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
2022
Mitochondrial DNA variation across 56,434 individuals in gnomAD
Laricchia KM, Lake NJ, Watts NA, Shand M, Haessly A, Gauthier L, Benjamin D, Banks E, Soto J, Garimella K, Emery J, Consortium G, Rehm HL, MacArthur DG, Tiao G, Lek M, Mootha VK, Calvo SE. Mitochondrial DNA variation across 56,434 individuals in gnomAD. Genome Research 2022, 32: gr.276013.121. PMID: 35074858, PMCID: PMC8896463, DOI: 10.1101/gr.276013.121.Peer-Reviewed Original ResearchConceptsMtDNA variantsMitochondrial DNA variationPathogenic mtDNA variantsWhole genome sequencesUnique mtDNA variantsGenome Aggregation DatabasePopulation allele frequenciesAllele frequenciesMtDNA copy numberMitochondrial genomeNuclear sequencesVariant callsDNA variationIndividuals of EuropeanMtDNA genomeAncestral populationsMtDNA moleculesGenomic databasesHeteroplasmic variantsNuclear DNAHomoplasmic variantsMitochondrial originFalse positive variant callsMtDNA copiesMitochondrial haplogroups