Links between genetics and pathophysiology in the autism spectrum disorders.
Bottom Line: Significant collaborative effort has been made over the last 15 years in an attempt to unravel the genetic mechanisms underlying these conditions.This has led to important discoveries, both of the roles of specific genes, as well as larger scale chromosomal copy number changes.Here, we summarize some of the latest genetic findings in the field of ASD and attempt to link them with the results of pathophysiological studies to provide an overall picture of at least one of the mechanisms by which ASD may develop.
Affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, UK.Show MeSH
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Mentions: Candidate gene association analysis for ASD has been an extremely active field, with over two hundred genes examined in the last 15 years. Of these, approximately one hundred, spread across virtually every chromosome, are reported as showing at least nominal association with ASD (Sousa et al, 2011; Fig 1A), although this likely contains some false positive results. Tools such as the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 9.0 (http://string.embl.de/) have been developed, which show the potential interactions between the proteins encoded by these genes (Szlarczyk et al, 2010; Fig 1B). While many of these interactions are predicted using methods such as text mining, and therefore are likely to contain some false positive results, they do demonstrate both the connectedness and complexity that is likely to underlie susceptibility to ASDs. Despite these caveats, the importance of such candidate gene studies is clear, particularly in light of the difficulty for genome-wide association studies to detect weak effects. Candidate genes can be identified by different means, including function, linkage, and genome-wide association. Several examples highlight the benefits and difficulties of candidate gene studies in ASDs.
Affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, UK.