Characterizing Regulator Mechanisms in Spastic Paraplegia

Transcriptional and miRNA Regulation in the Spastic Paraplegias

The major goals of this project were to characterize the transcriptional and miRNA regulatory mechanisms for the 24 cloned SPG loci and to use the regulatory signatures to predict top candidate genes for the ~25 uncloned SPG loci. Subsequent to our identification of NIPA1 mutations in spastic paraplegia type 6 (SPG6), we characterized transcriptional and miRNA regulation in the spastic paraplegias, beginning with work we published on SPAST, the gene most frequently mutated in hereditary spastic paraplegia, and continuing to identification of regulation of over one-third of spastic paraplegia genes by a single miRNA operon.

Source(s) of Support

Spastic Paraplegia Foundation

Principal Investigator

Robert D. Nicholls, PhD