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Correction published on 18 October 2022, see Cells 2022, 11(20), 3276.
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Article

A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder

by
Jie Huang
1,2,†,
Jun Liu
1,3,†,
Ruiyi Tian
1,4,
Kevin Liu
1,
Patrick Zhuang
1,
Hannah Tayla Sherman
1,
Christoph Budjan
5,
Michelle Fong
1,
Min-Seo Jeong
1 and
Xue-Jun Kong
1,6,*
1
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
2
Department of Global Health, Peking University School of Public Health, Beijing 100871, China
3
Brigham Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4
Washington University in St. Louis, St. Louis, MO 63130, USA
5
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
6
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Cells 2022, 11(1), 10; https://doi.org/10.3390/cells11010010
Submission received: 23 September 2021 / Revised: 13 December 2021 / Accepted: 16 December 2021 / Published: 21 December 2021 / Corrected: 18 October 2022
(This article belongs to the Special Issue Molecular Genetics of Neuropsychiatric Diseases)
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Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients’ clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD.
Keywords: Autism Spectrum Disorder (ASD); whole genome sequencing; whole exome sequencing; sanger sequencing; genetic report; trios; pathogenic variants; bioinformatics pipeline; precision medicine; molecular diagnostics Autism Spectrum Disorder (ASD); whole genome sequencing; whole exome sequencing; sanger sequencing; genetic report; trios; pathogenic variants; bioinformatics pipeline; precision medicine; molecular diagnostics

Share and Cite

MDPI and ACS Style

Huang, J.; Liu, J.; Tian, R.; Liu, K.; Zhuang, P.; Sherman, H.T.; Budjan, C.; Fong, M.; Jeong, M.-S.; Kong, X.-J. A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells 2022, 11, 10. https://doi.org/10.3390/cells11010010

AMA Style

Huang J, Liu J, Tian R, Liu K, Zhuang P, Sherman HT, Budjan C, Fong M, Jeong M-S, Kong X-J. A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells. 2022; 11(1):10. https://doi.org/10.3390/cells11010010

Chicago/Turabian Style

Huang, Jie, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, and Xue-Jun Kong. 2022. "A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder" Cells 11, no. 1: 10. https://doi.org/10.3390/cells11010010

APA Style

Huang, J., Liu, J., Tian, R., Liu, K., Zhuang, P., Sherman, H. T., Budjan, C., Fong, M., Jeong, M.-S., & Kong, X.-J. (2022). A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells, 11(1), 10. https://doi.org/10.3390/cells11010010

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