 The Undiagnosed Diseases Network is made up of a set of clinical sites. We have seven clinical sites, including the one here at the NIH that Dr. Gall leads. There's also a coordinating center along with two sequencing cores, and we're soon planning on adding a metabolomics core as well as a model organism screening center. And all of these different sites are going to work together to be able to try and come up with diagnoses for these undiagnosed patients. In fact, the NIH portion of that is called the NIH Undiagnosed Diseases Program, and that began in 2008. And since then, we've seen a large number of patients, probably about 850 or so, had a lot more applicants for that, and have made several diagnoses. So that was five days afterwards, and since then, have there been other episodes of this occurring? The Undiagnosed Diseases Program is within the NIH confines here on the campus in Bethesda, Maryland, and it's been going on for a number of years. But the network is an expansion of that, so the UDP, which is on campus here, will be part of the entire network, one of the seven clinical sites. We have three main objectives for the UDN. The first of these is to increase the level of diagnoses for these patients that have undiagnosed conditions. The second is to facilitate more research into these diseases that the patients have. And then finally, we're really looking to help bring together the research and clinical communities in order to facilitate a more collaborative environment to help take a patient who might have an undiagnosed condition, find a variant, and then move that into research to hopefully be able to learn more about it in order to potentially help patients in the future. A patient who applies to the UDN generally has sought a diagnosis for a rare disease for many years. Sometimes it's only a year, sometimes it's 20 years or so. They've gone to many experts in many places around the country and sometimes around the world to try to determine that diagnosis. They come desperate to us, and it's our job to try to find a diagnosis for them. They in general have not just a rare disease, which by law is defined in the United States as one that affects fewer than 200,000 individuals. They generally have a very rare disease because even the classic average rare disease will be discovered through their journey prior to seeing us. They have extremely rare disorders, and some of them have new disorders that have not been discovered at all, and it's our job to try to find those as well. In the UDN, we have two sequencing cores that are going to be providing genomic sequencing to the participants in the UDN. For all of the participants and their family members, they'll be asked to consent to be able to receive sequencing, and they'll receive back a clinical report that will provide them with information about the genomic variants that are found in that particular patient and their family members. We will be asking for blood samples from the patients and their family members in order to be able to extract DNA from those samples. This is a part of the consent in order to participate in the UDN as a research study, and so the participants will be informed about the fact that we're going to ask for this blood sample and be able to ask questions about what uses their DNA is going to be put to and how the sequencing occurs in the UDN. Physicians when they try to make a diagnosis have made use of many different modalities. For example, a physical examination or x-rays or biopsies, and now we are in an age in which we can also use genomics. So it's one of the tools that we use, and we use this not only for the patient, but also incorporating the whole family's genetics into this analysis. So genomics has become one of our primary tools, and in fact we make about half of our diagnoses in the Undiagnosed Diseases Program through the use of genomics. And one other thing that I would add that's a little unique about the UDN is that we're really working with the patients as participants as part of the network. We have patient advisors that participate in our steering committee meetings, as well as moving forward we're going to have surveys to be able to ask the patients about their experience and try to learn from that and really make sure that they're engaged in the UDN and that we hear their voice for what kind of information they would like to receive back and how we can make the process better for future patients. We always have concerns about privacy, and in fact the institutional review board that approves a protocol like this has enough concerns that we have to lay out how we're going to protect the privacy and the confidentiality of our patients, their specimens, and their DNA and their information that we get. Yes, there are security measures taken, the data are filed in databases that are only open to a certain number of people with password protection, and there are different tiers of individuals who have access to that. So some data are shared in one way and some data are shared in another way, but privacy is of the utmost concern. And we lay this all out in the consent too, so that individuals who are enrolled in these protocols know the measures that we're taking to protect their privacy. If a patient wanted to apply to the undiagnosed diseases network, there's a gateway that is available on the web where they can apply to the undiagnosed disease network as a whole. They fill out some information about where they are and a little bit about their condition and the symptoms that they have right now, and then they need to provide a physician or a health care provider referral letter along with their application packet. And then those data are set to one of the seven clinical sites for an evaluation and perhaps asking for more information. By having this network, the undiagnosed diseases network, we're able to have clinical sites across the country, which will make it easier for patients to be able to access a clinical site and they'll be closer to them. Also helps with having an expanded expertise space, and we have lots of sites that are all going to be looking at these patients and being able to contribute to finding new ways to look at these diseases and coming up with new ways to help diagnose the patients. There's an added advantage too in that we're able to share data among all these sites, so seeing more individuals and then sharing not only the genomic data based on the DNA, but also the phenotypic data or the clinical manifestations. So we may be able to find two patients with the same extremely rare or new disease, and then we learn from one patient and transfer that knowledge to our care of the other patients. So that shared information is incredibly important as a goal for the network. When we find a variant and can attach that to a particular disease, then the first thing that generally happens is we find out many more individuals who have that disease due to other variants in the same gene. So that's the first thing that comes out. But the other thing that comes out is some knowledge of the function of that gene and the dysfunction of the gene in the individual. And that speaks to a particular pathway, and that pathway often has very generic application to even common disorders. So the things that we learn from rare disease and new disease patients is really applicable to some common disorders as well, and that's another goal of this program in the network to try to find out new scientific information, new cell biology, biochemistry, pathway information that we can apply to even common diseases. And it is true that genomics is currently largely the purview of geneticists and specialists in certain fields who use genetics. But our hope is that genetics and genomics will be used by the entire medical care community. And I look to the day when a family physician can obtain genomic information and look up what her or his patient's genome looks like compared to a list of, let's say, genes that are associated with human disease. And that can help her or him make a diagnosis in that individual. We're not there yet, but this type of program will really expand the databases that will serve as the foundation for that type of medical care delivery at a very baseline primary care level.