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Study Description

Human disorders of mitochondrial oxidative phosphorylation (OXPHOS) represent a devastating collection of inherited diseases. These disorders impact at least 1:5000 live births, and are characterized by multi-organ system involvement. They are characterized by remarkable locus heterogeneity, with mutations in the mtDNA as well as in over 77 nuclear genes identified to date. It is estimated that additional genes may be mutated in these disorders.

To discover the genetic causes of mitochondrial OXPHOS diseases, we performed targeted, deep sequencing of the entire mitochondrial genome (mtDNA) and the coding exons of over 1000 nuclear genes encoding the mitochondrial proteome. We applied this 'MitoExome' sequencing to 124 unrelated patients with a wide range of OXPHOS disease presentations from the Massachusetts General Hospital Mitochondrial Disorders Clinic.

The 2.3Mb targeted region was captured by hybrid selection and Illumina sequenced with paired 76bp reads. The total set of 1605 targeted nuclear genes included 1013 genes with strong evidence of mitochondrial localization from the MitoCarta database, 377 genes with weaker evidence of mitochondrial localization from the MitoP2 database and other sources, and 215 genes known to cause other inborn errors of metabolism. Approximately 88% of targeted bases were well-covered (>20X), with mean 200X coverage per targeted base.

  • Study Type: Case Set
  • Number of study subjects that have individual level data available through Authorized Access: 134

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Inclusion criteria diagnosis of mitochondrial disease based on the Morava or Bernier criteria.

Exclusion criteria: None.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Targeted Sequencing Illumina Genome Analyzer IIX N/A N/A
Targeted Region Sequencing Illumina HiSeq 2000 N/A N/A
Study History

Version 2 of the dbGaP posted study includes additional phenotype data, including information about clinical phenotypes observed among participants that is available to authorized users.

Selected publications
Diseases Related to Study (MESH terms)
Links to Other NCBI Resources
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Vamsi Mootha, MD. Department of Systems Biology, Harvard Medical School; Department of Medicine, Massachusetts General Hospital; Broad Institute of MIT and Havard, Boston, MA, USA
  • Institute
    • Massachusetts General Hospital, Boston, MA, USA
  • Funding Source
    • 1RC2HG005556-01. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA