@article{7ab865ae9436465aa7e8294a83dd7a13,
title = "Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes",
abstract = "Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and the exact causal mechanism is unknown. Dysregulated allele-specific expression (ASE) has been identified in persons with ASD; however, a comprehensive analysis of ASE has not been conducted in a family quartet with ASD. To fill this gap, we analyzed ASE using genomic DNA from parent and offspring and RNA from offspring's postmortem prefrontal cortex (PFC); one of the two offspring had been diagnosed with ASD. DNA- and RNA-sequencing revealed distinct ASE patterns from the PFC of both offspring. However, only the PFC of the offspring with ASD exhibited a mono-to-biallelic switch for LRP2BP and ZNF407. We also identified a novel site of RNA-editing in KMT2C in addition to new monoallelically-expressed genes and miRNAs. Our results demonstrate the prevalence of ASE in human PFC and ASE abnormalities in the PFC of a person with ASD. Taken together, these findings may provide mechanistic insights into the pathogenesis of ASD.",
author = "Lin, {Chun Yen} and Chang, {Kai Wei} and Lin, {Chia Yi} and Wu, {Jia Ying} and Hilary Coon and Huang, {Pei Hsin} and Ho, {Hong Nerng} and Schahram Akbarian and Gau, {Susan Shur Fen} and Huang, {Hsien Sung}",
note = "Funding Information: This work was supported by the Ministry of Science and Technology, Taipei, Taiwan (MOST 105-2628-B-002-033-MY3 to H-S.H), the National Health Research Institutes, Miaoli, Taiwan (Career Development Grant, NHRI-EX103-10316NC to H-S.H.), the National Taiwan University, Taipei, Taiwan (AIM for Top University Excellent Research Project, 102C101-42, 103C101-C1 and 104C101-B1 to S.S.G. and H-S.H), the National Taiwan University Hospital (NTUH-UN104-018, NTUH-UN105-014 and NTUH-UN106-011 to S.S.G. and H-S.H.), the Foundation for the Advancement of Outstanding Scholarship, Taipei, Taiwan (Young Scholars{\textquoteright} Creativity Award, to H-S.H), the intramural funding of Genomics Research Center, Academia Sinica, Taiwan and the Ministry of Science and Technology, Taiwan (MOST 103-2628-B-001-001-MY4 to T-J.C). We are grateful for support from the participating family as well as to Jane Pickett at Autism BrainNet for coordinating the pooling of blood-and brain-derived genetic material. We thank Trees-Juen Chuang for valuable reading of the manuscript. We thank Boting Wang for their experimental help. We would like to acknowledge Autism BrainNet, sponsored by the Simons Foundation and Autism Speaks, for providing biological material. Brain specimens were acquired through the Autism Tissue Program, a predecessor to Autism BrainNet, from the Harvard Brain Tissue Resources Center (McLean Hospital, Belmont, MA, USA) for the Autism Tissue Program, a predecessor to Autism BrainNet. Samples and family diagnostic data were originally collected by the University of Utah Autism Research Program (Hilary Coon) supported by RO1MH094400. Samples and data were made available through collaboration with this project and with additional direct permission from the family. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-22753-4",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}