Research project - DenovoRank

Whole genome analysis in individuals with neurodevelopmental disorders (NDD), including intellectual disability (ID), can reveal genetic variations responsible for their condition in approximately 60% of cases. While some types of variations with major consequences are relatively easy to interpret, others are more difficult to analyze because their impact is less predictable. More than two-thirds of the variations involved in certain NDDs, such as intellectual disability, are found in the affected individual but are absent from their parents’ genomes (de novo variants). However, with each generation, the number of de novo variations is relatively small (~80–120), compared to the total number of variants typically found in a human genome (~5 million).

We therefore aim to focus on the de novo variants identified in patients, study their distribution across the genome, and annotate them to identify those that may have functional consequences. In particular, we aim to identify synonymous variants and assess their effects on splicing and their impact on protein translation as part of a research project funded by the ANR (Synovar, coord.: M. de Tayrac). We will also pay special attention to rare variants occurring on the X chromosome in male patients.