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Association of clock gene variants with Autism Spectrum Disorder in South Indian population
© Alex et al; licensee BioMed Central Ltd. 2014
Published: 21 January 2014
Autism Spectrum disorder is a group of neurodevelopmental disorders that manifests in the first three years of life. Social impairments, communication difficulties and repetitive/stereotyped behaviour are the common symptoms of the spectrum. One of the major endophenotype associated with the disease is circadian and sensory dysfunction. Circadian dysfunction is mainly observed by difficulties in sleeping. Around 56-83% of patients with ASD suffer from sleep problems. There is an endogenous circadian clock that regulates the sleep and wakefulness, cognitive function, systematic hormonal release and body temperature. We hypothesize that the genes functioning to maintain this molecular clock may be associated with ASD either directly or by its transcriptional regulation of other genes.
Materials and methods
The study population was from the Malayalam speaking population of Kerala. The patients were diagnosed and characterized based on DSM-IV criteria. We selected 2 genes which are core clock components, hCLOCK and PER3 due to its functional relevance. The CLOCK gene is the first essential component of the mammalian clock and was found to be associated with circadian rhythm sleep disorders. PER3 gene is implicated in delayed sleep phase syndrome and extreme diurnal preference. Single Nucleotide Polymorphisms in both genes were studied for association with the disease. Genotyping was done by sequencing and PCR RFLP.
Results and conclusion
Genotypic and allelic frequencies of the SNPs studied were analyzed to understand if there exists an association with the disease. We could not find any association with the 8 polymorphisms screened in hCLOCK gene in our population. However we were able to get an association with a VNTR in PER3 gene, with the 5 repeat allele being the risk allele. This is also the first report of PER3 gene being associated with ASD.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.