Heidi Rehm, PhD
When a patient gets their genome sequenced it may be for a variety of different reasons. That individual may have some sort of disease that's suspected to be inherited; so they may be looking for a genetic cause of that disease. Other individuals may get their genome sequenced because they're concerned for risk of disease. So they may want to know if they might have a child with a disorder, or if they may develop a later onset disease such as breast cancer, or have a hereditary disorder, like hypertrophic cardiomyopathy. And some individuals may just want to understand their ancestry. So there's a lot of different information in the genome that patients can learn about themselves.
When we look at a person's genome, we either may look at specific regions that are related to the disease or we may scan through the genome trying to find variants that other people have said cause disease and then we find those same variants. Then, we review the evidence and decide if we believe the genetic variants actually would cause disease. So there's a lot of work that goes into looking at a person's genome and trying to determine if we found a cause for their disease or if they're at risk for a certain disorder.
In about one to two percent of individuals that we sequence we find genetic information that puts them at very high risk for disease and that information is actionable. That’s really the minimum level, just looking only at a small subset of genes. If we begin to expand sequencing to many other genes we find information that gives risk for disease in about 15 to 20 percent of the population.
However, one of the challenges that we have is that only patients with existing disease have largely been studied. When we sequence a healthy individual’s genome and find what we thought were disease variants and we don’t see disease in those individuals, we have trouble understanding their risk.
Because today, for instance, if we sequence an individual’s genome and find a breast cancer variant we can’t really say what their chance of developing the disease is. We can say they’re at risk because that variant has been linked to disease in patients who come in with disease; but we really can’t say is it a 10 percent chance, a 50 percent chance, a 90 percent chance, because we haven’t studied the healthy population, we’ve mostly studied the diseased population.
One of the projects that I've been working on over the past few years is called ClinGen, or the Clinical Genome Resource. This is a program that's funded by NIH and the goal of the program is to better understand human genetic variation.
In a lot of the diseases that we study today we don’t fully understand the variants that cause those diseases. So if a patient gets back a genetic report, and there's a variant that is labeled uncertain significance, that's really frustrating for the patients because they want to know is that variant causing my disease, or is it not? Our goal is to help them figure that out.
So if they share that variant and their information with our genetic databases and other patients that have the same variant or variants in the same gene also share, bringing that knowledge together can help us learn more information that might eventually allow us to interpret their variant and tell them whether it actually causes disease and what else they might expect from their condition that they haven't yet observed.
Today, we're mainly focusing on those individuals who are more likely to have a rare genetic disorder. But any individual who's had any sort of genetic testing, whether it's a whole genome sequencing test, an exome sequencing test, or maybe they've had their genotype analyzed through a service, like 23andMe, all of those individuals that have genetic information and are willing to share it can register on Genome Connect.
So for individuals who are interested in getting their genome sequenced, it can certainly be ordered as a clinical test today through a physician. Although, for a healthy individual, it's largely not going to be covered by insurance and you'd likely have to pay out of pocket. It may range from $5,000 to $8,000 for a genome, maybe a little less for an exome. However, there are also research studies that are recruiting patients where the cost of the sequencing will be covered by the study.
If you or a family member is pregnant, anticipating the birth of a child, if you have that child at either Brigham and Women's Hospital or at Boston Children's Hospital, you would likely be eligible to enroll that baby into the BabySeq study for potential exome sequencing of that baby. Also, in the future, they'll soon be opening enrollment for the Precision Medicine Initiative. That's an initiative where families or individuals from across the US will be able to sign up for that study, contribute their health data, as well as have whole genome sequenced. Useful information that's actionable for those individuals will be returned to those patients through the Precision Medicine Initiative.
Learn more about Brigham and Women's Genetics and Genomic Medicine Service.
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