Adolescent Idiopathic Scoliosis (AIS) is a disease of the spine, affecting between 1-3% of the population. This disease manifests as a lateral curvature of the spine that can lead to a range of conditions such as back pain and respiratory issues. Recent advances in genomics have allowed researchers to identify variations in the genomes of affected individuals associated with AIS. Several single nucleotide polymorphism (SNP) identified are linked to the transcription factor Ladybird Homeobox 1 (LBX1) gene, which is important for development of limb muscles and the dorsal spinal cord. We are focussing on rs11190870, a SNP which has been verified to be significant in multiple cohorts.
The aim of my research is to begin to understand the molecular basis that underlies the pathology of AIS associated SNPs. This will allow us to establish a genetic model for LBX1-associated AIS.
The three main methods of my investigation are ChIP-qPCR, RT-qPCR and in situ hybridisation. These techniques allow me to investigate interactions between Lbx1 and potential regulators of Lbx1 mRNA, and whether these potential regulators are binding the region surrounding SNP rs1190870 in the dorsal spinal cord of mice.
We anticipated Pbx1/Pbx3 to regulate Lbx1 mRNA, this has been found to not be the case. I am currently exploring other potential regulators of Lbx1. Initial findings show that EZH2 appears to be binding at SNP rs1190870.