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A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder
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 seque...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750892/ https://www.ncbi.nlm.nih.gov/pubmed/35011571 http://dx.doi.org/10.3390/cells11010010 |
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author | Huang, Jie Liu, Jun Tian, Ruiyi Liu, Kevin Zhuang, Patrick Sherman, Hannah Tayla Budjan, Christoph Fong, Michelle Jeong, Min-Seo Kong, Xue-Jun |
author_facet | Huang, Jie Liu, Jun Tian, Ruiyi Liu, Kevin Zhuang, Patrick Sherman, Hannah Tayla Budjan, Christoph Fong, Michelle Jeong, Min-Seo Kong, Xue-Jun |
author_sort | Huang, Jie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8750892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87508922022-01-12 A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder Huang, Jie Liu, Jun Tian, Ruiyi Liu, Kevin Zhuang, Patrick Sherman, Hannah Tayla Budjan, Christoph Fong, Michelle Jeong, Min-Seo Kong, Xue-Jun Cells Article 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. MDPI 2021-12-21 /pmc/articles/PMC8750892/ /pubmed/35011571 http://dx.doi.org/10.3390/cells11010010 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Huang, Jie Liu, Jun Tian, Ruiyi Liu, Kevin Zhuang, Patrick Sherman, Hannah Tayla Budjan, Christoph Fong, Michelle Jeong, Min-Seo Kong, Xue-Jun A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title | A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title_full | A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title_fullStr | A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title_full_unstemmed | A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title_short | A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder |
title_sort | next generation sequencing-based protocol for screening of variants of concern in autism spectrum disorder |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750892/ https://www.ncbi.nlm.nih.gov/pubmed/35011571 http://dx.doi.org/10.3390/cells11010010 |
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