The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism
作者： Dexter Hadley , Zhi-liang Wu , Charlly Kao , Akshata Kini , Alisha Mohamed-Hadley
DOI: 10.1038/NCOMMS5074
关键词: Genetics 、 Autism 、 Gene family 、 Metabotropic glutamate receptor 、 Biology 、 Schizophrenia 、 Druggability 、 Metabotropic glutamate receptor 3 、 Gene 、 Gene regulatory network
摘要: Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful target large gene families drug binding sites. Here we search family interaction (GFINs) in 6,742 patients ASDs relative to 12,544 neurologically normal controls, find potentially druggable targets. We significant enrichment structural defects (Pr2.40E � 09, 1.8-fold enrichment) metabotropic glutamate receptor (GRM) GFIN, previously observed impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, MXD-MYC-MAX network genes, implicated cancer, is significantly enriched (Pr3.83E 23, 2.5-fold enrichment), as calmodulin 1 (CALM1) (Pr4.16E 04, 14.4-fold which regulates voltage-independent calcium-activated action potentials at neuronal synapse. interactions presenting new translational opportunities explore therapeutic interventions.
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