2024
Quantifying constraint in the human mitochondrial genome
Lake N, Ma K, Liu W, Battle S, Laricchia K, Tiao G, Puiu D, Ng K, Cohen J, Compton A, Cowie S, Christodoulou J, Thorburn D, Zhao H, Arking D, Sunyaev S, Lek M. Quantifying constraint in the human mitochondrial genome. Nature 2024, 635: 390-397. PMID: 39415008, DOI: 10.1038/s41586-024-08048-x.Peer-Reviewed Original ResearchMitochondrial genomeDeleterious variationMtDNA mutator modelHuman mitochondrial genomeGenome Aggregation DatabaseMtDNA variationMtDNA variantsMitochondrial DNANoncoding regionsMitochondrial proteinsRRNA geneGenetic variationMtDNAThree-dimensional structureMutation modelPathogenic variationDisease relevanceAggregation DatabaseGenomeLarge-scale population datasetRRNAConstrained sitesGenesTRNAPopulation datasets
2023
Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality
Hong Y, Battle S, Shi W, Puiu D, Pillalamarri V, Xie J, Pankratz N, Lake N, Lek M, Rotter J, Rich S, Kooperberg C, Reiner A, Auer P, Heard-Costa N, Liu C, Lai M, Murabito J, Levy D, Grove M, Alonso A, Gibbs R, Dugan-Perez S, Gondek L, Guallar E, Arking D. Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality. Nature Communications 2023, 14: 6113. PMID: 37777527, PMCID: PMC10542802, DOI: 10.1038/s41467-023-41785-7.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsOwn circular genomeState of heteroplasmyAging-related diseasesNuclear genomeMitochondrial genomeCircular genomeMtDNA single nucleotide variantsMitochondrial DNASomatic cellsMitochondrial mutationsMtDNA heteroplasmyGenomeNucleotide variantsHeteroplasmyDNA moleculesFunctional roleMitochondriaUK BiobankCertain cancersVariantsDNAMutationsCopiesCells
2020
Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus
Frazier A, Compton A, Kishita Y, Hock D, Welch A, Amarasekera S, Rius R, Formosa L, Imai-Okazaki A, Francis D, Wang M, Lake N, Tregoning S, Jabbari J, Lucattini A, Nitta K, Ohtake A, Murayama K, Amor D, McGillivray G, Wong F, van der Knaap M, Vermeulen R, Wiltshire E, Fletcher J, Lewis B, Baynam G, Ellaway C, Balasubramaniam S, Bhattacharya K, Freckmann M, Arbuckle S, Rodriguez M, Taft R, Sadedin S, Cowley M, Minoche A, Calvo S, Mootha V, Ryan M, Okazaki Y, Stroud D, Simons C, Christodoulou J, Thorburn D. Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus. Med 2020, 2: 49-73.e10. PMID: 33575671, PMCID: PMC7875323, DOI: 10.1016/j.medj.2020.06.004.Peer-Reviewed Original ResearchConceptsMitochondrial diseasePediatric mitochondrial diseaseMitochondrial oxidative phosphorylation complexes IOxidative phosphorylation complexes IDominant-negative mannerStudy of RNADNA sequencing techniquesSegmental duplicationsGenomic strategiesQuantitative proteomicsWhole genomeGenomic investigationsGene locusRepetitive regionsSequencing techniquesGenomeComplex IRecessive deletionsLociWhole exomeDuplicationMonogenic diseasesDe novo duplicationExome sequencingPontocerebellar hypoplasia
2015
Leigh syndrome: One disorder, more than 75 monogenic causes
Lake N, Compton A, Rahman S, Thorburn D. Leigh syndrome: One disorder, more than 75 monogenic causes. Annals Of Neurology 2015, 79: 190-203. PMID: 26506407, DOI: 10.1002/ana.24551.Peer-Reviewed Original Research