The Utah Population Database (UPDB) is the world's largest, most comprehensive population database containing medical records and pedigrees that are at high-risk for inherited disorders, offering unparalleled opportunities to identify genetic causes of disease. Together with partner institutions - including Washington University, the Chan Soon-Shiong Family Foundation and Chan Soon-Shiong Institute of Advanced Health, and Regeneron Genetics Center, a wholly owned subsidiary of Regeneron, Inc. - the Utah Genome Project is sequencing and analyzing the genomes of over 6,000 individuals represented within the UPDB. The goal is to speed development of preventative therapies, diagnostics, and treatments for over 24 conditions that impact people across the world, including:
Cancers are caused by changes in the DNA of tumor cells. This means that cancer genomes are different from an individual's inherited, or germline, genome. The joint analyses of germline and cancer genomes from members of a high-risk CLL Utah pedigree will answer critical questions in cancer genomics and will fuel development of novel software to analyze cancer genomes.
Patients with Chronic Myelomonocytic Leukemia (CMML) have a very poor prognosis due to limited efficacy of current treatments. Researchers are identifying novel genetic changes in CMML that can be rationally targeted by drugs or can help to predict the best treatment or outcomes.
About 1/3 of individuals with prostate cancers develop recurrent/metastatic disease and eventually die from their prostate cancer. Multiple related cases of lethal prostate cancer have been found in extended Utah pedigrees that show a significant excess of prostate cancer. This project aims to identify predisposition genes or variants for the most serious cases of prostate cancer via the sequencing of related lethal prostate cancer cases with strong family history.
Atrial Fibrillation (AF) is an irregular heartbeat associated with heart failure and stroke that is often left undiagnosed, leading to sudden medical crisis or death. With early diagnosis, prevention, and treatment with medications, these fates can be avoided. This project aims to sequence three large families to identify causative genes of AF.
Common variable immune deficiency (CVID) causes dangerously low levels of infection-fighting antibodies that, if left untreated, leads to recurrent infections. The “variable” in the name refers to the fact that more than 10 different mutations have so far been found to trigger the disease, though they only account for 10-20 percent of cases. This project is designed to discover new mutations that cause CVID in the vast majority of patients.
The goal of this project is to identify genetic variants that cause severe, atypical immune-mediated diseases (IMDs) that defy categorization, and to identify and characterize genetic variants in families with inherited IMDs. A better understanding of the causes of IMDs will provide valuable insights into treating debilitating conditions such as Crohn, arthritis, and ulcerative colitis.
Obesity in the United States is reaching epidemic proportions, bringing with it a rise in associated health conditions, and a significant financial burden. This project will compare the genomes of 40 "healthy thin" and 20 overweight individuals to identify obesity resistance genes which may lead to new approaches to obesity control.
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's Disease, is a progressive neurodegenerative disorder, often causing total paralysis, for which there is no cure. The goal of this project is to identify novel mutations contributing to familial ALS using a combination of high-risk pedigrees from the UPDB and, with consent, samples from patients of University Health Care’s ALS multidisciplinary clinic.
Spontaneous preterm births (SPTB) account for 70% of neonatal death and result in billions of direct health care costs. Treatment with progesterone can prevent SPTB; however, not all women respond to treatment. This project seeks to identify genetic factors that determine response versus nonresponse to progesterone treatment, a step toward individualizing preterm birth interventions.
In the U.S., more than 12% of babies are born preterm, and the rate continues to rise. Despite the magnitude of the problem, the causes for preterm birth are not well understood. This project will sequence 70 women in families at high risk for spontaneous preterm birth (SPTB) to identify common and rare genetic causes for the condition.