Limb malformation syndromes are a common group of disorders. Club foot alone is seen in approximately one in 1,000 births. Managing these syndromes typically involves multiple surgical procedures, serial casting, and physical therapy. Because features of such syndromes overlap, clinical diagnosis is often problematic. This uncertainty compromises effective treatment. Our gene mapping research will: lead to more accurate diagnosis and better clinical management of these disorders, enable parents to make informed reproductive decisions, address fundamental questions about the biology of bone development.
Our evolutionary genetic research will shed light on the origin of our species. This topic has generated great interest for centuries, but only in the last decade have sufficient molecular genetic data been generated to help resolve questions regarding human origins. Our studies of human genetic variation will also increase our understanding of the distribution and prevalence of genetic diseases in populations.
The inflammatory bowel diseases including ulcerative colitis and Crohn disease are chronic inflammatory disorders of the gastrointestinal tract. The causes of these disorders are unknown. However, they tend to cluster in families, suggesting a genetic component to their etiology. Genetic risk factors have been identified, but do not entirely explain the observed familial clustering.
Our work is focused on understanding the familial clustering of the inflammatory bowel diseases. We use genealogic data that is linked to healthcare encounter data to understand how the inflammatory bowel disease clusters in families on a population level. We also enroll children in genetic studies of inflammatory bowel disease as well as their families. Our research questions include:
1. What is the recurrence risk of inflammatory bowel disease in extended Utah families?
2. How does age of inflammatory bowel disease onset change the way inflammatory bowel disease clusters in families?
3. What specific genetic variants explain familial clustering in large families?
The identification of molecular defects in primary immunodeficiency disorders have been the basis for discovery of key pathways in the immune system, as many of these disorders involve defects with simple Mendelian inheritance patterns. My research interest involves the use of microarray technology and next-generation sequencing methods to identify mutations in primary immunodeficiencies, as well as functional assays in human lymphocytes to characterize these defects. My current research focus is on the study of a rare immunodeficiency disorder known as multiple intestinal atresia with immunodeficiency. Infants born with this disorder have abnormal development of the gut at multiple locations, in addition to susceptibility to opportunistic infections. We are studying the genetic and molecular pathogenesis of this disorder, as well as investigating transplant outcomes in these children. I am also involved in the development of a severe combined immunodeficiency (SCID) newborn screening program for the state of Utah using a PCR-based assay for TRECs, or T cell receptor excision circles. The goal of this program is to identify SCID infants early, prior to the onset of infections, so they can be treated with life-saving hematopoietic stem cell transplantation.