Since 2008, we have sought to produce exome sequencing protocols with the best quality for the identification of rare mutations, namely a WES with high depth of coverage (> 100×) and with a limitation of gaps of sequencing (which directly depends on hybridization capture brand and know-how).
This strategy allowed us to rapidly demonstrate that a WES of good quality should replace Sanger sequencing for the molecular diagnosis of monogenic disorders in a near future.
This study was published in PLoS One. : « Molecular Diagnosis of Neonatal Diabetes Mellitus Using Next-Generation Sequencing of the Whole Exome »
Furthermore, this strategy allowed us to identify novel mutations/genes involved into monogenic forms of diabetes:
- KCNJ11 dans les formes « MODY » : « Whole-Exome Sequencing and High Throughput Genotyping Identified KCNJ11 as the Thirteenth MODY Gene »
- GATA6 dans le diabète néonatal et familial : « GATA6 inactivating mutations are associated with heart defects and, inconsistently, with pancreatic agenesis and diabetes »