Neurology Individualized Medicine: When to Use Next-Generation Sequencing Panels

Christopher J. Klein, Tatiana Foroud

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Next-generation sequencing (NGS) is increasingly being applied to clinical testing. This practice is predicted to grow especially in neurology clinics because many of their patients have monogenetic causes for their “diagnostic odyssey.” The cost of sequencing has been steadily decreasing, but the cost of DNA sequencing is a minor part of the total cost. Downstream data analysis, storage, and interpretation account for most of the total expense. In patients with nonspecific neurologic disorders in which an extensive number of genetic differential diagnoses exist, whole-genome sequencing (WGS) or whole-exome sequencing (WES) has shown promise in the identification of genetic causes. However, both WGS and WES have incomplete coverage and produce a large number of rare variants of unknown importance. In addition, ethical dilemmas are often created by unexpected findings in genes unrelated to the initial sequencing indication. Targeted-panel NGS starts with the capture of a set of disease-focused genes, followed by massive parallel sequencing. For many genetically heterogeneous neurologic disorders, a genetic panel that is disease focused yet inclusive of a large genetic differential diagnosis can be defined to reduce cost, increase turnaround time, and optimize performance. Targeted-panel NGS is currently the preferred first-tier approach because it provides a reliable clinical application while eliminating unexpected ethical dilemmas. Targeted-panel NGS is leading to a paradigm shift in the diagnosis of many neurologic disorders, enabling individualized precision medicine. In this review, we provide an overview of WGS, WES, and targeted-panel NGS in consideration of their utility in clinical testing for neurologic diseases.

Original languageEnglish (US)
Pages (from-to)292-305
Number of pages14
JournalMayo Clinic Proceedings
Volume92
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Precision Medicine
Neurology
Exome
Nervous System Diseases
Costs and Cost Analysis
Genome
Differential Diagnosis
Information Storage and Retrieval
DNA Sequence Analysis
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neurology Individualized Medicine : When to Use Next-Generation Sequencing Panels. / Klein, Christopher J.; Foroud, Tatiana.

In: Mayo Clinic Proceedings, Vol. 92, No. 2, 01.02.2017, p. 292-305.

Research output: Contribution to journalReview article

@article{2be5e6822622418daba42eec3f43f54d,
title = "Neurology Individualized Medicine: When to Use Next-Generation Sequencing Panels",
abstract = "Next-generation sequencing (NGS) is increasingly being applied to clinical testing. This practice is predicted to grow especially in neurology clinics because many of their patients have monogenetic causes for their “diagnostic odyssey.” The cost of sequencing has been steadily decreasing, but the cost of DNA sequencing is a minor part of the total cost. Downstream data analysis, storage, and interpretation account for most of the total expense. In patients with nonspecific neurologic disorders in which an extensive number of genetic differential diagnoses exist, whole-genome sequencing (WGS) or whole-exome sequencing (WES) has shown promise in the identification of genetic causes. However, both WGS and WES have incomplete coverage and produce a large number of rare variants of unknown importance. In addition, ethical dilemmas are often created by unexpected findings in genes unrelated to the initial sequencing indication. Targeted-panel NGS starts with the capture of a set of disease-focused genes, followed by massive parallel sequencing. For many genetically heterogeneous neurologic disorders, a genetic panel that is disease focused yet inclusive of a large genetic differential diagnosis can be defined to reduce cost, increase turnaround time, and optimize performance. Targeted-panel NGS is currently the preferred first-tier approach because it provides a reliable clinical application while eliminating unexpected ethical dilemmas. Targeted-panel NGS is leading to a paradigm shift in the diagnosis of many neurologic disorders, enabling individualized precision medicine. In this review, we provide an overview of WGS, WES, and targeted-panel NGS in consideration of their utility in clinical testing for neurologic diseases.",
author = "Klein, {Christopher J.} and Tatiana Foroud",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.mayocp.2016.09.008",
language = "English (US)",
volume = "92",
pages = "292--305",
journal = "Mayo Clinic Proceedings",
issn = "0025-6196",
publisher = "Elsevier Science",
number = "2",

}

TY - JOUR

T1 - Neurology Individualized Medicine

T2 - When to Use Next-Generation Sequencing Panels

AU - Klein, Christopher J.

AU - Foroud, Tatiana

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Next-generation sequencing (NGS) is increasingly being applied to clinical testing. This practice is predicted to grow especially in neurology clinics because many of their patients have monogenetic causes for their “diagnostic odyssey.” The cost of sequencing has been steadily decreasing, but the cost of DNA sequencing is a minor part of the total cost. Downstream data analysis, storage, and interpretation account for most of the total expense. In patients with nonspecific neurologic disorders in which an extensive number of genetic differential diagnoses exist, whole-genome sequencing (WGS) or whole-exome sequencing (WES) has shown promise in the identification of genetic causes. However, both WGS and WES have incomplete coverage and produce a large number of rare variants of unknown importance. In addition, ethical dilemmas are often created by unexpected findings in genes unrelated to the initial sequencing indication. Targeted-panel NGS starts with the capture of a set of disease-focused genes, followed by massive parallel sequencing. For many genetically heterogeneous neurologic disorders, a genetic panel that is disease focused yet inclusive of a large genetic differential diagnosis can be defined to reduce cost, increase turnaround time, and optimize performance. Targeted-panel NGS is currently the preferred first-tier approach because it provides a reliable clinical application while eliminating unexpected ethical dilemmas. Targeted-panel NGS is leading to a paradigm shift in the diagnosis of many neurologic disorders, enabling individualized precision medicine. In this review, we provide an overview of WGS, WES, and targeted-panel NGS in consideration of their utility in clinical testing for neurologic diseases.

AB - Next-generation sequencing (NGS) is increasingly being applied to clinical testing. This practice is predicted to grow especially in neurology clinics because many of their patients have monogenetic causes for their “diagnostic odyssey.” The cost of sequencing has been steadily decreasing, but the cost of DNA sequencing is a minor part of the total cost. Downstream data analysis, storage, and interpretation account for most of the total expense. In patients with nonspecific neurologic disorders in which an extensive number of genetic differential diagnoses exist, whole-genome sequencing (WGS) or whole-exome sequencing (WES) has shown promise in the identification of genetic causes. However, both WGS and WES have incomplete coverage and produce a large number of rare variants of unknown importance. In addition, ethical dilemmas are often created by unexpected findings in genes unrelated to the initial sequencing indication. Targeted-panel NGS starts with the capture of a set of disease-focused genes, followed by massive parallel sequencing. For many genetically heterogeneous neurologic disorders, a genetic panel that is disease focused yet inclusive of a large genetic differential diagnosis can be defined to reduce cost, increase turnaround time, and optimize performance. Targeted-panel NGS is currently the preferred first-tier approach because it provides a reliable clinical application while eliminating unexpected ethical dilemmas. Targeted-panel NGS is leading to a paradigm shift in the diagnosis of many neurologic disorders, enabling individualized precision medicine. In this review, we provide an overview of WGS, WES, and targeted-panel NGS in consideration of their utility in clinical testing for neurologic diseases.

UR - http://www.scopus.com/inward/record.url?scp=85011700216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011700216&partnerID=8YFLogxK

U2 - 10.1016/j.mayocp.2016.09.008

DO - 10.1016/j.mayocp.2016.09.008

M3 - Review article

C2 - 28160876

AN - SCOPUS:85011700216

VL - 92

SP - 292

EP - 305

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

SN - 0025-6196

IS - 2

ER -