Rare Disease Research at Yale: Learn about our research and help us raise awareness.
Rare Disease Day (February 29) was established to raise global awareness about the 7,000 known rare diseases and the 25-30 million people who live with them.
What is a rare disease? In the United States, a disease is considered rare if it affects fewer than 200,000 people at any given time. Rare diseases are also known as “orphan diseases” because drug companies often lack interest in supporting research on drugs that would have such a small market.
If it’s “rare” why is it so important? Although the rate of each individual condition is low, the number of people actually affected by a rare disease (25-30 million) is large. Collectively, having a rare disease is not a rare occurrence, and rare diseases have a huge impact on health systems and the population.
What are some examples of rare diseases? Rare diseases include a wide range of conditions, from birth defects to autoimmune reactions, bleeding disorders to cancers, and a variety of other ailments and system dysfunctions. Some of the better known rare diseases include muscular dystrophy, narcolepsy, cystic fibrosis, and hemophilia.
What causes rare diseases? There are many different causes of rare diseases, including infection, environmental factors, and genetics. There are an estimated 7,000 different rare diseases. More than 6,000 of these are thought to be genetic and are known as “Mendelian disorders.”
Mendelian disorders are caused by changes in genes or chromosomes. An important aspect of Mendelian disorders is that they are inheritable. In some cases, the genetic change is inherited from one or more parents, and in other cases it occurs randomly in a person for the first time.
The types of genetic changes that occur can be very small, such as modifications that affect a single gene (monogenic). They can also be more complicated, affecting multiple genes (polygenic) or even large segments of chromosomes. These changes to the genetic code disrupt the normal function of proteins and other signaling molecules that are involved in important cellular and tissue-level processes in the body, ultimately leading to the disorders.
Yale Center for Genome Analysis (YCGA) The Yale Center for Genome Analysis (YCGA) provides RNA expression profiling, DNA genotyping, and high-throughput sequencing for research conducted at both Yale and other non-profit organizations. Learn more about YCGA.
Operating under YCGA is also the Yale Center for Mendelian Genomics (CMG). Yale University is home to one of four national centers created by the National Institutes of Health (NIH) to study the genetics of rare inherited diseases. Through this program, the Yale CMG receives support to perform next-generation sequencing and computational approaches to discover the genes and variants that underlie Mendelian disorders. The discovery of genes that cause Mendelian conditions will expand our understanding of how the human body works, paving the way for earlier diagnosis and, potentially, new treatments.
Yale Center for Genomic Health (YCGH) and the Generations Project Last fall, the Yale Center for Genomic Health (YCGH) launched one of the largest DNA sequencing projects in the United States. The goal is to enroll more than 100,000 volunteers who will have their DNA analyzed at a level of detail far greater than what is currently available via at-home genetic testing kits. The ultimate goal is to find out more about human health and disease. Some of these findings may provide valuable insight into specific rare diseases.
At the same time, volunteers may benefit from more immediate health information and guidance that will be passed on to providers without researchers knowing who the data belongs to. Learn more about the Generations Project.
DNA Diagnostics Lab
The Yale University DNA Diagnostics Laboratory is a College of American Pathologists and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory with decades of experience in the molecular diagnosis of genetic disease. The DNA Diagnostics Laboratory provides molecular diagnostic testing for a variety of genetic diseases. As technology progresses, their goal is to provide comprehensive testing by phenotype, that is to offer complete molecular testing for a given genetic disease state. In this way, more patients will receive the best care possible based on their unique genetic makeup. Learn more about the DNA Diagnostics Laboratory.
Programs and Trials The Pediatric Genomics Discovery Program (PGDP) seeks to discover the genes that cause childhood diseases. PGDP is a partnership between Yale New Haven Children’s Hospital and Yale Medicine and offers patients and their families an opportunity to be thoroughly examined by a team of physician-researchers in order to uncover the genetic cause of a rare or undiscovered disease. Some of these discoveries will guide us towards giving children the best medical care possible. Researchers intend to discover new ways to detect, treat, and maybe even prevent or cure childhood illnesses. Read more about The Pediatric Genomics Discovery Program (PGDP).
NICU Testing
There are many different causes of rare diseases, including infection, environmental factors, and genetics. There are an estimated 7,000 different rare diseases.
To improve the diagnosis and clinical care of critically ill infants and children, Yale School of Medicine’s departments of genetics and pediatrics, in collaboration with Yale New Haven Hospital, developed a rapid whole-genome sequencing test to be applied to “mystery diseases” in the pediatric intensive care units. Many illnesses in newborns and very young children have genetic underpinnings and establishing a diagnosis can guide medical management. The whole genome test, which utilizes services of the Yale Center for Genome Analysis, can be completed in a matter of days, in contrast with standard genetic testing which often takes a month or more.
Zebrafish Phenotyping Core for Precision Medicine
The Zebrafish Phenotyping Core for Precision Medicine seeks to model human diseases in zebrafish with the long-term goal of facilitating small molecule screens for novel therapies. Many genes, pathways, and processes are conserved between zebrafish and human, which along with its small size, rapid life-cycle, and extensive genetic tools, make zebrafish an ideal system in which to model many rare diseases and perform drug screening. Read more about the Zebrafish Phenotyping Core.
Education and Outreach Because rare diseases span all medical specialties, it is important that providers have an ongoing conversation about genetics and the human genome, and a deep understanding of the latest technologies and approaches to discover and diagnose rare disease. At any time, an internist, cardiologist, pulmonologist, radiologist, orthopedist, endocrinologist, neurologist, hematologist, oncologist, or any number of other specialists might encounter a patient who has a rare disease, identified or not. The Yale Department of Genetics is committed to the ongoing education of the rare disease community at Yale, and recently presented the Walter J. Burdette Trainee Symposium on Human Genomics, featuring speakers from several institutions. The next day, a Walter J. Burdette Workshop on Rare Disease Analysis provided training in sequencing, analysis, interpretation, data sharing and more. On February 28, the Yale School of Medicine will host a Dean’s workshop on Modeling Human Disease Using the Yale Zebrafish Phenotyping Core. Yale scientists also play a vital role in educating the community and policy makers on the importance of genomic health and precision medicine.
More Research at Yale School of Medicine
Yale Researchers Identify Rare Inherited Immune Disease
When a 9-year-old girl with anemia, breathing problems, and recurrent infections sought help for her mysterious ailments, Yale researchers and their collaborators at the National Institutes of Health sequenced her genes to pinpoint a cause. What they discovered was not only a new disease but unexpected new roles for a gene that affects the immune system. Learn more about the gene sequencing that solved this medical mystery.
Fighting for the Right Treatment for a Rare Reproductive Cancer
Ms. Di Gioia’s survival of a rare endometrial cancer had little to do with miracles, and everything to do with a novel treatment regimen developed by Dr. Santin at Smilow Cancer Hospital, a regimen that nearly didn’t see the light of day.
Yale Researchers Crack the Code of a Rare, Inherited Anemia
Patients in a Yale study present with a rare intron mutation that explains their disease and will lead to updates in diagnostic gene panels.
Possible Treatment for a Rare Vascular Disease In individuals with a rare genetic disorder that affects blood vessels, arteries and veins develop abnormal connections, causing bleeding in the skin, nose, and other organs. In most cases, the condition — hereditary hemorraghic telangiectasia, or HHT — is due to mutations in two genes that regulate proteins in the endothelial cells lining the blood vessels. Treatment options are limited.