Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort

F.C. Garton, B. Benyamin, Q. Zhao, Z. Liu, J. Gratten, A.K. Henders, Z.-H. Zhang, J. Edson, S. Furlong, S. Morgan, S. Heggie, K. Thorpe, C. Pfluger, K.A. Mather, P.S. Sachdev, A.F. McRae, M.R. Robinson, S. Shah, P.M. Visscher, M. Mangelsdorf, R.D. Henderson, N.R. Wray, P.A. McCombe, Molecular Genetics & Genomic Medicine 5 (2017) 418–428.


Journal Article | Published | English
Author
Garton, Fleur C.; Benyamin, Beben; Zhao, Qiongyi; Liu, Zhijun; Gratten, Jacob; Henders, Anjali K.; Zhang, Zong-Hong; Edson, Janette; Furlong, Sarah; Morgan, Sarah; Heggie, Susan; Thorpe, Kathryn
All
Abstract
Sections PDFPDF Tools Share Abstract Background: Gene discovery has provided remarkable biological insights into amyotrophic lateral sclerosis (ALS). One challenge for clinical application of genetic testing is critical evaluation of the significance of reported variants. Methods: We use whole exome sequencing (WES) to develop a clinically relevant approach to identify a subset of ALS patients harboring likely pathogenic mutations. In parallel, we assess if DNA methylation can be used to screen for pathogenicity of novel variants since a methylation signature has been shown to associate with the pathogenic C9orf72 expansion, but has not been explored for other ALS mutations. Australian patients identified with ALS‐relevant variants were cross‐checked with population databases and case reports to critically assess whether they were “likely causal,” “uncertain significance,” or “unlikely causal.” Results: Published ALS variants were identified in >10% of patients; however, in only 3% of patients (4/120) could these be confidently considered pathogenic (in SOD1 and TARDBP). We found no evidence for a differential DNA methylation signature in these mutation carriers. Conclusions: The use of WES in a typical ALS clinic demonstrates a critical approach to variant assessment with the capability to combine cohorts to enhance the largely unknown genetic basis of ALS.
Publishing Year
Date Published
2017-07-01
Journal Title
Molecular Genetics & Genomic Medicine
Volume
5
Issue
4
Page
418-428
ISSN
IST-REx-ID

Cite this

Garton FC, Benyamin B, Zhao Q, et al. Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort. Molecular Genetics & Genomic Medicine. 2017;5(4):418-428. doi:10.1002/mgg3.302
Garton, F. C., Benyamin, B., Zhao, Q., Liu, Z., Gratten, J., Henders, A. K., … McCombe, P. A. (2017). Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort. Molecular Genetics & Genomic Medicine. Wiley. https://doi.org/10.1002/mgg3.302
Garton, Fleur C., Beben Benyamin, Qiongyi Zhao, Zhijun Liu, Jacob Gratten, Anjali K. Henders, Zong-Hong Zhang, et al. “Whole Exome Sequencing and DNA Methylation Analysis in a Clinical Amyotrophic Lateral Sclerosis Cohort.” Molecular Genetics & Genomic Medicine. Wiley, 2017. https://doi.org/10.1002/mgg3.302.
F. C. Garton et al., “Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort,” Molecular Genetics & Genomic Medicine, vol. 5, no. 4. Wiley, pp. 418–428, 2017.
Garton FC, Benyamin B, Zhao Q, Liu Z, Gratten J, Henders AK, Zhang Z-H, Edson J, Furlong S, Morgan S, Heggie S, Thorpe K, Pfluger C, Mather KA, Sachdev PS, McRae AF, Robinson MR, Shah S, Visscher PM, Mangelsdorf M, Henderson RD, Wray NR, McCombe PA. 2017. Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort. Molecular Genetics & Genomic Medicine. 5(4), 418–428.
Garton, Fleur C., et al. “Whole Exome Sequencing and DNA Methylation Analysis in a Clinical Amyotrophic Lateral Sclerosis Cohort.” Molecular Genetics & Genomic Medicine, vol. 5, no. 4, Wiley, 2017, pp. 418–28, doi:10.1002/mgg3.302.
All files available under the following license(s):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]

Link(s) to Main File(s)
Access Level
OA Open Access

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar