Understanding non-coding genomic variation in neurological disorders

The vast majority of DNA is made up of non-coding sequences that do not encode for protein sequences. In the past, non-coding regions of DNA were difficult to analyse due to large repetitive sections and areas of very similar DNA sequences. These restrictions have largely been overcome, and we have highlighted the importance of non-coding regions to disease with the identification of major causes of neurological disease. We plan to investigate four large diverse groups of patients and families with neurological disorders. We will examine the non-coding part of DNA in these groups, initially using traditional genome sequencing but with optimised and newly developed methods. To overcome previous difficulties with non-coding genome sequencing we will use the recently developed techniques of long-read genome sequencing and high-resolution-maps of single-stained DNA molecules Finally, we will comprehensively interpret and sequence RNA from patients to help prove the defects found in the non-coding DNA.