Monthly Archives: June 2017

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