Does autism stress families’ chromosomes?

telomeres autismThe ends of our chromosomes have little caps called telomeres that keep our DNA from degrading as our cells divide. Telomere length is partly determined by genetics. However, telomeres also shorten as we age and as a result of health conditions, including stress—as in institutionalized children in Romania and women caring for children with chronic illnesses.

An intriguing new study in the July Journal of the American Academy of Child and Adolescent Psychiatry finds shortened telomeres not just in children with autism (confirming a recent study from China) but also in their infant siblings and their mothers. An effect was also seen in fathers, but it didn’t reach statistical significance.

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Gene therapy restores hearing in deaf mice

A closeup of the sensory hair bundles in the cochlea (inverted v's), each containing 50 to 100 microvilli tipped with TMC proteins. Cell bodies are below the bundles. (Gwenaelle S. Geleoc & Artur A. Indzhykulian)
The inverted V’s above are sensory hair bundles in the ear, each containing 50 to 100 microvilli tipped with TMC proteins. Gene therapy restores hearing by providing working copies of those proteins. (Gwenaelle Geleoc & Artur Indzhykulian)

More than 70 different genes are known to cause deafness when mutated. Jeffrey Holt, PhD, envisions a day when patients with hearing loss have their genome sequenced and their hearing restored by gene therapy. A proof-of-principle study published today by the journal Science Translational Medicine takes a clear step in that direction, restoring hearing in deaf mice.

“Our gene therapy protocol is not yet ready for clinical trials—we need to tweak it a bit more—but in the not-too-distant future we think it could be developed for therapeutic use in humans,” says Holt, a scientist in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and an associate professor of Otolaryngology at Harvard Medical School.

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Power to the people: Citizen science meets precision medicine for rare disease

At this recent GoldLab Symposium presentation in Colorado, parent Matt Might shows how it’s done.

People credit rapid next-generation gene sequencing for the increased pace of medical discovery. But patients and their families—especially those with rare or undiagnosed conditions—are emerging as the true engines of precision medicine. Racing against the clock to save their children, parents are building databanks, connecting scientific dots and fueling therapeutic advances that could otherwise take a decade or more to happen.

“There’s a culture shift,” said Isaac Kohane, MD, PhD, chair of Harvard Medical School’s Department of Biomedical Informatics (DBMI), which hosted a conference titled Precision Medicine 2015: Patient Driven in late June. “A culture shift where patients feel empowered morally and intellectually to lead in precision medicine research and delivery.”

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Slow and steady wins the race: Genetic research sheds light on heart muscle disease

marathon runners close up
Manipulating genetic pathways could help diseased heart muscles gain more of the slow-twitch fibers abundant in marathon runners.

Heart muscles, like skeletal muscles, are made up of two major types of muscle fibers: fast twitch and slow twitch. Fast twitch fibers move quickly but tire easily, while slow twitch fibers move slower but last longer. Both serve important functions in different circumstances. For example, marathon runners tend to have a predominance of slow twitch fibers in their skeletal muscle; the opposite is true for sprinters.

At the Boston Children’s Hospital Cardiovascular Research Center, Da-Zhi Wang, PhD, and his colleagues recently discovered a genetic pathway responsible for fine-tuning twitch speed that, when disrupted, leads to cardiomyopathy, a disease of the heart muscle.

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So, what’s your digital phenotype?

Ideally, we’re all supposed to see our doctor once a year for a checkup. It’s an opportunity to see how we’re doing from a health perspective, address any concerns or issues that we may have and catch any emerging issues before they become true problems.

But those visits are really only one-time, infrequent snapshots of health. They don’t give a full view of how we’re doing or feeling.

Now, think for a moment about how often you post something to Facebook or Twitter. Do you post anything about whether you’re feeling ill or down, or haven’t slept well? Ever share how far you ran, the route you biked or your number of steps for the day?

Every time you do, you’re creating a data point—another snapshot—about your health. Put those data points together, and what starts to emerge is a rich view of your health, much richer than one based on the records of your occasional medical visit.

As John Brownstein, PhD—director of the Computational Epidemiology Group (CEG) in Boston Children’s Hospital’s Computational Health Informatics Program and the hospital’s new Chief Innovation Officer—explains in this episode of the Harvard Medical School (HMS) Labcast (click the image above to hear it), this view has a name: your digital phenotype.

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Detecting Ebola within minutes: A treatment and containment game changer

Ebola

Tests for detecting Ebola in the blood can take anywhere from 12 hours to four days to yield results. But a recent study published in The Lancet reveals that a new point-of-care test can accurately determine results in mere minutes—another step toward potentially controlling the spread of Ebola.

Nira Pollock, MD, PhD, senior author of the paper and associate medical director of the Infectious Diseases Diagnostic Laboratory at Boston Children’s Hospital, along with researchers from Harvard Medical School and Partners In Health, showed that a commercially developed rapid diagnostic test (RDT), called the Corgenix ReEBOV Antigen Rapid Test kit, was as sensitive as a conventional laboratory-based method used for clinical testing during the recent outbreak in Sierra Leone.

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Breaking the allergic asthma cycle…by targeting nerve endings

asthma therapeuticsExisting asthma medications work by suppressing inflammatory signaling by immune cells or by dilating constricted airways. Over time, though, these drugs’ benefits can wane. New research supports a surprising new tactic for controlling asthma: targeting sensory nerve endings in the lungs with a selective drug.

Our lungs are known to contain specialized sensory neurons known as nociceptors that connect to the brainstem. Best known for causing the perception of pain, nocieptors also trigger the cough reflex in the lungs when they detect potential harms like dust particles, chemical irritants or allergens. Nociceptor nerve endings are known to be more plentiful and more readily activated in people with asthma. Now it’s also clear that they help drive allergic inflammation.

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Gene therapy to germline editing: Promises, challenges, ethics

A report this April rocked the scientific world: scientists in China reported editing the genomes of human embryos using CRISPR/Cas9 technology. It was a limited success: of 86 embryos injected with CRISPR/Cas9, only 71 survived and only 4 had their target gene successfully edited. The edits didn’t take in every cell, creating a mosaic pattern, and worse, unwanted DNA mutations were introduced.

“Their study should give pause to any practitioner who thinks the technology is ready for testing to eradicate disease genes during [in vitro fertilization],” George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, told The New York Times. “This is an unsafe procedure and should not be practiced at this time, and perhaps never.”

As Daley detailed last week in his excellent presentation at Harvard Medical School’s Talks@12 series, the report reignited an ethical debate around tampering with life that’s hummed around genetic and stem cell research for decades. What the Chinese report adds is the theoretical capability of not just changing your genetic makeup, but changing the DNA you pass on to your children.

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Gene for salivary enzyme found unrelated to obesity

(Jaimie Duplass:Shutterstock)
child eating cracker-cropped-shutterstock_169956-Jaimie Duplass

Sometimes it’s just as important to rule a gene out as the cause of a condition as it is to rule it in, especially for complex, multi-gene traits like obesity. In a report published yesterday by Nature Genetics, a gene once thought to be the single greatest genetic influence on human obesity actually has nothing to do with body weight.

The study, led by researchers at Harvard Medical School (HMS) and Boston Children’s Hospital, also provides the first effective ways to analyze complicated parts of the genome.

The gene in question, AMY1, encodes an enzyme in our saliva that helps convert starch into sugar. “There’s been some speculation that because this enzyme helps get nutrients out of our food, it could be linked to obesity,” said Christina Usher, a graduate student at HMS and first author on the paper.

What’s complicated is that people can have anywhere from 2 to 14 copies of AMY1—or more. In 2014, an unrelated international group reported in Nature Genetics that people with fewer than four copies of AMY1 had a roughly eight times greater risk for obesity than people with more than nine copies of the gene. AMY1 therefore appeared to be protective.

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Targeting inflammation in sickle cell disease with fatty acids

sickle cell disease red blood cells
(OpenStax College/Wikimedia Commons)

Painful, tissue-damaging vaso-occlusive crises (a.k.a. pain crises) are one of the key clinical concerns in sickle cell disease (SCD). The characteristic C-shaped red blood cells of SCD become jammed in capillaries, starving tissues of oxygen and triggering searing pain. Over a patient’s life, these repeated rounds of oxygen deprivation (ischemia) can take a heavy toll on multiple organs.

There’s some debate as to why these crises take place—is the sickled cell’s shape and rigidity at fault, or are the blood vessels chronically inflamed and more prone to blockage? Either way, doctors can currently do little to treat vaso-occlusive crises, and nothing to prevent them.

The inflammation view, however, is leading some researchers to ask whether omega-3 fatty acids—which can alleviate inflammation—might be part of the solution. A recent mouse study in the journal Haematologica, led by Mark Puder, MD, PhD, of Boston Children’s Vascular Biology Program, and Carlo Brugnara, MD, of the hospital’s Department of Laboratory Medicine reveals some molecular clues and suggests that human trials of omega-3s might be a good next step.

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