title: Challenges of bringing next generation sequencing technologies to clinical molecular diagnostic laboratories.
abstract: Molecular diagnosis of complex dual genome mitochondrial disorders is a challenge. It requires the identification of deleterious mutations in one of the ~1,500 nuclear genes and the mitochondrial genome. If the molecular defect is in the mitochondrial genome, quantification of degree of mutation load (heteroplasmy) in affected tissues is important. Due to the extreme clinical and genetic heterogeneity, conventional sequence analysis of the candidate genes one-by-one is impractical, if not impossible. The newly developed massively parallel next generation sequencing (NGS) technique, that allows simultaneous sequence analysis of multiple target genes, when appropriately validated with deep coverage and proper quality controls, can be used as an effective comprehensive diagnostic approach in CLIA certified clinical laboratories.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX 77030, USA. ljwong@bcm.edu
authors.forename: Lee-Jun C
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics; D014644:Genetic Variation; D016678:Genome / Q000235:genetics; D054629:Genome, Mitochondrial; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics; D025202:Molecular Diagnostic Techniques / Q000379:methods* / Q000639:trends; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000639:trends
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial