Over the past decade, mutations to more than 60 different genes have been linked with autism spectrum disorder (ASD), including de novo mutations, which occur spontaneously and aren’t inherited. But much of autism still remains unexplained.
A new study of nearly 6,000 families implicates a hard-to-find category of de novo mutations: those that occur after conception, and therefore affect only a subset of cells. Findings were published today in Nature Neuroscience. …
How did our distinctive brains evolve? What genetic changes, coupled with natural selection, gave us language? What allowed modern humans to form complex societies, pursue science, create art?
While we have some understanding of the genes that differentiate us from other primates, that knowledge cannot fully explain human brain evolution. But with a $10 million grant to some of Boston’s most highly evolved minds in genetics, genomics, neuroscience and human evolution, some answers may emerge in the coming years.
The Seattle-based Paul G. Allen Frontiers Group today announced the creation of an Allen Discovery Center for Human Brain Evolution at Boston Children’s Hospital and Harvard Medical School. It will be led by Christopher A. Walsh, MD, PhD, chief of the Division of Genetics and Genomics at Boston Children’s and a Howard Hughes Medical Institute investigator.
“To understand when and how our modern brains evolved, we need to take a multi-pronged approach that will reflect how evolution works in nature, and identifies how experience and environment affect the genes that gave rise to modern human behavior,” Walsh says. …
Genome-wide association studies are huge undertakings that compare the genomes of large populations. They can turn up thousands to tens of thousands of genetic variants associated with disease. But which GWAS variants really matter?
That question becomes exponentially harder when the variants lie in the vast stretches of DNA that don’t encode proteins, but instead have regulatory functions.
Reporting in Cell, Sankaran’s team and two other groups at the Broad Institute describe a new tool that can looks at hundreds of thousands of genetic elements at once to pinpoint variants that truly affect gene expression or function. Called the massively parallel reporter assay (MPRA), it could help reveal subtle genetic influences on diseases and traits.
In Sankaran’s case, the MPRA is helping him understand how common variants contribute to blood disorders in children. “Most of the common variation is just tuning genetic function,” he says. “Just slightly, not turning it on or off, but actually just tuning it like a dimmer switch.”
President Obama’s Precision Medicine Initiative, first laid out in his 2015 State of Union Address, aims to develop individualized care that empowers patients and takes into account genetic, environmental and lifestyle differences. Obama is asking Congress for $309 million for the initiative next year.
One big component is the Department of Veteran Affairs’ Million Veteran Program, which has signed up more than 450,000 veterans to date and is now open to active-duty military personnel. Another is NIH support for cancer trials that match treatments with patients’ genomic profiles.
As Might detailed today at a White House summit on the Precision Medicine Initiative, he now has worms at the University of Utah modeling his son’s disease, whose symptoms include seizures, extreme developmental delay and an inability to make tears. He also has a molecular target and a list of 70 compounds that hit it, including 14 that are already approved by the FDA.
Can Might’s vision be scaled and made part of routine medical care, keeping the patient front and center? …
About 1 in 5 cases of the kidney-destroying condition nephrotic syndrome don’t respond to steroid treatment. They are a leading cause of end-stage kidney failure in children and young adults, who are quickly forced to go on dialysis or wait for a kidney transplant.
Thanks in large part to the lab of Friedhelm Hildebrandt, MD, chief of the Division of Nephrology at Boston Children’s Hospital, more is becoming known about this severe condition. Mutations in more than 30 genes have been implicated, all causing dysfunction of glomeruli, the kidney’s filtering units, specifically in cells known as podocytes. Test panels are now clinically available. Yet, in 70 percent of patients, the causative gene is still unknown.
A new study by Hildebrandt and colleagues in this week’s Nature Genetics pinpoints three new, completely unexpected genes, revealing the power of whole-genome sequencing and potentially opening a new treatment route for at least some steroid-resistant cases. …
Neurons are more like snowflakes–no two alike–than anyone realized.
Walt Whitman’s famous line, “I am large, I contain multitudes,” has gained a new level of biological relevance in neuroscience.
As we grow, our brain cells develop different genomes from one another, according to new research from Harvard Medical School and Boston Children’s Hospital. The study, published last week in Science, provides the most definitive evidence yet that somatic (post-conception) mutations exist in significant numbers in the brains of healthy people—about 1,500 in each of the neurons they sampled.
The finding confirms previous suspicions and lays the foundation for exploring the role of these non-inherited mutations in human development and disease. Already, the researchers have found evidence that the mutations occur more often in the genes a neuron uses most. And they been able to trace brain-cell lineages based on mutation patterns.
“This work is a proof of principle that if we had unlimited resources, we could actually decode the whole pattern of development of the human brain,” says co-senior investigator Christopher Walsh, MD, PhD, the HMS Bullard Professor of Pediatrics and Neurology and chief of the Division of Genetics and Genomics at Boston Children’s. “These mutations are durable memory for where a cell came from and what it has been up to. I believe this method will also tell us a lot about healthy and unhealthy aging as well as what makes our brains different from those of other animals.” …
In the U.S. alone, an estimated 30 million Americans suffer from a rare disorder. Many of them never receive a diagnosis, and often find themselves on a lonely journey, going from doctor to doctor and test to test, sometimes for many years, with no explanation for their symptoms.
How many people fall in the “undiagnosed” category is unclear, but in its first six years, the NIH’s Undiagnosed Diseases Program has received more than 10,000 inquiries. Without a diagnosis, it’s often difficult to qualify for insurance coverage, receive coordinated care or even connect with a support group.
What if the work of solving these medical mysteries could be crowd-sourced? That’s the goal of CLARITY Undiagnosed, an international challenge launching today in which scientific teams can compete to provide answers for five families with undiagnosed conditions. (Deadline for applications: June 11). …
Vast chunks of our DNA—fully 98 percent of our genome—are considered “non-coding,” meaning that they’re not thought to carry instructions to make proteins. Yet we already know that this “junk DNA” isn’t completely filler. For example, some sequences are known to code for bits of RNA that act as switches, turning genes on and off.
In a report published last month in Nature Communications, they describe a variety of proteins and peptides (smaller chains of amino acids) arising from presumed non-coding DNA sequences. Since they looked in just one type of cell—neurons—these molecules may only be the tip of a large, unexplored iceberg and could change our understanding of biology and disease. …
Vector took a moment this morning at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards to catch up with the Gene Discovery Core at the Manton Center for Orphan Disease Research. Its exhibition table doesn’t have fancy mannequins or flashy screens, but this team is rocking genetics and genomics, one patient at a time.
The usual methods for finding disease-causing genes don’t work for many patients who walk in the doors of Boston Children’s, or who mail in samples from all over the world. They may be one of just a handful of patients in the world with their condition—which may not even have a name yet. …