title: LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias.
abstract: 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.
authors: Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada N6A 5B7.
authors: Christopher T
authors: CT
authors: Johansen
authors: Joseph B
authors: JB
authors: Dubé
authors: Melissa N
authors: MN
authors: Loyzer
authors: Austin
authors: A
authors: MacDonald
authors: David E
authors: DE
authors: Carter
authors: Adam D
authors: AD
authors: McIntyre
authors: Henian
authors: H
authors: Cao
authors: Jian
authors: J
authors: Wang
authors: John F
authors: JF
authors: Robinson
authors: Robert A
authors: RA
authors: Hegele
mesh_terms: D004252:DNA Mutational Analysis; D050171:Dyslipidemias / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D025202:Molecular Diagnostic Techniques; D058977:Molecular Sequence Annotation; D009154:Mutation
keywords: DNA diagnosis; Sanger sequencing; familial dyslipidemia; genetic risk score; mutations; next generation sequencing; polygenic dyslipidemia