Genomic neighborhoods and inherited disease: the case for SIOD

While completing medical training in clinical genetics, Dr. Cornelius Boerkoel was consulted on two patients with a rare disease called Schimke immuno-osseous dysplasia (SIOD). At the time, there was little known about the disease, other than that it involved kidney failure and abnormal bone growth causing short height. Dr. Boerkoel’s early research in this area highlighted several previously unknown features of this disease, including the cause of SIOD: mutations (alterations) in both copies of a gene named SMARCAL1. He has also shown that SIOD arises from abnormal activity across most genes. Working with fly and mouse models that he developed to study SIOD, Dr. Boerkoel has created a model for studying how many small alterations in gene expression can cause disease.

Since common diseases such as atherosclerosis, stroke, endocrine dysfunction, immunodeficiency, and poor growth are all features of SIOD, this research is relevant to a better understanding of various unstudied mechanisms underlying these common diseases in the general population. To continue this work, Dr. Boerkoel will complete characterization of the function of SMARCAL1 using biochemical, fruit fly and mouse studies. He will test whether hormone supplementation might be an effective treatment for SIOD. Dr. Boerkoel will also determine whether the gene expression changes observed in SIOD are a feature in other patient populations affected with diseases also found in SIOD. This research will develop a new and unique model for understanding how changes in gene expression can predispose individuals to disease.