Principles and clinical applications of next-generation DNA sequencing
- Peter J Hulick, MD, MMSc, FACMG
Peter J Hulick, MD, MMSc, FACMG
- Medical Director, Center for Medical Genetics
- NorthShore University HealthSystem
- Clinical Assistant Professor, University of Chicago, Pritzker School of Medicine
Technologies for sequencing DNA have improved dramatically, to the point that it has become practical to sequence an individual’s entire genome. Next-generation sequencing (NGS) is a type of DNA sequencing technology that uses parallel sequencing of multiple small fragments of DNA to determine sequence. This "high-throughput" technology has allowed a dramatic increase in the speed (and a decrease in the cost) at which an individual's genome can be sequenced.
The ability to sequence an entire genome raises several challenging questions for the clinician, including the following:
●When should NGS be considered clinically?
●What is the best choice among several types of genetic testing available?
●What is the clinical significance of findings from sequencing of an entire genome?
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- TERMINOLOGY AND EVOLUTION OF TECHNOLOGIES
- TECHNICAL CONSIDERATIONS
- Source of DNA
- Whole genome, exome, or gene panel
- Mutation databases
- CLINICAL USE OF NEXT-GENERATION SEQUENCING
- Indications for NGS
- - Diagnosis of complex diseases
- - Diagnosis of infections
- - Healthy people
- - Research
- Genetic discrimination
- Disclosure of findings from genome sequencing
- PRACTICAL ISSUES
- Where to order
- Cost and turnaround time
- Insurance reimbursement