Abstract
BackgroundCopy number variations (CNVs) and DNA sequence alterations affecting specific neuronal genes are established risk factors for Autism Spectrum Disorder (ASD). In what is largely considered a genetic condition, so far, these mutations account for ~20% of individuals having an ASD diagnosis. However, non-coding genomic sequence also contains functional elements introducing additional disease risk loci for investigation.ResultsWe have performed genome-wide analyses and identified rare inherited CNVs affecting non-genic intervals in 41 of 1491 (3%) of ASD cases examined. Examples of such intergenic CNV regions include 16q21 and 2p16.3 near known ASD risk genes CDH8 and NRXN1 respectively, as well as novel loci contiguous with ZHX2, MOCS1, LRRC4C, SEMA3C, and other genes.ConclusionsRare variants in intergenic regions may implicate new risk loci and genes in ASD and also present useful data for comparison with coming whole genome sequence datasets.
Highlights
Copy number variations (CNVs) and DNA sequence alterations affecting specific neuronal genes are established risk factors for Autism Spectrum Disorder (ASD)
A total of 212 non-coding genomic regions were determined as harboring overlapping CNVs in two or more unrelated ASD cases that were absent in control samples
We find CNVs both upstream (e.g. UNC5D (Figure 1C), MOCS1, ASTN2, SEMA3C, ZHX2, LUZP2, CDH8) and downstream (C3orf58, RXRA, MRGPRD) of known ASD risk genes and putative novel loci
Summary
Copy number variations (CNVs) and DNA sequence alterations affecting specific neuronal genes are established risk factors for Autism Spectrum Disorder (ASD). In what is largely considered a genetic condition, so far, these mutations account for ~20% of individuals having an ASD diagnosis. Non-coding genomic sequence contains functional elements introducing additional disease risk loci for investigation. Newer genomic technologies like high-resolution microarrays and generation exome sequencing have enabled the identification of many clinically relevant genetic variants for both Mendelian and complex disorders. For many conditions the identified genes account for only a proportion of heritability. This observation coupled with the recognition of the functional relevance of non-genic regions [1] target these genomic segments as candidates for investigation for a role in disease. Analyses of rare (
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
