PT  - JOURNAL ARTICLE
AU  - Thomas R. Ward
AU  - Xianglong Zhang
AU  - Louis C. Leung
AU  - Bo Zhou
AU  - Kristin Muench
AU  - Julien G. Roth
AU  - Arineh Khechaduri
AU  - Melanie J. Plastini
AU  - Carol Charlton
AU  - Reenal Pattni
AU  - Steve Ho
AU  - Marcus Ho
AU  - Yiling Huang
AU  - Joachim F. Hallmayer
AU  - Phillippe Mourrain
AU  - Theo D. Palmer
AU  - Alexander E. Urban
TI  - Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model
AID  - 10.1101/2020.02.09.940965
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.09.940965
4099  - http://biorxiv.org/content/early/2020/02/10/2020.02.09.940965.short
4100  - http://biorxiv.org/content/early/2020/02/10/2020.02.09.940965.full
AB  - Copy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.