Mitochondrial DNA variation across 56,434 individuals in gnomAD.

ABSTRACT: Genomic databases of allele frequency are extremely helpful for evaluating clinical variants of unknown significance; however, until now, databases such as the Genome Aggregation Database (gnomAD) have focused on nuclear DNA and have ignored the mitochondrial genome (mtDNA). Here, we present a pipeline to call mtDNA variants that addresses three technical challenges: (1) detecting homoplasmic and heteroplasmic variants, present, respectively, in all or a fraction of mtDNA molecules; (2) circular mtDNA genome; and (3) misalignment of nuclear sequences of mitochondrial origin (NUMTs). We observed that mtDNA copy number per cell varied across gnomAD cohorts and influenced the fraction of NUMT-derived false-positive variant calls, which can account for the majority of putative heteroplasmies.

SUBMITTER: Laricchia KM 

PROVIDER: S-EPMC8896463 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature