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Autism and Single Nucleotide Polymorphisms in the IGF Pathway

This project’s goal was to test the frequencies of single nucleotide polymorphisms (SNPs) in selected genes that populate the IGF-1, mTor and p53 interrelated signal transduction pathways in individuals with autism spectrum disorder. The IGF-1, mTor and p53 networks are known to act in the central nervous system (CNS) and regulate cell growth and size, dendrite formation, metabolic capabilities, glucose and amino acid use, stress and cell/DNA damage. It has become apparent that there are connections between the IGF-1-PI3K-AKT (cell growth, anti-apoptotic), mTor (glucose and amino acid sensing, autophagy control, metabolic regulation) and the p53 (stresses of many kinds-oxidative, hypoxia, DNA damage, etc. leading to apoptosis and senescence) pathways. These three inter-related networks play a role in cancer; they are involved in diabetes and glucose utilization by cells, and they affect longevity. Several lines of evidence suggest that this same critical set of genes can act in the CNS to contribute to autism. For example, 60% of individuals with either TSC-1 or TSC-2 mutations have autism; some individuals with mutations in the PTEN gene develop autism, and a knock-out of the PTEN gene activity in the CNS of mice alters the structure of the CNS and results in behavioral abnormalities in these mice. Thus, the genes in these networks are interesting candidates whose alleles might contribute to autism or ASD. Initially, the PIs examined possible increased frequencies of SNPs and haplotypes from each gene separately. Later, combinations of SNPs, haplotypes and genes were examined for enhanced frequency in the autistic group.  Looking for polymorphisms in these candidate genes could complement other ongoing studies to track down mutations that contribute to autism spectrum disorder.