Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes

Chun Yen Lin; Kai Wei Chang; Chia Yi Lin; Jia Ying Wu; Hilary Coon; Pei Hsin Huang; Hong Nerng Ho; Schahram Akbarian; Susan Shur Fen Gau; Hsien Sung Huang

doi:10.1038/s41598-018-22753-4

Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes

Chun Yen Lin
, Kai Wei Chang
, Chia Yi Lin
, Jia Ying Wu
, Hilary Coon
, Pei Hsin Huang
, Hong Nerng Ho
, Schahram Akbarian
, Susan Shur Fen Gau
, Hsien Sung Huang

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English
Article number	4277
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-22753-4
State	Published - 1 Dec 2018

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Lin, C. Y., Chang, K. W., Lin, C. Y., Wu, J. Y., Coon, H., Huang, P. H., Ho, H. N., Akbarian, S., Gau, S. S. F., & Huang, H. S. (2018). Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes. Scientific Reports, 8(1), Article 4277. https://doi.org/10.1038/s41598-018-22753-4

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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\}",

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AU - Lin, Chun Yen

AU - Chang, Kai Wei

AU - Lin, Chia Yi

AU - Wu, Jia Ying

AU - Coon, Hilary

AU - Huang, Pei Hsin

AU - Ho, Hong Nerng

AU - Akbarian, Schahram

AU - Gau, Susan Shur Fen

AU - Huang, Hsien Sung

PY - 2018/12/1

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N2 - 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.

AB - 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.

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ER -

Allele-specific expression in a family quartet with autism reveals mono-to-biallelic switch and novel transcriptional processes of autism susceptibility genes

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