Related Experiment Video
Updated: Sep 21, 2025
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis
Ryan L Davis1, Kishore R Kumar1, Clare Puttick1
1From the Department of Neurogenetics (R.L.D., K.R.K., C.L., K.E.A., F.E.-H., J.-S.P., C.M.S.), Kolling Institute, Faculty of Medicine and Health, University of Sydney and Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards; Kinghorn Centre for Clinical Genomics (R.L.D., K.R.K., C.P., A.E.M., V.G., A.C.M., M.E.D., M.J.C., C.M.S.), Garvan Institute of Medical Research, Darlinghurst; Department of Neurology (K.R.K., C.L., K.E.A., F.E.-H., C.M.S.), Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards; Dr. Kumar is now with Molecular Medicine Laboratory, Concord Hospital, Concord, New South Wales, Australia; Dr. Park is now with Cenyx Biotech, Jongno-gu, Seoul, South Korea; Brain and Mitochondrial Research Group (J.C.), Murdoch Children's Research Institute, Parkville, Melbourne; Department of Paediatrics (J.C.), University of Melbourne, Victoria; Prof. Schofield is now with GenIMPACT: Centre for Economic Impacts of Genomic Medicine, Macquarie University, Macquarie Park; Prof. Dinger is now with School of Biotechnology and Biomolecular Sciences, University of New South Wales, Randwick; and Prof. Cowley is now with Computational Biology Group, Children's Cancer Institute, University of New South Wales, Randwick, Australia.
Background And Objectives:
Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, and causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive genetic diagnostic test would be highly useful and transform the field. We applied whole-genome sequencing (WGS) to evaluate the variant detection rate and diagnostic capacity of this technology with a view to simplifying and improving the MD diagnostic pathway.
Methods:
Adult patients presenting to a specialist MD clinic in Sydney, Australia, were recruited to the study if they satisfied clinical MD (Nijmegen) criteria. WGS was performed on blood DNA, followed by clinical genetic analysis for known pathogenic MD-associated variants and MD mimics.
Results:
Of the 242 consecutive patients recruited, 62 participants had "definite," 108 had "probable," and 72 had "possible" MD classification by the Nijmegen criteria. Disease-causing variants were identified for 130 participants, regardless of the location of the causative genetic variants, giving an overall diagnostic rate of 53.7% (130 of 242). Identification of causative genetic variants informed precise treatment, restored reproductive confidence, and optimized clinical management of MD.
Discussion:
Comprehensive bigenomic sequencing accurately detects causative genetic variants in affected MD patients, simplifying diagnosis, enabling early treatment, and informing the risk of genetic transmission.
Related Concept Videos
02:59Animal Mitochondrial Genetics
01:29Modern Molecular Taxonomy