In–Silico Visualization of Gene-Gene Interactions in Autism Spectrum Disorder Genes

Abstract

ABSTRACT: Autism spectrum disorder is a group of neurodevelopmental disorders with still unknown causative mechanisms. Recent findings implicate a complex etiology with multiple genetic and epigenetic factors. The disruption of vital gene-gene interactions has been proposed to be one of the contributing factors for the disease. NPAS (neuronal PAS domain proteins 1 and 3) have been recognized as critical regulators of neuropsychiatric development and function. In the present study, a genetic network association with NPAS3 and the highest interacting gene CRKL has been mapped for ASD and analyzed to decipher the complex genetic basis of Autism spectrum disorder. CRKL encodes a protein kinase with SH2 and SH3 (SRC homology) domains which activate RAS and Jun signaling pathways. The CRKL gene sequence was retrieved and compared using BLAST homology search. The physiological and chemical features of CRKL protein was studied using Uniprot Database and Protparam followed by homology modelling by constructing a phylogenetic. Physio-chemical properties of CRKL protein was studied by Protparam which gave insight into the role of other interacting proteins involved in this process. Further analysis, a conserved region of intersecting protein of CRKL were identified using multiple sequence alignment. The gene interactions data revealed that CRKL as one of the key genes associated with Autism spectrum disorder. CRKL defects in the deleted region of 22q11. 2 of the human chromosome 22 have a strong correlation with several of the birth defects as it can hamper the development of the brain along with behavior and cognitive function. This may lead to neurodevelopmental disorders like autism spectrum disorder or schizophrenia, depending on which particular region in the gene is affected. CRKL gene could be a potential biomarker for many In-borne diseases. An investigation in current study was done to find out the genetic network and decipher the complex genetic basis of Autism spectrum disorder.