammatory bowel disease (IBD) - which includes Crohn's disease and ulcerative colitis - affects around 1.6 million people in the United States. Most people are diagnosed with Crohn's disease before age 35, and while these life-long conditions can be treated, there is currently no cure.

Crohn's disease is a long-term condition that causes inflammation to the lining of the digestive system. While the disease can affect any part of the gastrointestinal tract, the most commonly affected areas are the end of the small intestine (the ileum) or the large intestine (colon).

Read more: Crohn's disease: Potential treatment to prevent fibrosis uncovered

Scientists can potentially block complications of fibrosis in Crohn's disease by dampening particular
inflammatory cell types.

Source: medicalnewstoday

Watch: Discovery offers hope for Crohn's disease sufferers

Study Finds Potential New Biomarker For Cancer Patient Prognosis

To treat or not to treat? That is the question researchers at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) hope to answer with a new advance that could help doctors and their cancer patients decide if a particular therapy would be worth pursuing.

Berkeley Lab researchers identified 14 genes regulating genome integrity that were consistently overexpressed in a wide variety of cancers. They then created a scoring system based upon the degree of gene overexpression. For several major types of cancer, including breast and lung cancers, the higher the score, the worse the prognosis. Perhaps more importantly, scores could accurately predict patient response to specific cancer treatments.

The researchers said the findings, to be published Wednesday, Aug. 31, in the journal Nature Communications, could lead to a new biomarker for the early stages of tumor development. The information obtained could help reduce the use of cancer treatments that have a low probability of helping.

Read more: Study Finds Potential New Biomarker For Cancer Patient Prognosis

The centromeres and kinetochores of a chromosome play critical roles during cell division. In mitosis,
microtubule spindle fibers attach to the kinetochores, pulling the chromatids apart. A breakdown in this
process causes chromosome …more

Source: medicalxpress

Vitamin D and Autism: The Missing Link

Causes, Prevention, and Treatment

I first became interested in vitamin D when I learned that it is not a vitamin. Instead, it is the only known substrate of a seco-steroid neuro-hormone that functions, like all steroids, by turning genes on and off.

That means it has as many different mechanisms of action as the genes it regulates. Moreover, vitamin D directly regulates hundreds, if not thousands, of the 21,000 coding genes of the human genome. Genes are responsible for making the proteins and enzymes the human body relies on for normal development and function.

Evidence that vitamin D is involved in the autism epidemic is mounting.

Read more: Vitamin D and Autism: The Missing Link

Source: naturalsolutionsmag

The Genetic Components of Rare Diseases

Techniques for determining which genes or genetic variants are truly detrimental

Last fall, the conclusion of the 1000 Genomes Project revealed 88 million variants in the human genome. What most of them mean for human health is unclear. Of the known associations between a genetic variant and disease, many are still tenuous at best. How can scientists determine which genes or genetic variants are truly detrimental?

Patients with rare diseases are often caught in the crosshairs of this uncertainty. By the time they have their genome, or portions of it, sequenced, they’ve endured countless physician visits and tests. Sequencing provides some hope for an answer, but the process of uncovering causal variants on which to build a treatment plan is still one of painstaking detective work with many false leads. Even variants that are known to be harmful show no effects in some individuals who harbor them, says Adrian Liston, a translational immunologist at the University of Leuven in Belgium who works on disease gene discovery.

Read more: The Genetic Components of Rare Diseases

CROSS COMPARE: Each model organism has its own vocabulary that researchers use to describe
an array of characteristics. The Monarch Initiative has mapped phenotype descriptions used in model
systems to human clinical features. The Initiative’s Exomiser software employs this mapping strategy
to help users better understand human genetic disorders by widening the pool of gene-function
associations. ROBINSON ET AL., GENOME RES, 24:340–48, 2014.

Source: the-scientist

Genetic Testing Before Pregnancy Should Be as Common as Taking Folic Acid

Very few pre-pregnancy checklists include carrier screening as an important health item.

The very first time I had to tell a patient that she was at 25 percent risk of having a baby with cystic fibrosis, she was already 16 weeks pregnant. Only a few months prior, I had graduated and passed my board exam for genetic counseling. This was a "textbook case," as the saying goes. I reviewed the numbers with her and her husband: Odds were in their favor that this pregnancy would not be affected with cystic fibrosis. This couple wanted to know – they needed to know – with more certainty about what to expect. They were older first-time parents, and they agreed that they did not have the financial or emotional means to raise a child with a chronic health issue.

Read more: Genetic Testing Before Pregnancy Should Be as Common as Taking Folic Acid

Carrier screening should be universally offered in the preconception period, one expert argues.

Source: msn.com/en-us/health/medical

Could Regrowing Limbs be a Medical Possibility?

Although the idea of regrowing an amputated limb sounds like science fiction, some experts believe that, one day, it could become science fact. According to recent findings, the answers may be glimpsed in genes that we share with our very distant relatives.

Although humans cannot regrow lost limbs, there is a range of species that can regenerate lost appendages.

These animals include echinoderms, such as starfish and sea cucumbers; amphibians, including the axolotl and newt; and certain fish species.

Although these animals are considered to be far-removed from humanity, because we all evolved from a joint ancestor, we still share large quantities of genetic information.

And, humanity's ability to regenerate has not been completely lost. Although it is now limited to regrowing fingertips and healing wounds, similar genetic mechanisms are thought to be at work.

Read more: Could Regrowing Limbs be a Medical Possibility?

Limb generation may be a long way down the road, but genetic studies give a glimmer of hope.
Axolotls can regrow entire limbs with ease.

Source: medicalnewstoday

Side Effects of Alzheimer's Gene Visible in Child Brain Development

Certain genes increase the risk of developing Alzheimer's disease. The side effects of the most common of these genes, apolipoprotein E, may be evident as early as in childhood, a study finds.

Genetic risks are just one of the factors that may increase or decrease a person's chances of developing Alzheimer's disease (AD), along with age and family history.

While the symptoms of the rarer early-onset AD - representing less than 5 percent of people with the disease - can appear from the age of 30, the symptoms of the more common type, late-onset AD, is apparent over the age of 65.

This study, published in the online issue of Neurology, finds that the effects of the AD gene apolipoprotein E (APOE) may possibly be seen before the age of 20.

Read more: Side Effects of Alzheimer's Gene Visible in Child Brain Development

Studying genes in childhood that increase the risk of developing Alzheimer's disease may possibly
help experts develop ways of delaying the disease.

Source: medicalnewstoday

Breathing New Life into Cystic Fibrosis Genetic Testing

New Research Has Broadened the Number of Clinically Relevant CFTR Gene Mutations.

Imagine yourself suspended a couple of hundred feet below the surface of the ocean. The sheer weight of the immense column of water pushing down on your chest makes each breath a harrowing task. Now picture that your only recourse to collect vital oxygen is to breathe laboriously throw a narrow straw that connects you to the atmosphere above. You slowly draw in air, cautiously trying not to collapse the straw from too forceful of suction—struggling just as much to exhale the expired air. Now repeat the entire cycle for the rest of your life.

If you were able to envision how the immense difficulties of breathing in this manner would be for just a few minutes, let alone your entire life, then you may have a minute sense of what a person afflicted with cystic fibrosis (CF) endures. Gasping for air while thick, sticky mucus lines the pulmonary system, seemingly threatening to drown and suffocate patients with each inhale.

Read more: Breathing New Life into Cystic Fibrosis Genetic Testing

Accurate genetic testing for cystic fibrosis can determine if a patient has the disease and provide
needed information for potential carrier couples, clinical actionability of identified mutations, and
potential severity. [Krishna Kumar/Getty]

Source: genengnews

Prostate Cancer And DNA Mutation: New Connections Revealed

Specific mutations in the DNA of men with metastatic prostate cancer have been shown to play a larger role in the disease than previously thought. Researchers hope that this finding will help change standard therapy guidelines and open the door to drugs currently being used for other cancers.

The new study, published in the New England Journal of Medicine, examined inherited mutations in DNA repair genes.

These gene mutations were already known to occur more frequently in prostate cancer patients than the general population.

However, the present study demonstrated that mutations in DNA repair genes were even more prevalent in people with metastatic prostate cancer, specifically.

Read more: Prostate Cancer And DNA Mutation: New Connections Revealed

Gene mutation research gives a new perspective on prostate cancer.

Source: medicalnewstoday

Tibetans Inherited High-Altitude Gene From Ancient Human

A “superathlete” gene that helps Sherpas and other Tibetans breathe easy at high altitudes was inherited from an ancient species of human. That’s the conclusion of a new study, which finds that the gene variant came from people known as Denisovans, who went extinct soon after they mated with the ancestors of Europeans and Asians about 40,000 years ago. This is the first time a version of a gene acquired from interbreeding with another type of human has been shown to help modern humans adapt to their environment.

Researchers have long wondered how Tibetans live and work at altitudes above 4000 meters, where the limited supply of oxygen makes most people sick. Other high-altitude people, such as Andean highlanders, have adapted to such thin air by adding more oxygen-carrying hemoglobin to their blood. But Tibetans have adapted by having less hemoglobin in their blood; scientists think this trait helps them avoid serious problems, such as clots and strokes caused when the blood thickens with more hemoglobin-laden red blood cells.

Read more: Tibetans Inherited High-Altitude Gene From Ancient Human

Breathing easy. This Tibetan inherited a beneficial high-altitude gene from archaic Denisovan people.

Beijing Genomics Institute

Source: sciencemag

BRCA1 Gene Mutation May Raise Risk of Aggressive Endometrial Cancer

The risk of aggressive serous or serous-like endometrial cancer may be higher for women with a BRCA1 gene mutation, even after undergoing risk-reducing surgery involving the removal of the fallopian tubes and ovaries. This is the finding of a new study published in JAMA Oncology.

However, the study found that a mutated BRCA1 gene did not increase women's overall risk of uterine cancer if they had undergone the risk-reducing procedure, called risk-reducing salpingo-oophorectomy (RRSO).

RRSO is the surgical removal of the fallopian tube and ovaries, and it is sometimes recommended for women who are at high risk of breast or ovarian cancers as a result of BRCA1 or BRCA2 gene mutations.

Read more: BRCA1 Gene Mutation May Raise Risk of Aggressive Endometrial Cancer

Researchers say women with a BRCA1 mutation are at higher risk for aggressive endometrial cancer,
even after undergoing risk-reducing surgery.

Source: medicalnewstoday.

Breast Cancer Treatment Breakthrough After 'Milestone' Genetic Discovery

The latest breast cancer research could lead to more personalized care for patients and help further understanding of the causes of the disease, scientists said.

A study involving people from around the world has been hailed as giving a more complete picture of the changes in DNA in breast cancer, providing potential opportunities for new treatments.

A study of 560 breast cancer genomes, or complete genetic codes, turned up five new genes associated with the disease.

Read more: Breast Cancer Treatment Breakthrough After 'Milestone' Genetic Discovery

Source: IndependentPrintLimited

Breast Cancer: Existing Drug Shows Promise for Prevention in High-Risk Women

Researchers have identified an existing drug that they say has the potential to prevent or delay breast cancer for women at high risk of developing the disease.

In a study published the journal Nature Medicine, researchers reveal how the drug denosumab halted the growth of pre-cancerous cells in breast tissue of women with a faulty BRCA1 gene.

Women with a BRCA1 gene mutation are at significantly greater risk for breast and ovarian cancers; around 55-65 percent of women with such a mutation will develop the disease by the age of 70, according to the National Cancer Institute, compared with 12 percent of those in the general population.

Read more:  Breast Cancer: Existing Drug Shows Promise for Prevention in High-Risk Women

Researchers found the drug denosumab stopped the growth of cells that are a precursor to breast cancer
in women with a BRCA1 gene mutation.

Source: medicalnewstoday