Category Archives: Transhuman News

PITTSBURGH, March 25, 2015 - Fetal ultrasound exams on more than 87,000 mice that were exposed to chemicals that can induce random gene mutations enabled developmental biologists at the University of Pittsburgh School of Medicine to identify mutations associated with congenital heart disease in 61 genes, many not previously known to cause the disease. The study, published online today in Nature, indicates that the antenna-like cellular structures called cilia play a critical role in the development of these heart defects.

The findings are the culmination of an effort to find the genetic determinants of structural heart disease in the "Bench to Bassinet" program, launched six years ago by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, led at Pitt by principal investigator Cecilia Lo, Ph.D., professor and chair of the Department of Developmental Biology, Pitt School of Medicine.

"This project has given us new insights into the biological pathways involved in development of the heart," Dr. Lo said. "The genes and pathways identified in our study will have clinical importance for interrogating the genetic causes of congenital heart disease in patients."

For the study, Dr. Lo's team mated mice exposed to chemicals that could create random genetic mutations, resulting in 87,355 pregnancies. They scanned each fetus using noninvasive ultrasound and recovered over 3,000 independent cases of congenital heart defects, all incompatible with life. They sequenced the genes of mutant animals and compared them to those of unaffected offspring to identify 91 recessive mutations in 61 genes.

"We were surprised to learn many of these genes were related to the cilia, or cilia-transduced cell signaling," Dr. Lo said. "These findings suggest cilia play a central role in the regulation of heart development, including patterning left-right asymmetry in the cardiovascular system critical for efficient oxygenation of blood."

She added that pathways recovered in the mouse study show overlap with those associated with de novo, or spontaneous, mutations identified in congenital heart disease patients. Co-investigators of the project include other researchers from the University of Pittsburgh; the University of Massachusetts Medical School; the Jackson Laboratory; and Children's National Medical Center.

###

The project was funded NHLBI grants HL098180 and HL098188; National Institute of Mental Health grant MH094564; National Human Genome Research Institute grant HG000330; and the University of Pittsburgh School of Medicine.

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

See the article here:
Pitt team identifies mutations associated with development of congenital heart disease

Angelina Jolie told the story yesterday of her decision to have her ovaries and fallopian tubes surgically removed to reduce the risk of ovarian cancer due to the faulty BRCA1 gene she was born with. This follows a similar decision to undergo a double mastectomy in 2013 to reduce the even higher risk of breast cancer the mutant BRCA1 gene bestows.

As a human being, its hard not to feel enormous sympathy with her for facing such a decision a thoroughly 21stCentury decision that no-one ever had to face until the advent of molecular medicine. For centuries humanity has had to face the many adversities of life head on, but for the most part without much forewarning and even less hope of intervention.

The knowledge that certain mutations in this BRCA1 gene confer such high risks of cancer (as much as 87% chance over a lifetime for breast cancer and 50% for ovarian cancer) has the potential to be empowering or frightening (and perhaps both at the same time) in equal measure.

The interventions are hugely invasive. The surgeries themselves are major, and come with short-term risks. The hormonal imbalances that will result can change not only health but also the person. But perhaps hardest of all to quantify is the psychological and emotional impact.

In addition to sympathy for having to face such a decision, Ms Jolie also deserves admiration for her self-awareness and the clarity of her thinking that has allowed her to make such a clear choice the right choice uniquely for her. Not everyone is blessed with such gifts.

That matters because we all of us are going to face these kind of decisions much more frequently in the future.

We hear from all sides about the benefits of personalized medicine the product of refined molecular diagnostics that offer a glimpse into the future health of the individual. But Ms Jolies experience of personalized medicine highlights some of the challenges that also remain.

The biggest hurdle seems to be one of education. The default state of humans is to be pretty bad at understanding risks and the output of all precision medicine algorithms is precisely that: an estimate of individual risk. While science can make the estimate more accurate, what it cannot provide is the calibration of what that risk estimate means to the individual. A 50% risk of ovarian cancer over a lifetime sounds, on the face of it, like a death sentence. But it needs some context. First and most importantly we have to remember we are all born with a death sentence. The only questions are when and how. Something like 33% of everyone alive today will suffer cancer in their lifetime.

Of course, BRCA1 mutations carry a material risk of an early death and no doubt that influenced Ms Jolies decision (as it would likely have done for most of us). But the important point is that properly understanding the implications of the genetic diagnosis is a complex education process. It cannot be nicely packaged up into a single number or a simple decision.

And BRCA1 carries one of the larger risks associated with any single genetic marker. As molecular diagnostics are refined (as they are being at an impressive rate), that picture will become more complex still and the decisions facing the patient ever more challenging.

Visit link:
What Angelina Jolie's Very Personal Medicine Tells Us About Personalized Medicine