UC Santa Cruz

An increased risk of diabetes has been observed among Huntington’s disease (HD) carri- ers, but there has not been follow-up investigation of the genetic nature of the risk. Here, we investigated diabetes phenotypes signatures in gene expression, DNA polymorphisms and intracellular glucose levels comparing rat and human data. Using a genome-wide association study (GWAS), RNA sequencing (RNA-Seq) analysis, and western blotting of Rattus norvegicus and human, we were able to identify a correlation between HD and DNA polymorphisms in the family of sortilins, tetraspanins and HLA/MHC proteins. We were also able to correlate SNP variants and gene expression with intracellular glu- cose levels using the nanopipette platform. Our results suggest that ST14A cells, from R. norvegicus, are a reliable model of HD, because they allowed confirmation of markers of diabetes, such as sortilins, glucose transporters and MHC proteins in our cell model. This model allowed experiments that highlight genes involved in mechanisms targeted by diabetes drugs, such as glucose transporters, and proteins controlling insulin release, related to mHTT. To the best of our knowledge, this is the first GWAS study using RNA-Seq data from both ST14A rat HD cell model and human HD. Similarly, for the first time, glucose levels were detected at the single-cell level in a HD model using nanopipettes.