Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing

Jiang, Yong-hui, Yuen, Ryan K. C., Jin, Xin, Wang, Mingbang, Chen, Nong, Wu, Xueli, Ju, Jia, Mei, Junpu, Shi, Yujian, He, Mingze, Wang, Guangbiao, Liang, Jieqin, Wang, Zhe, Cao, Dandan, Carter, Melissa T., Chrysler, Christina, Drmic, Irene E., Howe, Jennifer L., Lau, Lynette, Marshall, Christian R., Merico, Daniele, Nalpathamkalam, Thomas, Thiruvahindrapuram, Bhooma, Thompson, Ann, Uddin, Mohammed, Walker, Susan, Luo, Jun, Anagnostou, Evdokia, Zwaigenbaum, Lonnie, Ring, Robert H., Wang, Jian, Lajonchere, Clara, Wang, Jun, Shih, Andy, Szatmari, Peter, Yang, Huanming, Dawson, Geraldine, Li, Yingrui and Scherer, Stephen W. (2013) Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. American Journal of Human Genetics, 93 2: 249-263. doi:10.1016/j.ajhg.2013.06.012

Author Jiang, Yong-hui
Yuen, Ryan K. C.
Jin, Xin
Wang, Mingbang
Chen, Nong
Wu, Xueli
Ju, Jia
Mei, Junpu
Shi, Yujian
He, Mingze
Wang, Guangbiao
Liang, Jieqin
Wang, Zhe
Cao, Dandan
Carter, Melissa T.
Chrysler, Christina
Drmic, Irene E.
Howe, Jennifer L.
Lau, Lynette
Marshall, Christian R.
Merico, Daniele
Nalpathamkalam, Thomas
Thiruvahindrapuram, Bhooma
Thompson, Ann
Uddin, Mohammed
Walker, Susan
Luo, Jun
Anagnostou, Evdokia
Zwaigenbaum, Lonnie
Ring, Robert H.
Wang, Jian
Lajonchere, Clara
Wang, Jun
Shih, Andy
Szatmari, Peter
Yang, Huanming
Dawson, Geraldine
Li, Yingrui
Scherer, Stephen W.
Title Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2013-08-08
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2013.06.012
Open Access Status DOI
Volume 93
Issue 2
Start page 249
End page 263
Total pages 15
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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