Category Archives: Transhuman News

THURSDAY, June 22, 2017 (HealthDay News) -- Certain genes linked to heart disease may also improve your chances of having children, a new study suggests.

Australian researchers said the findings seem to offer a potential explanation for why evolution has allowed these genes to persist for centuries.

While lifestyle is clearly important in heart disease risk, scientists have found many genes also influence those odds.

"Genes play a very important role in coronary artery disease risk across an individual's lifetime," said study author Sean Byars, a research fellow at the University of Melbourne. In fact, it's estimated that genes account for about 50 percent of the risk.

The rest, he said, is due to other factors, including habits like smoking and eating a poor diet.

Heart disease is a major killer worldwide, and it has long plagued humanity. Scientists have found evidence of clogged arteries in Egyptian mummies, Byars and his colleagues pointed out.

The researchers said that raises a fundamental question: Why haven't the genes that promote heart disease been weeded out by natural selection?

Natural selection is the process by which organisms -- including humans -- evolve to have better survival odds.

The new study suggests one answer: Byars' team found that a few dozen genes tied to heart disease might also contribute to people's "reproductive success."

Since heart disease usually strikes later in life, after people have had their kids, it would be a reasonable trade-off for better fertility -- at least in terms of survival of the species.

The findings, published online recently in the journal PLOS Genetics, do not have any immediate implications for managing heart disease or fertility, Byars said.

"This study is more about potentially helping to provide a fundamental understanding of why [heart disease] is so prevalent in modern humans," he explained.

Byars did, however, point to a big-picture issue: The findings may sound a cautionary note about "gene-editing" -- a technology scientists are studying with the hope of correcting genetic flaws that cause disease.

"One potential concern a study like this raises," Byars said, "is that in an era of gene-editing, we need to be very careful about unintended consequences of modifying our genomes -- due to shared functions of these genes that are not always obvious."

For the study, the researchers used two large databases with a wealth of genetic information, along with data from a long-running health study of U.S. adults.

The investigators first focused on 76 genes that are linked to heart disease -- the kind caused by clogged arteries. From there, the researchers found that 40 genes were also tied to at least one aspect of reproductive "fitness."

Some were related to the number of children people had, while others were tied to a woman's age at her first and last menstrual period. There were 19 to 29 genes, the researchers said, that were tied to "traits" that can directly sway male or female fertility.

Heart disease is, of course, a complex condition that involves many different factors. Even if Mother Nature insists that humans carry heart-disease genes, there is still plenty that people can do about it, according to Dr. Robert Rosenson.

Rosenson, a cardiologist at Mount Sinai Health System in New York City, pointed to the example of familial hypercholesterolemia (FH).

FH is an inherited disorder caused by a single genetic defect, and it leads to very high "bad" cholesterol levels and a substantial risk of premature heart disease.

But even with those genetic cards stacked against them, Rosenson said, people with FH can prevent or delay heart complications -- by taking cholesterol medication, exercising regularly, not smoking and eating a healthy diet.

"Even if you have a disease-causing genetic trait, lifestyle absolutely makes a difference," Rosenson said.

Most genes tied to heart disease do not have such a dramatic effect -- a large number, he noted, have a "minor" impact on heart disease risk.

But studying the genetics of heart disease will hopefully lead to better treatments, Rosenson said.

Genes, he explained, may help explain why one person responds well to a cholesterol-lowering statin, while someone else "gains weight and develops diabetes," for example.

"Someone might develop a drug side effect simply because they've inherited a trait that interferes with a drug-elimination pathway," Rosenson said.

The hope for the future, he said, is to use genetic information to help predict which treatments will likely benefit an individual patient.

Here is the original post:
Heart Disease: A Price Humans Pay for Fertility? - Twin Falls Times-News

This allows us to illuminate dark corners of the genome like never before, Ashley said. Technology is such a powerful force in medicine. Its mind-blowing that we are able to routinely sequence patients genomes when just a few years ago this was unthinkable.

The study was conducted in collaboration with Pacific Biosciences, a biotechnology company in Menlo Park, California, that has pioneered a type of long-read sequencing. Lead authorship of the paper is shared by Jason Merker, MD, PhD, assistant professor of pathology and co-director of the Stanford Clinical Genomics Service, and Aaron Wenger, PhD, of Pacific Biosciences.

The type of long-read sequencing developed by the research teams collaborators at the company can continuously spool long threads of DNA for letter-by-letter analysis, limiting the number of cuts needed.

This is exciting, said Ashley, because instead of having 100-base-pair words, you now have 7,000- to 8,000-letter words.

Thanks to technological advances and increased efficiency, the cost of long-read sequencing has been falling dramatically. Ashley estimated the current cost of the sequencing used for this study at between $5,000 and $6,000 per genome.

Though the cost of short-read sequencing is now below $1,000, according to Ashley, parts of the genome not accessible when cutting DNA into small fragments. Throughout the genome, series of repeated letters, such as GGCGGCGGC, can stretch for hundreds of base pairs. With only 100-letter words, it is impossible to know how long these stretches are, and the length can critically determine someones predisposition to disease.

Additionally, some portions of the human genome are redundant, meaning there are multiple places a 100-base pair segment could potentially fit in, said Ashley. This makes it impossible to know where to place those segments when reassembling the genome. With longer words, that happens much less often.

Given these issues, 5 percent of the genome cannot be uniquely mapped, the researchers wrote. And any deletions or insertions longer than about 50 letters are too long to detect.

For patients with undiagnosed conditions, short-read sequencing can help doctors provide a diagnosis in about one-third of cases, said Ashley. But Ramons case was not one of those.

The technique initially used to analyze Ramons genes failed to identify a mutation in the gene responsible for Carney complex, though Ashley said co-author Tam Sneddon, DPhil, a clinical data scientist at Stanford Health Care who browsed through the database of Ramons sequenced genome by hand, did notice something looked wrong. Ultimately, the long-read sequencing of Ramons genome identified a deletion of about 2,200 base-pairs and confirmed that a diagnosis of Carney complex was indeed correct.

This work is an example of Stanford Medicines focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

Carney complex arises from mutations in the PRKAR1A gene, and is characterized by increased risk for several tumor types, particularly in the heart and hormone-producing glands, such as ovaries, testes, adrenal glands, pituitary gland and thyroid. According to the National Institutes of Health, fewer than 750 individuals with this condition have been identified.

The most common symptom is benign heart tumors, or myxomas. Open heart surgery is required to remove cardiac myxomas; by the time Ramon was 18 years old, hed had three such surgeries. He is under consideration for a heart transplant, and having the correct diagnosis for his condition was important for the transplant team. Beyond the typical screening for a transplant, Ashley said the team needed to ensure there werent other health issues that could be exacerbated by immune suppressants, which heart transplant patients must take to avoid rejection of the donated organ.

Though it helps his medical team to have a confirmed diagnosis of Carney complex, Ramon has found it disheartening to face the fact that he cannot escape his condition. I was pretty sad, he said. It took me a while to come to terms with the fact that Ill have this until the day I die.

He tries not to dwell on it, though. Live one day at a time, he said. The bad days are temporary storms, and theyll pass.

His story is quite incredible, said Ashley, who said it was a privilege to be working on Ramons team. To have such a burden on such young shoulders, and to decide whether or not he wants a transplant, requires incredible courage.

Because he couldnt wait any longer for a transplant, Ramon recently underwent his fourth surgery to remove three tumors in his heart. Joseph Woo, MD, professor and chair of cardiothoracic surgery, performed the operation at Stanford Hospital. It is exceedingly rare to have tumors in the heart, said Ashley. It was a particularly heroic operation. Though Ramon is still under consideration for a transplant, the need is less urgent now.

Im in good hands, Ramon said of the Stanford team. Im glad to be here.

Ashley said he and many other doctors believe that long-read technology is part of the future of genomics.

Now we get to see how to do it better, said Ashley. If we can get the cost of long-read sequencing down to where its accessible for everyone, I think it will be very useful.

Other Stanford co-authors of the study are genetic counselor Megan Grove; former graduate student Zach Zappala, PhD; postdoctoral scholar Laure Fresard, PhD; senior research engineer Daryl Waggott, MSc; Sowmi Utiramerur, MS, director of bioinformatics for Stanfords Clinical Genomics Service; research assistant Yanli Hou, PhD; research scientist Kevin Smith, PhD; Stephen Montgomery, PhD, assistant professor of pathology and of genetics; Matthew Wheeler, MD, PhD, clinical assistant professor of cardiovascular medicine; Jillian Buchan, PhD, clinical assistant professor of pathology; and James Ford, MD, professor of medicine and of genetics.

Ashley is a member of Stanford Bio-X, the Stanford Cardiovascular Institute and the Stanford Child Health Research Institute. He is also the founding director of the Stanford Center for Inherited Cardiovascular Disease, the co-director of the Stanford Clinical Genomics Service and the steering committee co-chair for the National Institutes of Health Undiagnosed Diseases Network.

Pacific Biosciences paid for the sequencing.

Stanfords Department of Pathology and the Stanford Cancer Institute also supported the work.

Originally posted here:
Researchers use long-read genome sequencing for first time in a ... - Stanford Medical Center Report

Meeting a young patient with Zellweger syndrome, a rare, life-threatening genetic disease, started a scientific investigation that culminated with an unexpected discovery. The condition, also known as peroxisomal biogenesis disorder, had been linked only to lipid or fat metabolism. Now, as a team of scientists from several institutions, including Baylor College of Medicine, reveals in PLoS Genetics, the condition also affects sugar metabolism. The discovery of this connection in animal models can potentially lead to treatments that might improve the condition.

Meeting this patient at Texas Childrens Hospital inspired me to begin a research investigation to learn more about this disorder, said first and corresponding author Dr. Michael Wangler, assistant professor of molecular and human genetics at Baylor College of Medicine. The family of the patient found out about this research and offered to help. They started Zellfest, a fundraising event in San Antonio, Texas, that has partially supported our investigation. This led us to study this disorder in the fruit fly model in collaboration with the research team led by Dr. Hugo Bellen, professor of molecular and human genetics and investigator at the Howard Hughes Medical Institute at Baylor College of Medicine.

Peroxisomal biogenesis disorder results from defects in the genes that form the peroxisomes, essential micro-machines inside the cell that are involved in breaking down and producing certain lipids. When peroxisomes do not form, people develop a wide range of conditions that may include poor muscle tone, seizures, hearing and vision loss, poor feeding, skeletal abnormalities, as well as life-threatening problems in organs such as the liver, heart and kidney. There is no cure or treatment, other than palliative care.

Its been well established that several lipid pathways are altered in this disease; these are known peroxisomal functions, but there has been very little focus on other parts of metabolism. Everybody was thinking this was mainly a lipid disorder, Wangler said.

The researchers genetically engineered the laboratory fly, Drosophila, to lack two of the genes that are needed to make peroxisomes, PEX2 and PEX16, and then analyzed the flies metabolism.

We began a collaboration with Dr. James McNew, professor in biosciences at Rice University, who had started looking at flies using a metabolomics approach, Wangler said. Metabolomics is like taking a snapshot of all the metabolism of an organism by measuring hundreds of small molecules all at once, rather than focusing on one molecule at a time. We analyzed lipids, small carbohydrates, amino acids, cholesterol and small lipids. This approach gave us a general view of the metabolism of the organism.

The scientists found that the flies lacking the peroxisome genes had many of the problems observed in patients. The scientists learned, for instance, that these flies had short lives and locomotor problems. Their thorough analysis suggests that flies without PEX genes represent an animal model in which to further investigate the human condition.

In addition, we were surprised to discover that these flies were very sensitive to low-sugar diet, Wangler said. They cannot tolerate a low-sugar diet as well as normal flies; without sugar, flies without peroxisomes appear to be starving.

The researchers also applied a metabolomics approach to mice genetically engineered to lack a mouse PEX gene. As they had found in the flies, mice without peroxisomes also had alterations in the metabolism of sugars.

Our understanding is that the enzymes that break down sugars are not directly connected to peroxisomes, Wangler said. We are continuing our investigations and hope they will lead us to better understand how sugar metabolism is linked to peroxisomal biogenesis disorders.

Peroxisomes also play a role in common diseases such as Alzheimers and cancer, Wangler said. Studying this rare disease can help us understand peroxisomes better, and, in turn, that knowledge will help clarify the role of peroxisomes in Alzheimers and other disorders. Rare diseases can help understand issues that also contribute to more common diseases.

Other authors that contributed to this work include Yu-Hsin Chao, Vafa Bayat, Nikolaos Giagtzoglou, Abhijit Babaji Shinde, Nagireddy Putluri, Cristian Coarfa, Taraka Donti, Brett H. Graham, Joseph E. Faust, Ann Moser, Marco Sardiello and Myriam Baes. The authors are affiliated with one of more of the following institutions: Baylor College of Medicine, Texas Childrens Hospital, KU Leuven, Rice University and the Howard Hughes Medical Institute.

This work was supported by the Clayton Murphy Peroxisomal Disorders Research Fund at Baylor College of Medicine, National Institutes of Health K08 (NS076547) award to Michael Wangler, a grant by the Simmons Family Foundation to foster collaborative efforts between Rice University and Texas Childrens Hospital, awarded to Michael Wangler, Hugo Bellen and James McNew, as well as the support of Hugo Bellen, a Howard Hughes Medical Investigator.

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Patient-inspired research uncovers new link to rare disorder - Baylor College of Medicine News (press release)

THURSDAY, June 22, 2017 (HealthDay News) -- Simple changes to your lifestyle might delay the start of dementia or slow its progression, a new report suggests.

Some scientific evidence indicates that keeping your mind active through "cognitive training," controlling your blood pressure and exercising more may pay dividends in terms of brain health, researchers determined.

Although not yet proven to thwart the cognitive decline that accompanies aging or dementia, the public should have access to this information, said Alan Leshner. He led the committee at the National Academies of Sciences, Engineering and Medicine that compiled the report.

"There are a few domains where the evidence that does exist suggests they might have an effect," said Leshner.

"At least two of those, we know, are good for a whole lot of other things that people do or that they could suffer from. That's controlling your blood pressure if you have hypertension and engaging in physical exercise," said Leshner, CEO emeritus of the American Association for the Advancement of Science.

Leshner's group was asked by the U.S. National Institute on Aging to research measures that might delay mild mental decline or Alzheimer's-like dementia.

Specialists welcomed the findings, which the researchers deemed encouraging even if not definitive.

"It's high time that people are given information about things they can do today to reduce their risk of cognitive decline and possibly dementia," said Keith Fargo, director of scientific programs and outreach at the Alzheimer's Association.

"Everyone is worried" about their mental functioning, he said. "But you shouldn't feel helpless. You should take control of your brain health," he added.

According to the report, which was released June 22, three promising areas for future research include:

He said the committee did not try to pinpoint which mental activities might be best; how low blood pressure should go; or how much exercise one needs to get the most benefit.

These are areas that need more research. Randomized trials are the "gold standard" of research and are the only ones that can prove or disprove a benefit from an intervention, he said.

One dementia specialist said some biological evidence supports the benefit of exercise, but in the final analysis, genetics might be the biggest determinant of whether you develop dementia.

"There is good evidence that physical exercise delays onset or slows progression [of dementia], perhaps because exercise stimulates release of nerve cell survival substances," said Dr. Sam Gandy. He directs the Center for Cognitive Health at Mount Sinai Hospital in New York City.

There is also good evidence that in people who carry the APOE4 gene mutation, which predisposes them to Alzheimer's, exercise can erase amyloid from their brains. Amyloid plaque is a hallmark of Alzheimer's disease, he said.

However, it's also possible that "genetic loading" for dementia is so strong in some people that diet and lifestyle will never be enough to prevent mental decline, he said.

Even without scientific backup for these lifestyle improvements, Leshner said they're worthwhile in their own right to improve other aspects of your health, such as preventing heart disease and strokes and improving the quality of your life.

"They're good for a whole bunch of other things," Leshner said.

Excerpt from:
Lifestyle Changes Might Prevent or Slow Dementia - Twin Falls Times-News

When the race to sequence the human genome was reaching a fever pitch in the early 2000s, when I was in high school, I couldnt help but wonder, What comes next? Once we had full access to our genetic blueprint, what more was there to do?

As it turned out, the understanding of human genetics is much more complicated than Id imagined as a teen. And understanding how human health hinges upon the strings of molecular letters within our DNA isnt always easy, either.

Researchers at Stanford, in collaboration with the biotechnology company Pacific Biosciences, are working to push past some of the limitations of current sequencing technology. Their goal is to make full-genome sequencing accessible for clinical use. The team has used a new sequencing technology called long-read sequencing in a patient for the first time. I described their work in a press release:

Current sequencing technologies cut DNA into words that are about 100 base-pairs, or letters, long, according to the studys senior author, Euan Ashley, DPhil, FRCP, professor of cardiovascular medicine, of genetics and of biomedical data science at Stanford. Long-read sequencing, by comparison, cuts DNA into words that are thousands of letters long.

This allows us to illuminate dark corners of the genome like never before, Ashley said. Technology is such a powerful force in medicine, he added. Its mind-blowing that we are able to routinely sequence patients genomes when just a few years ago this was unthinkable.

In this study, which appears in Genetics in Medicine, the team used long-read sequencing to examinea part of Ricky Ramons genes that hadnt been successfully sequenced with current technology. Ramon, who is 26, has had benign tumors throughout his body since he was about 7 years old, but doctors couldnt pinpoint a diagnosis. Especially problematic were the tumors in Ramons heart, which required open-heart surgery to remove.

The team thought Ramons symptoms were indicative of Carney complex, an extremely rare genetic condition, but the sequencing method they used initially did not identify any changes to the gene responsible.

Carney complex arises from mutations in the PRKAR1A gene, and is characterized by increased risk for several tumor types, particularly in the heart and hormone-producing glands, such as ovaries, testes, adrenal glands, pituitary gland and thyroid. According to the National Institutes of Health, fewer than 750 individuals with this condition have been identified.

The most common symptom is benign heart tumors, or myxomas. Open heart surgery is required to remove cardiac myxomas; by the time Ramon was 18 years old, hed had three such surgeries.

The long-read sequencing gave Ramons team of doctors at Stanford a confirmed diagnosis of Carney complex, which allows them to make better-informed recommendations about his treatment.

Though having confirmation of a permanent genetic condition can be disheartening at times, Ramon told me: Im in good hands Im glad to be here.

Previously: Clinical guidance on genetic testing: A Q&A, New tool to ID disease-causing genetic changes developed at Stanfordand Mystery solved: Researchers use genetic tools to diagnose young girls rare heart condition Photo by MIKI Yoshihito

Original post:
New genome sequencing method helps diagnose a rare genetic condition - Scope (blog)