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Disease-targeted sequencing: a cornerstone in the clinic

Nature Reviews Genetics volume 14, pages 295–300 (2013)Cite this article

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Abstract

With the declining cost of sequencing and the ongoing discovery of disease genes, it is now possible to examine hundreds of genes in a single disease-targeted test. Although exome- and genome-sequencing approaches are beginning to compete, disease-targeted testing retains certain advantages and still holds a firm place in the diagnostic evaluation. Here I examine the current state of clinical disease-targeted sequencing and evaluate the benefits and challenges of incorporating sequencing tests into patient care.

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Acknowledgements

This work was supported in part by US National Institutes of Health grants U41HG006834 and U01HG006500.

Author information

Authors and Affiliations

  1. Heidi L. Rehm is at the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA,

    Heidi L. Rehm

  2. and the Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, Massachusetts 02139, USA.,

    Heidi L. Rehm

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  1. Heidi L. Rehm
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Correspondence to Heidi L. Rehm.

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Competing interests

Heidi L. Rehm is employed in a not-for-profit, fee-for-service clinical laboratory of Partners Healthcare.

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PowerPoint slides

Glossary

Array-based oligo-hybridization sequencing

A method of DNA sequencing that uses array-conjugated oligonucleotide probes to determine the DNA sequence through differential hybridization of matched and mismatched probes at each base in a stretch of DNA.

Cardiomyopathy

A pathological state of the cardiac muscle that can result in increased muscle mass (that is, hypertrophic cardiomyopathy), enlargement of the cardiac chambers (that is, dilated cardiomyopathy) or fatty and fibrotic tissue replacement associated with decreased right ventricular wall movement and arrhythmia (that is, arrhythmogenic right ventricular cardiomyopathy).

Coverage

The quantity of DNA sequence reads that overlay a defined region of DNA sequence; higher coverage generally allows more accurate detection of sequence variants.

Cytogenomic arrays

Microarray technologies used to assess the entire nuclear genome for gains and losses of chromosome segments.

Fabry's disease

A rare genetic disorder primarily involving the heart, kidneys and neurosensory system that is caused by lysosomal storage dysfunction owing to the absence of functional α-galactosidase enzyme.

Lynch syndrome

A form of inherited cancer, traditionally referred to as hereditary nonpolyposis colon cancer, that leads to increased risk for tumours of the digestive track, particularly the colon.

Muscular dystrophy

A muscle disorder in which defects in muscle proteins lead to gradual weakening of muscle function owing to degeneration of muscle cells.

Otoacoustic emission testing

A test of hearing function that involves the analysis of minute sounds produced by cells in the cochlear hearing organ in response to a sound input.

Retinitis pigmentosa

A form of retinal degeneration in which inherited defects in the photoreceptor cells lead to gradual vision loss.

Sanger sequencing

A method developed by Frederick Sanger to determine the sequence of DNA through the random incorporation of labelled dideoxynucleotides that cause nucleotide-specific chain termination.

Temporal bone evaluation

The use of CT or MRI imaging to examine the bony structures surrounding the inner ear organ.

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Rehm, H. Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet 14, 295–300 (2013). https://doi.org/10.1038/nrg3463

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