LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias[S]

We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients wi...

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Bibliographic Details
Published in:Journal of lipid research 2014-04, Vol.55 (4), p.765-772
Main Authors: Johansen, Christopher T., Dubé, Joseph B., Loyzer, Melissa N., MacDonald, Austin, Carter, David E., McIntyre, Adam D., Cao, Henian, Wang, Jian, Robinson, John F., Hegele, Robert A.
Format: Article
Language:English
Subjects:
DNA diagnosis
DNA Mutational Analysis
Dyslipidemias - genetics
familial dyslipidemia
Genetic Predisposition to Disease
genetic risk score
High-Throughput Nucleotide Sequencing
Humans
Methods
Molecular Diagnostic Techniques
Molecular Sequence Annotation
Mutation
mutations
next generation sequencing
polygenic dyslipidemia
Sanger sequencing
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Summary:We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.D045963