ID

45292

Description

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 MeSH: Mitochondrial Diseases,Mitochondrial Disorders,Mitochondrial Disorder,Oxidative Phosphorylation Deficiencies,Oxidative Phosphorylation Deficiency,Respiratory Chain Deficiencies, Mitochondrial,Respiratory Chain Deficiency,Mitochondrial Respiratory Chain Deficiencies,Electron Transport Chain Deficiencies, Mitochondrial,Mitochondrial Electron Transport Chain Deficiencies https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000339 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.

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dbGaP study = phs000339

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1. 10/15/22 10/15/22 - Adrian Schulz

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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

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October 15, 2022

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