Understanding the molecular basis of canvas-a novel neurological disorder caused by an expanded dna repeat

Summary Understanding the molecular basis of canvas-a novel neurological disorder caused by an expanded dna repeat

Project Details

Repeat expansions cause over twenty neurogenetic disorders of major clinical DNA repeat expansion mutations cause over twenty neurogenetic disorders of major clinical significance which can present with heterogenous, overlapping clinical phenotypes. Discovery of novel expansions and diagnostic testing of known loci has proven extremely challenging due to the repeat sequences being refractory to standard molecular techniques. We recently determined that a novel intronic pentanucleotide repeat expansion on chromosome 4 causes the neurogenetic disorder termed cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our preliminary studies suggest the expansion is the most common genetic cause of ataxia in humans.

This project will be a component of a larger study that aims to characterise the CANVAS repeat mutation using short read and long read gene Next Generation sequencing technologies. It will investigate pathogenic mechanisms underlying disease utilising molecular and cell biology techniques, including primary cell and induced pluripotent stem cell generation and characterisation. The candidate will also contribute to the gene discovery component of an ongoing trial testing the diagnostic utility of expansion repeat detection in next generation sequencing data.