Christel Depienne,  Institut für Humangenetik, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen

Systematic identification of noncoding tandem repeat expansions in unresolved cases of spastic paraplegias and spinocerebellar ataxias using a combination of short- and long-read sequencing technologies

Genetic tests developed so far have mainly focused on coding regions of the genome i.e. parts of the genes that correspond to the sequence of the protein(s) they encode. However, these tests only permit to find the cause responsible for genetic disorders in less than half of the patients. An abundant source of variation in the human genome is constituted by unstable repeated DNA elements known as tandem repeats or microsatellites. The expansion of the number of repeated elements has been known to cause genetic disorders for more than 30 years but because these repeats are very abundant and variable in the normal population, making their analysis extremely challenging, they are almost completely ignored in current genetic tests. In this project, we propose to search for novel repeat expansions in 16 patients with hereditary spastic paraplegia or cerebellar ataxia in whom current genetic tests have failed to identify a genetic cause using a combination of novel sequencing technologies.