42 research outputs found
Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders
Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3'UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease
Utilisation digestive apparente des acides aminés de quelques aliments chez le rat en croissance
National audienc
Utilisation digestive apparente des acides aminés de quelques aliments chez le rat en croissance
National audienc
EFFET DE L'INSULINE SUR LA COMPOSITION CORPORELLE ET LES TENEURS EN ACIDES AMINÉS LIBRES DU SANG, DU FOIE ET DU MUSCLE DU RAT EN CROISSANCE SOUMIS A UNE RESTRICTION ÉNERGÉTIQUE
International audienc
INFLUENCE DE LA SUPPLÉMENTATION EN LYSINE D'UN ALIMENT D'ALLAITEMENT SUR LA TENEUR EN LYSINE LIBRE DU SANG ET DU MUSCLE DU VEAU PRÉRUMINANT
International audienc
INFLUENCE DE LA TENEUR EN URÉE DU RÉGIME SUR L'AMINOACIDÉMIE LIBRE DE CHEVRES EN LACTATION
International audienc
Variations de l'insulinémie chez la brebis en fin de gestation et début de lactation. Influence de l'état nutritionnel en fin de gestation
International audienc
Altered response of protein synthesis to nutritional state and endurance training in old rats
International audienc