When most of us come down with a bacterial infection, we generally bounce back with appropriate treatment in a matter of days. But that’s often not the case for people who suffer from common variable immunodeficiency (CVID), a group of rare disorders that increase the risk of life-threatening bacterial infections of the lungs, sinuses, and intestines. CVID symptoms typically arise in adulthood and often take many years to diagnose and treat, in part because its exact molecular causes are unknown in most individuals.
Now, by combining the latest in genomic technology with some good, old-fashioned medical detective work, NIH-funded researchers have pinpointed the genetic mutation responsible for an inherited subtype of CVID characterized by the loss of immune cells essential to the normal production of antibodies . This discovery, reported recently in The New England Journal of Medicine, makes it possible at long last to provide a definitive diagnosis for people with this CVID subtype, paving the way for them to receive more precise medical treatment and care. More broadly, the new study demonstrates the power of precision medicine approaches to help the estimated 25 to 30 million Americans who live with rare diseases .
Tags: B cells, common variable immunodeficiency, CVID, exome, gamma globulin, genetic counseling, genomics, IKAROS, IKAROS deficiency, immunology, passive immunity, precision medicine, primary immune deficiency, rare disease, transcription factor
An impressive number of fundamental advances in our understanding of cancer have occurred over the past several decades. One of the most profound is the realization that cancer is a disease of the genome, driven by a wide array of changes in DNA—some in the germline and affecting all cells of the body, but most occurring in individual cells during life (so-called “somatic mutations”). As the technology for sequencing cancer genomes has advanced, we are learning that virtually all cancers carry a unique set of mutations. Most are DNA copying errors of no significance (we call those “passengers”), but a few of them occur in genes that regulate cell growth and contribute causatively to the cancer (we call those “drivers”). We are now learning that it may be far more important for treating cancer to figure out what driver mutations are present in a patient’s tumor than to identify in which organ it arose. And, as a new study shows, this approach even appears to have potential to help cancer’s littlest victims.
Using genomic technology to analyze both tumor and blood samples from a large number of children who’d been newly diagnosed with cancer, an NIH-funded research team uncovered genetic clues with the potential to refine diagnosis, identify inherited cancer susceptibility, or guide treatment for nearly 40 percent of the children . The potential driver mutations spanned a broad spectrum of genes previously implicated not only in pediatric cancers, but also in adult cancers. While much more work remains to determine how genomic analyses can be used to devise precise, new strategies for treating kids with cancer, the study provides an excellent example of the kind of research that NIH hopes to accelerate under the nation’s new cancer “moonshot,” a research initiative recently announced by the President and being led by the Vice President.
Tags: BASIC3 Study, Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care, cancer, cancer diagnostics, cancer susceptibility, childhood cancer, deep sequencing, driver mutations, exome, exome sequencing, genes, genetic information, genetic testing, genomic analysis, genomics, germline mutations, molecular tumor profiles, National Cancer Moonshot, oncology, pediatric cancer, precision medicine, precision oncology, somatic mutations, tumor molecular profiling, whole-exome sequencing
Just this year, we’ve reached the point where we can sequence an entire human genome for less than $1,000. That’s great news—and rather astounding, since the first human genome sequence (finished in 2003) cost an estimated $400,000,000! Does that mean we’ll be able to use each person’s unique genetic blueprint to guide his or her health care from cradle to grave? Maybe eventually, but it’s not quite as simple as it sounds.
Before we can use your genome to develop more personalized strategies for detecting, treating, and preventing disease, we need to be able to interpret the many variations that make your genome distinct from everybody else’s. While most of these variations are neither bad nor good, some raise the risk of particular diseases, and others serve to lower the risk. How do we figure out which is which?
Jay Shendure, an associate professor at the University of Washington in Seattle, has an audacious plan to figure this out, which is why he is among the 2013 recipients of the NIH Director’s Pioneer Award.
Posted In: Science
Tags: breast cancer, CADD, Combined Annotation-Dependent Depletion, cystic fibrosis, Daniela Witten, DNA, ENCODE, epigenomics, exome, genome sequencing, human genome, Jay Shendure, multiplex approaches, NIH Early Independence Award, NIH Pioneer Award, ovarian cancer, point mutation, precision medicine, protein, variants