Clinical Bioinformatics in Precise Diagnosis of Mitochondrial Disease

Lishuang Shen; Elizabeth M McCormick; Colleen Clarke Muraresku; Marni J Falk; Xiaowu Gai

doi:10.1016/j.cll.2020.02.002

Clinical Bioinformatics in Precise Diagnosis of Mitochondrial Disease

Clin Lab Med. 2020 Jun;40(2):149-161. doi: 10.1016/j.cll.2020.02.002.

Authors

Lishuang Shen¹, Elizabeth M McCormick², Colleen Clarke Muraresku², Marni J Falk³, Xiaowu Gai⁴

Affiliations

¹ Keck School of Medicine of USC, Center for Personalized Medicine, Children's Hospital Los Angeles, Suite 300, 2100 West 3rd Street, Los Angeles, CA 90057, USA.
² Mitochondrial Medicine Frontier Program, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA.
³ CHOP Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, The Children's Hospital of Philadelphia, ARC 1002c, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
⁴ Keck School of Medicine of USC, Center for Personalized Medicine, Children's Hospital Los Angeles, Suite 300, 2100 West 3rd Street, Los Angeles, CA 90057, USA. Electronic address: xgai@chla.usc.edu.

Abstract

Clinical bioinformatics system is well-established for diagnosing genetic disease based on next-generation sequencing, but requires special considerations when being adapted for the next-generation sequencing-based genetic diagnosis of mitochondrial diseases. Challenges are caused by the involvement of mitochondrial DNA genome in disease etiology. Heteroplasmy and haplogroup are key factors in interpreting mitochondrial DNA variant effects. Data resources and tools for analyzing variant and sequencing data are available at MSeqDR, MitoMap, and HmtDB. Revised specifications of the American College of Medical Genetics/Association of Molecular Pathology standards and guidelines for mitochondrial DNA variant interpretation are proposed by the MSeqDr Consortium and community experts.

Keywords: Bioinformatics; Clinical sequencing; Mitochondrial disease; Pathogenicity; Phenotype; Variant annotation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Computational Biology*
Genome, Mitochondrial / genetics
High-Throughput Nucleotide Sequencing
Humans
Mitochondrial Diseases* / diagnosis
Mitochondrial Diseases* / genetics
Molecular Diagnostic Techniques*
Pathology, Molecular
Sequence Analysis, DNA*

Abstract

Publication types

MeSH terms

Grants and funding