2014 NCAS Philip J. Klass Award Presentation to Steven Salzberg
On November 15, the 2014 NCAS Philip J. Klass Award for outstanding contributions in promoting critical thinking and scientific understanding was presented t...
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2014 NCAS Philip J. Klass Award Presentation to Steven Salzberg - Video
Genes arent all that, whats really important is the environmental regulation of these genes
This crap. Okay, so a raccoon can become a human with a proper environment?
If not, then what is this guy saying? Is he saying 100% of all differences between all individual humans are down to environmental effects? 90%? 80%?
Or is he just saying that differences between big groups of humans (dont dare call them races) are 99.999% down to environment? Individuals can differ in the hard code, groups of individuals can differ, but if the groups correspond with the classical races, then the hard code cannot differ in anything but that which is labeled by people today as unimportant, things like skin color.
The silly thing is that epigenetic effects are ALREADY CAPTURED in old heritability estimates. Theyre just put in the bucket labeled environmentality.
Its interesting to learn about the mechanisms by which environmentality occurs, but this guy heavily implies that this mechanism increases the importance of environment above what was previously considered.
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PUBLIC RELEASE DATE:
12-Dec-2014
Contact: Steve Yozwiak syozwiak@tgen.org 602-343-8704 The Translational Genomics Research Institute
PHOENIX, Ariz. -- Dec. 12, 2014 -- Using a basic genetic difference between men and women, the Translational Genomics Research Institute (TGen) has uncovered a way to track down the source of a neurological disorder in a young girl.
TGen's discovery relies on a simple genetic fact: Men have one X and one Y chromosome, while women have two X chromosomes. This women-only factor was leveraged by TGen investigators to develop a highly accurate method of tracking down a previously unrecognized disorder of the X-chromosome.
The study of a pre-teen girl, who went years with an undiagnosed neurobehavioral condition, was published today in the scientific journal PLOS ONE.
TGen's findings were made within its Dorrance Center for Rare Childhood Disorders, where investigators and clinicians apply the latest tools of genomic medicine to provide answers for parents seeking to identify the disease or disorder affecting their child.
The scientists sequenced, or spelled out in order, the complete genetic codes of DNA and RNA of the girl. Because girls inherit an X chromosome from each of their parents (boys inherit a Y chromosome from their father), they also sequenced her mother and father. On average, about half of all X chromosomes active in a female come from the mother and the other half from the father.
"We now have the tools to significantly accelerate the diagnostic process, reducing the need for children to undergo multiple tests that can be emotionally and physically taxing for the entire family," said Dr. David Craig, TGen's Deputy Director of Bioinformatics, Co-Director of the Dorrance Center and the paper's senior author.
Sequencing would reveal the proportion of X chromosomes, and if disproportionate, whether the more abundant of the two were damaged in some way, which often leads to X-linked genetic conditions.
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New TGen test uses the unique genetics of women to uncover neurologic disorders
The Future of Genetic Medicine - Maureen Turner
With no background in biology or genetics, ease into an understanding of the state of genetics and issues in society with enough familiarity to discuss news ...
By: Olli SFSU
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The Future of Genetic Medicine - Maureen Turner - Video
A single of the well-known conventional Chinese medicines is acupressure. This historical Chinese method employs twelve meridians or energy factors in the human entire body to take care of it from discomfort. By implementing delicate but firm stress by way of the fingers it can achieve out to these meridians which are scattered all above the physique from the fingertips that are connected to the mind and the organs which are harmoniously related to a specific meridian.
While acupuncture makes use of slender needles to promote the twelve meridian factors, acupressure utilizes the palms to get to them out making use of stress. The two of these extensively approved Chinese medications use the exact same energy points or meridians. Lots of scientific info abounds that help the belief that acupuncture is genuinely efficient.
A lot of have verified that acupressure has been an successful method to take care of tension triggered health issues. With the use of the human hand, it has the electricity and sensitivity to link and promote the meridian details to experience a new vitality on the human entire body. It views the complete human man or woman as a total composed of a physique, mind, and spirit and with thoughts. This method allows it to loosen up the human body from muscular rigidity and ignites the balancing of the body to make it appreciate a overall health feeling.
Acupressure has been recognized to supply the client to be relieved of pressure and stress. It relaxes the human body and head soon after every session. It also raises blood circulation by aiding it is cleansing the physique of harmful toxins. It promotes fast healing from accidents by means of elevated power ranges right after stimulating the energy details. It is likewise a excellent help in decreasing pains during labor on ladies.
With these several wellness positive aspects derived from acupressure, it is worthwhile to be aware that fingers are the only medium employed. Nevertheless, only trained and expert therapist is experienced to give the greatest results. It is a ability possessed only by certified therapist to pinpoint the spot to be pressed on the surface of the physique. Failure to recognize the specific details would end result to non stimulation of the normal self therapeutic attributes of the entire body. It would be fruitless that soon after each session absolutely nothing helpful is seasoned by the affected person if completed by unqualified therapist in acupressure.
Particularly, acupressure has been a excellent reduction for neck pain, complications, eyestrain, sinus problems, muscles and backaches, arthritis and a very good rigidity buster. It helps the body to regain more robust resistance towards sickness therefore promoting the standard wellness of the individual that avails it.
Going more than the info about Chinese medicines, it is pointed out that there are far more than 8 hundred crucial energy points alongside the primary twelve meridians in the human body. These are connected that are scattered from the heels up to the head with concentrations on each sides of the spinal column. Each vitality position has its own therapeutic stimulation to the linked organ. In making use of acupressure, therapeutic treatment method is relayed on the specific organ influenced by stimulating that important stage together the meridians.
However, there are critical guides in choosing acupressure therapeutic massage. A single is to consult your medical professional if you have health issues prior to undergoing this therapeutic massage. Second, if you have certified to get this massage, be sure to consume tons of warm water after the session to facilitate the excretion of harmful toxins from your human body.
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PUBLIC RELEASE DATE:
10-Dec-2014
Contact: Shawna Williams shawna@jhmi.edu 410-955-8236 Johns Hopkins Medicine @HopkinsMedicine
While many different combinations of genetic traits can cause autism, brains affected by autism share a pattern of ramped-up immune responses, an analysis of data from autopsied human brains reveals. The study, a collaborative effort between Johns Hopkins and the University of Alabama at Birmingham, included data from 72 autism and control brains. It will be published online Dec. 10 in the journal Nature Communications.
"There are many different ways of getting autism, but we found that they all have the same downstream effect," says Dan Arking, Ph.D. , an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. "What we don't know is whether this immune response is making things better in the short term and worse in the long term."
The causes of autism, also known as autistic spectrum disorder, remain largely unknown and are a frequent research topic for geneticists and neuroscientists. But Arking had noticed that for autism, studies of whether and how much genes were being used -- known as gene expression -- had thus far involved too little data to draw many useful conclusions. That's because unlike a genetic test, which can be done using nearly any cells in the body, gene expression testing has to be performed on the specific tissue of interest -- in this case, brains that could only be obtained through autopsies.
To combat this problem, Arking and his colleagues analyzed gene expression in samples from two different tissue banks, comparing gene expression in people with autism to that in controls without the condition. All told, they analyzed data from 104 brain samples from 72 individuals -- the largest data set so far for a study of gene expression in autism.
Previous studies had identified autism-associated abnormalities in cells that support neurons in the brain and spinal cord. In this study, Arking says, the research team was able to narrow in on a specific type of support cell known as a microglial cell, which polices the brain for pathogens and other threats. In the autism brains, the microglia appeared to be perpetually activated, with their genes for inflammation responses turned on. "This type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits," says Andrew West, Ph.D., an associate professor of neurology at the University of Alabama at Birmingham who was involved in the study.
Arking notes that, given the known genetic contributors to autism, inflammation is unlikely to be its root cause. Rather, he says, "This is a downstream consequence of upstream gene mutation." The next step, he says, would be to find out whether treating the inflammation could ameliorate symptoms of autism.
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Brain inflammation a hallmark of autism, large-scale analysis shows
TIME Health medicine Genetic Screening Saved This Babys Life Researchers say sequencing genomes can lead to quicker diagnoses and effective treatments for more than half of children affected by brain disorders
Mya Burkhart was only six months old when she went into cardiac arrest. Fortunately, she was in the hospital when it happened, brought there by her parents because she had trouble breathing. It was her eighth or ninth visit to the emergency room for her respiratory problems, but each time the doctors had sent the Burkharts home with more questions than answers.
Mya wasnt developing at the normal rate. She couldnt lift her head and wasnt responding to people and things around her. Doctors thought she might have a muscle disorder, but her other symptoms did not fit with that diagnosis.
After her heart scare, Mya spent three weeks, including her first Christmas, in the ICU on a ventilator. I couldnt pick her up or anything, says her mother Holly. Still unable to solve the mystery of what was ailing her, the doctors finally suggested she have her genome tested. Maybe, they hoped, her DNA would offer some clues about why she wasnt growing normally.
MORE: The DNA Dilemma: A Test That Could Change Your Life
Holly knew the test was still in the research stages, and that there was a chance that even it might not yield any more answers about her daughters condition. At that point, I just wanted to try anything to find out what was wrong with her, she says. It boiled down to balancing a chance that their baby would live or die.
Genetic screening, especially whole-genome screening in which people can learn about their possible risk for certain diseases, remains controversial, since the information is neither definitive nor always accurate. In most cases, genes can only predict, with a limited amount of certainty, whether a disease such as breast cancer or Alzheimers looms in a persons future. As the Food and Drug Administration (FDA) contemplates the merits and efficacy of such screening, some doctors and researchers are using it with great success, according to a new study published in the journal Science Translational Medicine.
Researchers at Childrens Mercy Hospital in Kansas City, where Mya was treated, say that for 100 families, including the Burkharts, with children affected by either unknown disorders or brain abnormalities, genome screening helped 45% receive a new diagnosis, and guided 55% to a different treatment for their childs disorder. Of the 100 families, 85 had been going from doctor to doctor in search of a diagnosis for an average of six and a half years.
I was surprised by how many cases we found where a specific intervention can make a difference, says Sarah Soden from the Center for Pediatric Genomic Medicine at Childrens Mercy and the studys lead author. For me its compelling enough to push the envelope and get younger kids diagnosed.
MORE: Faster DNA Testing Helps Diagnose Disease in NICU Babies
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Newswise For a small percentage of cancer patients, treatment aimed at curing the disease leads to a form of leukemia with a poor prognosis. Conventional thinking goes that chemotherapy and radiation therapy induce a barrage of damaging genetic mutations that kill cancer cells yet inadvertently spur the development of acute myeloid leukemia (AML), a blood cancer.
But a new study at Washington University School of Medicine in St. Louis challenges the view that cancer treatment in itself is a direct cause of what is known as therapy-related AML.
Rather, the research suggests, mutations in a well-known cancer gene, P53, can accumulate in blood stem cells as a person ages, years before a cancer diagnosis. If and when cancer develops, these mutated cells are more resistant to treatment and multiply at an accelerated pace after exposure to chemotherapy or radiation therapy, which then can lead to AML, the study indicates.
The teams findings, reported Dec. 8 in the journal Nature, open new avenues for research to predict which patients are at risk of developing therapy-related AML and to find ways to prevent it.
About 18,000 cases of AML are diagnosed in the United States each year, with about 2,000 triggered by previous exposure to chemotherapy or radiation therapy. Therapy-related AML is almost always fatal, even with aggressive treatment.
Until now, weve really understood very little about therapy-related AML and why it is so difficult to treat, said corresponding author Daniel Link, MD, a hematologist/oncologist at Siteman Cancer Center at Washington University and Barnes-Jewish Hospital. This gives us some important clues for further studies aimed at treatment and prevention.
The researchers initially sequenced the genomes of 22 cases of therapy-related AML, finding that those patients had similar numbers and types of genetic mutations in their leukemia cells as other patients who developed AML without exposure to chemotherapy or radiation therapy, an indication that cancer treatment does not cause widespread DNA damage.
This is contrary to what physicians and scientists have long accepted as fact, said senior author Richard K. Wilson, PhD, director of The Genome Institute at Washington University. It led us to consider a novel hypothesis: P53 mutations accumulate randomly as part of the aging process and are present in blood stem cells long before a patient is diagnosed with therapy-related AML.
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Genetic Errors Linked to Aging Underlie Leukemia That Develops After Cancer Treatment
PUBLIC RELEASE DATE:
7-Dec-2014
Contact: Glenna Picton picton@bcm.edu 713-798-7973 Baylor College of Medicine @bcmhouston
HOUSTON - (Dec. 7, 2014) - An international consortium of researchers led by Baylor College of Medicine has identified for the first time a gene associated with familial glioma (brain tumors that appear in two or more members of the same family) providing new support that certain people may be genetically predisposed to the disease.
"It is widely thought amongst the clinical community that there is no association between family history and development of glioma. Because we know very little about the contributing genetic factors, when cases occur in two or more family members, it is viewed as coincidental," said Dr. Melissa Bondy, associate director of cancer prevention and population sciences at the NCI-designated Dan L. Duncan Cancer Center at Baylor College of Medicine and lead author of the report that appears in the Journal of the National Cancer Institute today. "By understanding more about the genetic link, we hope that one day we can improve treatments and preventive strategies for those with a family history of glioma."
Bondy estimates that approximately five percent of brain tumors run in families.
The study was conducted through the Gliogene Consortium, a collaborative group of familial brain tumor researchers from around the world, which is primarily supported with funding from the National Cancer Institute.
"I have been researching familial glioma for nearly 30 years, and this study is really the first time we have had a hit when it comes to identifying a gene that is potentially associated with predisposition to the disease," said Bondy, principal investigator of the Gliogene Consortium.
The Gliogene Consortium recruited 435 families in which glioma occurred from 14 centers in the United States, Sweden, Denmark, The United Kingdom and Israel. The recruitment occurred between 2007 and 2011 while Bondy was on faculty at The University of Texas MD Anderson Cancer Center. She joined the Baylor faculty in September 2011.
Once at Baylor, Bondy collaborated with experts in the College's Human Genome Sequencing Center to advance research of the genetics of the disease.
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New study identifies first gene associated with familial glioma
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Newswise Genetic mutations may cause more cases of amyotrophic lateral sclerosis (ALS) than scientists previously had realized, according to researchers at Washington University School of Medicine in St. Louis and Cedars-Sinai Medical Center in Los Angeles. The scientists also showed that the number of mutated genes influences the age when the fatal paralyzing disorder first appears.
ALS, also known as Lou Gehrigs disease, destroys the nerve cells that control muscles, leading to loss of mobility, difficulty breathing and swallowing, and eventually paralysis and death. Understanding the many ways genes contribute to ALS helps scientists seek new treatments.
The study appears online in Annals of Neurology.
Scientists have linked mutations in more than 30 genes to ALS. Alone or in combination, mutations in any of these genes can cause the disease in family members who inherit them.
Roughly 90 percent of patients with ALS have no family history of the disease, and their condition is referred to as sporadic ALS. Scientists had thought mutations contributed to barely more than one in every 10 cases of sporadic ALS.
But researchers recently started to suspect that patients with sporadic ALS carry mutations in the 30 genes linked to ALS more often than previously thought. The new study is among the first to prove this suspicion correct.
To our surprise, we found that 26 percent of sporadic ALS patients had potential mutations in one of the known ALS genes we analyzed, said co-senior author Matthew Harms, MD, assistant professor of neurology at Washington University. This suggests that mutations may be contributing to significantly more ALS cases.
The scientists used a sequencing technique devised at Washington University to look at 17 known ALS genes in the DNA of 391 patients with ALS. Like the overall ALS patient population, 90 percent of the patients had no family history of disease.
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Genetic Errors Linked to More ALS Cases Than Scientists Had Thought
PUBLIC RELEASE DATE:
5-Dec-2014
Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center @cedarssinai
LOS ANGELES (Dec. 4, 2014) - Genetics may play a larger role in causing Lou Gehrig's disease than previously believed, potentially accounting for more than one-third of all cases, according to one of the most comprehensive genetic studies to date of patients who suffer from the condition also known as amyotrophic lateral sclerosis, or ALS.
The study, conducted by investigators at Cedars-Sinai and Washington University in St. Louis, also showed that patients with defects in two or more ALS-associated genes experience disease onset about 10 years earlier than patients with single-gene mutations.
"These findings shed new light on the genetic origins of ALS, especially in patients who had no prior family history of the disease," said Robert H. Baloh, MD, PhD, director of neuromuscular medicine in the Department of Neurology and director of the ALS Program at Cedars-Sinai. Baloh is senior author of the study, published online in Annals of Neurology.
Typically, researchers classify 90 percent of ALS cases as "sporadic," meaning they occur in patients without a family history of the disease. In their study, however, the researchers found a significant degree of genetic involvement in patients with no family history. Examining DNA from 391 individuals, they identified numerous new or very rare ALS gene mutations in such people. Added to the 10 percent of cases already known to be genetic because of family history, the study suggested that more than one-third of all ALS could be genetic in origin.
Baloh said the presence of the new and rare mutations, found among 17 genes already known to be associated with ALS, does not necessarily mean they all cause the disease. But they are considered likely suspects - especially in combination. ALS often is caused by well-known defects in single genes, but recent studies have suggested that some cases could be brought on by the simultaneous occurrence of two or more "lesser" genetic defects. In theory, each mutation alone might be tolerated without initiating disease, but in combination they exceed the threshold required for disease development.
This study strengthens that possibility: Fifteen patients - nine of whom had no previous family history of ALS - had mutations in two or more ALS-associated genes. The research also takes an important next step, showing that multiple genetic defects can influence the way disease manifests in individual patients. Those with mutations in two or more genes had onset about 10 years earlier than those with defects in only one gene.
Matthew B. Harms, MD, assistant professor of neurology at Washington University and co-corresponding author of the article, said that unknown factors still accounted for the majority of ALS cases.
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Study shows more patients with ALS have genetic origin than previously thought
Genetics may play a larger role in causing Lou Gehrig's disease than previously believed, potentially accounting for more than one-third of all cases, according to one of the most comprehensive genetic studies to date of patients who suffer from the condition also known as amyotrophic lateral sclerosis, or ALS.
The study, conducted by investigators at Cedars-Sinai and Washington University in St. Louis, also showed that patients with defects in two or more ALS-associated genes experience disease onset about 10 years earlier than patients with single-gene mutations.
"These findings shed new light on the genetic origins of ALS, especially in patients who had no prior family history of the disease," said Robert H. Baloh, MD, PhD, director of neuromuscular medicine in the Department of Neurology and director of the ALS Program at Cedars-Sinai. Baloh is senior author of the study, published online in Annals of Neurology.
Typically, researchers classify 90 percent of ALS cases as "sporadic," meaning they occur in patients without a family history of the disease. In their study, however, the researchers found a significant degree of genetic involvement in patients with no family history. Examining DNA from 391 individuals, they identified numerous new or very rare ALS gene mutations in such people. Added to the 10 percent of cases already known to be genetic because of family history, the study suggested that more than one-third of all ALS could be genetic in origin.
Baloh said the presence of the new and rare mutations, found among 17 genes already known to be associated with ALS, does not necessarily mean they all cause the disease. But they are considered likely suspects -- especially in combination. ALS often is caused by well-known defects in single genes, but recent studies have suggested that some cases could be brought on by the simultaneous occurrence of two or more "lesser" genetic defects. In theory, each mutation alone might be tolerated without initiating disease, but in combination they exceed the threshold required for disease development.
This study strengthens that possibility: Fifteen patients -- nine of whom had no previous family history of ALS -- had mutations in two or more ALS-associated genes. The research also takes an important next step, showing that multiple genetic defects can influence the way disease manifests in individual patients. Those with mutations in two or more genes had onset about 10 years earlier than those with defects in only one gene.
Matthew B. Harms, MD, assistant professor of neurology at Washington University and co-corresponding author of the article, said that unknown factors still accounted for the majority of ALS cases.
"This tells us that more research is needed to identify other genes that influence ALS risk, and that ultimately, individuals may have more than one gene contributing toward developing disease," Harms said.
ALS is an incurable, virtually untreatable neurodegenerative disease that attacks motor neurons -- nerve cells responsible for muscle function -- in the brain and spinal cord. It causes progressive weakness and eventual failure of muscles throughout the body; patients typically survive three to five years after onset.
Investigators in this study used new-generation technology that quickly and efficiently determines the organizational structure of large numbers of genes. They expect this and similar research to usher in personalized medicine in ALS that will allow healthcare teams to analyze a patient's entire genetic makeup and deliver gene-specific therapies to correct detected defects. Cedars-Sinai researchers recently conducted a disease-in-a-dish study with cells from patients with defects in a gene that commonly causes ALS. Using small segments of genetic material to target the defects, they showed that this type of gene therapy can improve neurons from patients with the disease.
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More patients with Lou Gehrig's disease have genetic origin than previously thought
THURSDAY, Dec. 4, 2014 (HealthDay News) -- Many American parents would be interested in having their newborn baby undergo in-depth genetic screening to learn about potential health risks, a new study reveals.
Newborns currently get a blood test to screen for at least 30 heritable, treatable conditions. But in-depth genetic screening, known as genomic testing, has the potential to provide more comprehensive personal information, according to the Boston-based researchers.
The researchers surveyed 514 parents within 48 hours of their baby's birth. Parents were given a brief explanation of genes and how they can affect health and medical care, and then were asked what they thought about genomic testing of newborns.
Nearly 83 percent of the parents said they were either extremely (18 percent), very (28 percent) or somewhat (36 percent) interested in in-depth newborn genetic testing, the study found.
"Several other studies have measured parents' interest in newborn genomic screening, but none focused on new parents in the first 48 hours," senior author Dr. Robert Green, a geneticist and researcher at Brigham and Women's Hospital and Harvard Medical School, said in a hospital news release.
"Since this is when genomic testing would be of the greatest value, it is especially important to study parents' attitudes immediately post-partum," he added.
The results were similar regardless of parents' age, gender, race, ethnicity, level of education, family history of genetic disease, or whether their newborn was their first child, the researchers said.
"Parents' strong interest in genomic screening for their newborns, as demonstrated by this study, underscores the importance of further research exploring the public health impacts of actually providing this testing," said Green, "particularly as it continues to become less expensive and more widely available."
Parents who'd had concerns about the health of their newborn were less likely to be interested in genomic testing, according to the study published Dec. 4 in the journal Genetics in Medicine.
-- Robert Preidt
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The Microbiome: A New Frontier in Human Health
Traditionally the medical community has viewed microbes as the cause of illness and sought to eliminate them. This notion, however, is shifting as emerging research in the field of human microbiome...
By: Center for Genetic Medicine
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The Microbiome: A New Frontier in Human Health - Video
PUBLIC RELEASE DATE:
4-Dec-2014
Contact: Federico Santoni federico.santoni@unige.ch 022-379-5719 Universit de Genve @UNIGEnews
Cancers are due to genetic aberrations in certain cells that gain the ability to divide indefinitely. This proliferation of sick cells generates tumors, which gradually invade healthy tissue. Therefore, current therapies essentially seek to destroy cancer cells to stop their proliferation. Through high-throughput genetic sequencing of glioblastoma cells, one of the most deadly brain tumors, a team of geneticists from the University of Geneva's (UNIGE) Faculty of Medicine discovered that some of these mutations are caused by supplemental extrachromosomal DNA fragments, called double minutes, which enable cancer cells to better adapt to their environment and therefore better resist to treatments meant to destroy them. Read more in Nature Communications.
Although scientists have known for about twenty years about double minutes, little chromosomal fragments which sometimes appear during cellular division, they have just started to understand their exact function. Due to replication errors, these mini-chromosomes lack centromere, which allows them to replicate extremely rapidly and autonomously. Scientists therefore suspect that they play a role in the development of cancers, diseases that are caused by mutations in genes that control cellular metabolism and development.
Professor Stylianos Antonarakis and his team in the Genetic Medicine and Development Department of UNIGE's Faculty of Medicine, in collaboration with the Geneva University Hospitals' (HUG) Centre of Oncology, identified double minutes in glioblastoma cells with specific oncogenes. To this end, the scientists used advanced methods of bioinformatics to perform high-throughput genetic sequencing. The researchers then noticed that one of the main genetic mutations responsible for the anarchic development of cancer cells was not found on actual chromosomes, but only on these double minutes, which, given their very fast proliferation, multiplied the impact of this mutation. The researchers had therefore identified an oncogene whose malignancy was amplified by the number of its copies present on each double minute, but which was not present on the chromosomes themselves.
An Intriguing Adaptability in DNA
The Geneva team also discovered that cells can modulate the number of double minutes according to their environment, and especially in response to chemotherapy. To counter the aggression caused by these treatments and ensure its survival, the cell reduces its number of double minutes until they disappear completely. It is thus freed from the oncogenetic mutation that was present in these DNA fragments. But glioblastoma, like most cancers, depends on a combination of several genes. The tumor therefore begins to exploit a new gene in order to keep growing. Paradoxically, the cell can return to its initial chromosomal state with regards to that specific oncogene, but other oncogenic genes are then activated in the still living cell. The double minutes therefore act as adjustment variables in cancer cells and limit the effects of therapies, explains Sergei Nikolaev, joint lead author of the study.
These mini-chromosomes amplify the harmful effects of oncogenes and give a selective advantage to sick cells compared with healthy cells, as the tumor grows. In fact, their presence has been detected in most very aggressive cancers. We must absolutely continue our research in order to better understand this phenomenon of DNA adaptation, emphasizes Federico Santoni, joint lead author of this study. This will allow us to better measure its implications, and perhaps to find more effective therapeutic strategies against the deadliest cancers, he concludes.
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Most patients with triple-negative breast cancer should undergo genetic testing for mutations in known breast cancer predisposition genes, including BRCA1 and BRCA2, a Mayo Clinic-led study has found. The findings come from the largest analysis to date of genetic mutations in this aggressive form of breast cancer. The results of the research appear in the Journal of Clinical Oncology.
"Clinicians need to think hard about screening all their triple-negative patients for mutations because there is a lot of value in learning that information, both in terms of the risk of recurrence to the individual and the risk to family members. In addition, there may be very specific therapeutic benefits of knowing if you have a mutation in a particular gene," says Fergus Couch, Ph.D., professor of laboratory medicine and pathology at Mayo Clinic and lead author of the study.
The study found that almost 15 percent of triple-negative breast cancer patients had deleterious (harmful) mutations in predisposition genes. The vast majority of these mutations appeared in genes involved in the repair of DNA damage, suggesting that the origins of triple-negative breast cancer may be different from other forms of the disease. The study also provides evidence in support of the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients.
Triple-negative breast cancer is a specific subset of breast cancer that makes up about 12 to 15 percent of all cases. The disease is difficult to treat because the tumors are missing the estrogen, progesterone and HER-2 receptors that are the target of the most common and most effective forms of therapy. However, recent studies have suggested that triple-negative breast cancer patients might harbor genetic mutations that make them more likely to respond to alternative treatments like cisplatin, a chemotherapy agent, or PARP inhibitors, anti-cancer agents that inhibit the poly (ADP-ribose) polymerase (PARP) family of enzymes.
Dr. Couch and his colleagues decided to assess the frequency of mutations in predisposition genes in patients with triple-negative breast cancer to further delineate the role of genetic screening for individuals with the disease. The researchers sequenced DNA from 1,824 triple-negative breast cancer cases seen at 12 oncology clinics in the U.S. and Europe, as part of the Triple-Negative Breast Cancer Consortium.
They found deleterious mutations in almost 15 percent of triple-negative breast cancer patients. Of these, 11 percent had mutations in the BRCA1 and BRCA2 genes and the rest had mutations in 15 other predisposition genes, including the DNA repair genes PALB2, BARD1, and RAD51C. No mutations were found in predisposition genes involved in other processes like the cell cycle.
"Triple-negative breast cancers are different from all the other breast cancers," says Dr. Couch. "Other studies have suggested that this form of the disease might be associated with some defect in DNA repair, and our study verifies that. Our findings generate a whole new set of hypotheses about how triple-negative breast cancer might be arising, which could give us better ideas for prevention or new therapies for this disease."
The study also found that individuals with mutations in predisposition genes were diagnosed at an earlier age and had higher-grade tumors than those without mutations. The researchers used their dataset to assess whether the current screening guidelines would identify all the triple-negative individuals with mutations in the two most common predisposition genes, BRCA1 and BRCA2.
They found that the NCCN guidelines, which recommend screening when there is a family history of cancer or a diagnosis under age 60, missed only 1 percent of patients carrying mutations. In contrast, the UK's National Institute for Clinical Excellence (NICE) guidelines, which use the probability of actually finding a mutation to determine who should be tested, missed 24 percent of mutation carriers.
"Our results confirm that the NCCN guidelines are good, and provide evidence to support what they have recommended," says Dr. Couch. "But we think the NICE guidelines could be expanded to include more of the triple-negative breast cancer patients with mutations."
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Triple-negative breast cancer patients should undergo genetic screening
PUBLIC RELEASE DATE:
1-Dec-2014
Contact: Emmanouil Dermitzakis emmanouil.dermitzakis@unige.ch 41-223-795-483 Universit de Genve @UNIGEnews
Personalized medicine uses methods of molecular analysis, especially genetic sequencing and transcription, in order to simultaneously identify genetic mutations to evaluate each individual's risk of contracting a given disease. It seems that there is more than a single mechanism at hand, as proven by the work of a team of geneticists at the University of Geneva's (UNIGE) Faculty of Medicine, and the Swiss Institute for Bioinformatics (SIB). They have sequenced the RNA of 400 pairs of twins; with this information, they can quantify the roles of both genetic and environmental context on the expression of genes. They concluded that establishing the list of mutations present in a person's genome is not sufficient to predict that person's future health. The study can be found in the latest online edition of Nature Genetics.
What influence does the environment have on genes activity? How do certain types of mutations interact with one another in a single individual? These are the complex interactions that Emmanouil Dermitzakis, Louis-Jeantet Professor in the Department of Genetic Medicine and Development at the UNIGE's Faculty of Medicine, and his team have sought to understand, working together with scientists from Kings College London and the Wellcome Trust Sanger Institute.
Although we know that carriers of the same mutation do not necessarily both develop the same disease, how much of this discrepancy is due to genetics and how much is environmental remains unclear. Understanding how a mutation behaves when confronted with another mutation, on the one hand, and assessing the person's environmental context, on the other, forms the basis of the complex challenge of true personalized medicine.
Twins that are similar, but not identical
In Geneva, the scientists sequenced the RNA of 400 pairs of monozygotic and dizygotic twins and combined this information with genetic variations that had already been identified in these subjects. In this large sample, they identified a significant series of mutations that controlled gene expression. The researchers discovered that the influence that purely genetic (between genes) and environmental interactions (between a gene and the environment) had on gene expression were both substantial. They conclude that genetic or environmental context contributes significantly to the way in which a person's genetic composition is expressed, as well as to their risk of developing certain diseases.
The researchers used the differences between monozygotic twins, whose genomes are identical, to identify mutations that interact with the environment. Dizygotic twins, who only share half of their genome, but who were raised in the same environment, allowed researchers to separate purely genetic effects from effects caused by the similar environmental context in which the twins were raised.
We have discovered that the genetic and environmental contexts of a mutation have a much greater influence on its expression in a given individual than we previously thought, emphasized Dr Alfonso Buil, lead author of this study. Understanding the architecture of genetic expression constitutes an essential step in understanding the genetic bases of complex diseases, he adds.
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Genes and environment: Complex interactions at the heart of personalized medicine
PUBLIC RELEASE DATE:
1-Dec-2014
Contact: David Slotnick newsmedia@mssm.edu The Mount Sinai Hospital / Mount Sinai School of Medicine @mountsinainyc
(NEW YORK - December 1, 2014) Kidneys donated by people born with a small variation in the code of a key gene may be more likely, once in the transplant recipient, to accumulate scar tissue that contributes to kidney failure, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published today in the Journal of Clinical Investigation.
If further studies prove the variation to cause fibrosis (scarring) in the kidneys of transplant recipients, researchers may be able to use it to better screen potential donors and improve transplant outcomes. Furthermore, uncovering the protein pathways that trigger kidney fibrosis may help researchers design drugs that prevent this disease process in kidney transplant recipients, and perhaps in all patients with chronic kidney disease.
"It is critically important that we identify new therapeutic targets to prevent scarring within transplanted kidneys, and our study has linked a genetic marker, and related protein pathways, to poor outcomes in kidney transplantation," said Barbara Murphy, MD, Chair, Department of Medicine, Murray M. Rosenberg Professor of Medicine (Nephrology) and Dean for Clinical Integration and Population Health at the Icahn School of Medicine at Mount Sinai. "Drug designers may soon be able to target these mechanisms."
A commonly used study type in years, the genome-wide association study (GWAS) looks at differences at many points in the genetic code to see if, across a population, any given variation in the genetic code is found more often in those with a given trait; in the case of the current study, with increased fibrosis in recipients of donated kidneys.
Even the smallest genetic variations, called single nucleotide polymorphisms (SNPs), can have a major impact on a trait by swapping just one of 3.2 billion "letters" making up the human DNA code. The current study found a statistically significant association between SNP identified as rs17319721 in the gene SHROOM3 and progressive kidney scarring (fibrosis) and function loss in a group of kidney donors, mostly of European descent. In many cases, certain SNPs will be more common in families or ethnic groups.
The kidneys filter the blood to remove extra blood sugar and waste products that trickle down the kidney tubes to become urine, while re-absorbing key nutrients. The build-up of scar tissue in these delicate structures over time interferes with proper renal function.
Chronic kidney disease already affects 10 percent of US adults and its prevalence is increasing. Along with leading to kidney failure in many cases, chronic kidney disease increases the risk of cardiovascular disease. Fibrosis in kidney tubules is a common pathogenic process for many types of chronic kidney disease, and a central part of chronic disease in donated kidneys (chronic allograft nephropathy, or CAN).
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Genetic marker may help predict success of kidney transplants
Released: 1-Dec-2014 5:00 PM EST Source Newsroom: Mayo Clinic Contact Information
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Newswise ROCHESTER, Minn. Most patients with triple-negative breast cancer should undergo genetic testing for mutations in known breast cancer predisposition genes, including BRCA1 and BRCA2, a Mayo Clinic-led study has found. The findings come from the largest analysis to date of genetic mutations in this aggressive form of breast cancer. The results of the research appear in the Journal of Clinical Oncology.
Clinicians need to think hard about screening all their triple-negative patients for mutations because there is a lot of value in learning that information, both in terms of the risk of recurrence to the individual and the risk to family members. In addition, there may be very specific therapeutic benefits of knowing if you have a mutation in a particular gene, says Fergus Couch, Ph.D., professor of laboratory medicine and pathology at Mayo Clinic and lead author of the study.
The study found that almost 15 percent of triple-negative breast cancer patients had deleterious (harmful) mutations in predisposition genes. The vast majority of these mutations appeared in genes involved in the repair of DNA damage, suggesting that the origins of triple-negative breast cancer may be different from other forms of the disease. The study also provides evidence in support of the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients.
Triple-negative breast cancer is a specific subset of breast cancer that makes up about 12 to 15 percent of all cases. The disease is difficult to treat because the tumors are missing the estrogen, progesterone and HER-2 receptors that are the target of the most common and most effective forms of therapy. However, recent studies have suggested that triple-negative breast cancer patients might harbor genetic mutations that make them more likely to respond to alternative treatments like cisplatin, a chemotherapy agent, or PARP inhibitors, anti-cancer agents that inhibit the poly (ADP-ribose) polymerase (PARP) family of enzymes.
Dr. Couch and his colleagues decided to assess the frequency of mutations in predisposition genes in patients with triple-negative breast cancer to further delineate the role of genetic screening for individuals with the disease. The researchers sequenced DNA from 1,824 triple-negative breast cancer cases seen at 12 oncology clinics in the U.S. and Europe, as part of the Triple-Negative Breast Cancer Consortium.
They found deleterious mutations in almost 15 percent of triple-negative breast cancer patients. Of these, 11 percent had mutations in the BRCA1 and BRCA2 genes and the rest had mutations in 15 other predisposition genes, including the DNA repair genes PALB2, BARD1, and RAD51C. No mutations were found in predisposition genes involved in other processes like the cell cycle.
Triple-negative breast cancers are different from all the other breast cancers, says Dr. Couch. Other studies have suggested that this form of the disease might be associated with some defect in DNA repair, and our study verifies that. Our findings generate a whole new set of hypotheses about how triple-negative breast cancer might be arising, which could give us better ideas for prevention or new therapies for this disease.
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Triple-Negative Breast Cancer Patients Should Undergo Genetic Screening: Mayo Clinic
PUBLIC RELEASE DATE:
1-Dec-2014
Contact: Renatt Brodsky renatt.brodsky@mountsinai.org The Mount Sinai Hospital / Mount Sinai School of Medicine @mountsinainyc
The most commonly used medications for osteoporosis worldwide, bisphosphonates, may also prevent certain kinds of lung, breast and colon cancers, according to two studies led by researchers at the Icahn School of Medicine at Mount Sinai and published today in the Proceedings of the National Academy of Sciences (PNAS).
Bisphosphonates had been associated by past studies with slowed tumor growth in some patients but not others, and the mechanism behind these patterns was unknown. In the studies published today, an international research team showed that bisphosphonates block the abnormal growth signals passed through the human EGF receptors (HER), including the forms of this protein family that make some tumors resistant to leading treatments. The connection between bisphosphonates and HER receptors was detected first in a genetic database analysis and confirmed in studies of human cancer cells and in mice.
"Our study reveals a newfound mechanism that may enable the use of bisphosphonates in the future treatment and prevention of the many lung, breast and colon cancers driven by the HER family of receptors," said lead study author Mone Zaidi, MD, Professor of Medicine and of Structural and Chemical Biology within the Icahn School of Medicine at Mount Sinai, Director of the Mount Sinai Bone Program and a member of the Tisch Cancer Institute at Mount Sinai. "Having already been approved by the FDA as effective at preventing bone loss, and having a long track record of safety, these drugs could be quickly applied to cancer if we can confirm in clinical trials that this drug class also reduces cancer growth in people. It would be much more efficient than starting drug design from scratch."
Of the two newly published PNAS papers, one describes the evidence that bisphosphonates block abnormal growth signals through HER family receptors, while the second examines the potential applications for this new mechanism: cancer prevention, combination with existing treatments, and use against treatment-resistant tumors.
Stop Abnormal Growth
The study results revolved around the human epidermal growth factor receptor (HER/EGFR) family, which consists of four types of transmembrane tyrosine kinase receptors: HER1, HER2, HER3, and HER4. HER family members occur on the surfaces of many cell types and regulate cell division and proliferation, processes closely linked to both normal tissue growth and the abnormal growth seen in cancer.
A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by random genetic changes (somatic mutations) that make HER family receptor tyrosine kinases more active drivers of abnormal growth. About of 30 percent of nonsmall cell cancers (NSCLCs) and 90 percent of colon cancers are driven by small genetic changes in HER1, while 25 percent of breast cancers proceed from genetic changes that result in excessive amounts of HER2.
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Widely used osteoporosis drugs may prevent breast, lung and colon cancers