Project description:Next-generation sequencing (NGS) has supported precision therapeutic approaches that have improved the lives of children with rare diseases. Patients with congenital diarrhea and enteropathies (CODE) have a particularly difficult disease with high morbidity and mortality. However, there are now several targeted therapies including specific diets, pharmacological treatments, and surgical interventions that are based on an individual’s genetic diagnosis. We performed NGS on a large cohort of 139 infants with suspected monogenic congenital diarrheal disorders and identified known causal variants in 50% of cases, including a new founder NEUROG3 variant. We also uncovered and functionally characterized three novel CODE genes, GRWD1, MYO1A, and MON1A, using cell and zebrafish models.
Project description:We have used DGE-SAGE, a digital transcriptomics tool, to determine the expression profile of E14.5 mouse forelimbs and hindlimbs. The forelimb, hindlimb developmental lag combined with the analysis of these datasets allow us a better insight into the dynamics of the limb growth genetic network, in particular the characterisation of genes that are differentially expressed and are putative modulators of limb growth and or candidates for limb malformation syndromes. Conclusions: The datasets and results presented in this study allow us to extend the current knowledge of the limb development and constitute an extremely relevant resource for research into the genetics of organ growth and thus ontogenesis. DGE-SAGE expression profiles for E14.5 mouse forelimb and hindlimb