Creation of a Schwann Cell Gene Regulatory Network

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Abstract. The peripheral neuropathy known as Charcot-Marie-Tooth Disease (CMT1A) is one of the most common heritable disorders in the nervous system, affecting 1 in 2500 individuals. Tremendous progress has been made in identifying structural and coding variants that cause this disease, with over 100 genes having mutations associated with CMT. However, a substantial number of individuals do not have a definitive genetic diagnosis. The goal of this project is to develop a comprehensive Schwann cell gene regulatory network model incorporating experimental data on peripheral nerve with ChIP-seq analyses of TF binding as well as epigenomic annotations from human peripheral nerve that have recently become available. The model will incorporate data showing the dynamics of Schwann cell enhancers that have been shown to become dynamically regulated after peripheral nerve injury. Moreover, the model will be validated in its ability to identify key regulatory elements using eQTL analysis. Development of a Schwann cell network model with sufficient resolution to determine effects on individual enhancers and TF binding sites will be developed for eventual application to WGS analysis of patient data with peripheral neuropathy, including not only CMT but also other disorders affecting the peripheral nervous system.