Paul Lockhart (Associate Professor, Co-Director Department of Genetics, Bruce Lefroy Centre, Murdoch Children’s Research Institute, Royal Children’s Hospital, Victoria, Australia)
As a geneticist, Dr Paul Lockhart outlined revolutionary approaches in technology that has led to identifying the genetic causes of many developmental disorders, including ACC. There are about 6,000 different conditions described in literature, but scientists only know the genetic basis for about half of them. There have been remarkable breakthroughs in methodologies (e.g., high-density microarrays, next-generation sequencing), which have resulted in the “golden-age” of gene discovery. Analyses, which used to take weeks to process, can now take half-an-hour at a much-reduced cost.
There are still many challenges in the field and finding a causative change can be difficult. Detecting an alteration in a single gene is said to be equivalent to finding a single typo in 300 copies of the entire Harry Potter series! There are also natural variations found in everyone’s genes, and most are not related to a condition. In order to confidently state that a particular gene is likely to be the cause, scientists need to match up gene mutations and symptoms across several children to find common features. There are now large population databases available, where thousands of individuals have had their genes sequenced. Multiple comparisons can therefore be made that will add to the certainty of diagnosis. One such study based in the UK, Deciphering Developmental Disorders (DDD), has been extremely successful in advancing clinical genetic practice for children with developmental disorders. Although data collection has ended, analysis from the DDD study is on-going and over 30 new genetic conditions have been identified from analysing samples from over 13,000 families.
Dr Lockhart is confident that understanding the genetic basis of disorders is the key to personalised medicine. It will enable families to have more accurate information on diagnosis and outcome, as well as provide the opportunity to develop targeted treatments in the future.