Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes
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Copy number variation has emerged as an important cause of phenotypic variation, particularly in relation to some complex disorders. Autism spectrum disorder (ASD) is one such disorder, in which evidence is emerging for an etiological role for some rare penetrant de novo and rare inherited copy number variants (CNVs). De novo variation, however, does not always explain the familial nature of ASD, leaving a gap in our knowledge concerning the heritable genetic causes of this disorder. Extended pedigrees, in which several members have ASD, provide an opportunity to investigate inherited genetic risk factors. In this current study, we recruited 19 extended ASD pedigrees, and, using the Illumina HumanOmni2.5 BeadChip, conducted genome-wide CNV interrogation. We found no definitive evidence of an etiological role for segregating CNVs in these pedigrees, and no evidence that linkage signals in these pedigrees are explained by segregating CNVs. However, a small number of putative de novo variants were transmitted from BAP parents to their ASD offspring, and evidence emerged for a rare duplication CNV at 11p13.3 harboring two putative ‘developmental/neuropsychiatric’ susceptibility gene(s), GSTP1 and NDUFV1.
KeywordsAutism Spectrum Disorder Autism Spectrum Disorder Copy Number Variant Intellectual Disability Autism Spectrum Disorder Diagnosis
We thank the families for their participation in the study and The Centre for Applied Genomics at the Hospital for Sick Children and University of Toronto for technical support. MWS acknowledges the support of CIHR [Strategic Training in Advanced Epidemiology (STAGE) program], Hamilton Health Sciences, and Scottish Rite Charitable Foundation. This work was funded in part by CIHR operating grants #79499 and #89777, NIH grants MH076028, HD003110 (JP) and MH086117 (VJV). SWS holds the GlaxoSmithKline-CIHR Endowed Chair in Genome Sciences. PS holds the Patsy and Jamie Anderson Chair in Child and Youth Mental Health.This study makes use of data generated by the DECIPHER Consortium. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from firstname.lastname@example.org. Funding for the project was provided by the Wellcome Trust.
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