The Value of Whole‐Genome Sequencing for Mitochondrial DNA Population Studies: Strategies and Criteria for Extracting High‐Quality Mitogenome Haplotypes

Abstract

Whole‐genome sequencing (WGS) data present a readily available resource for mitochon-drial genome (mitogenome) haplotypes that can be utilized for genetics research including population studies. However, the reconstruction of the mitogenome is complicated by nuclear mitochon-drial DNA (mtDNA) segments (NUMTs) that co‐align with the mtDNA sequences and mimic authentic heteroplasmy. Two minimum variant detection thresholds, 5% and 10%, were assessed for the ability to produce authentic mitogenome haplotypes from a previously generated WGS dataset. Variants associated with NUMTs were detected in the mtDNA alignments for 91 of 917 (~8%) Swedish samples when the 5% frequency threshold was applied. The 413 observed NUMT variants were predominantly detected in two regions (nps 12,612–13,105 and 16,390–16,527), which were con-sistent with previously documented NUMTs. The number of NUMT variants was reduced by ~97% (400) using a 10% frequency threshold. Furthermore, the 5% frequency data were inconsistent with a platinum‐quality mitogenome dataset with respect to observed heteroplasmy. These analyses il-lustrate that a 10% variant detection threshold may be necessary to ensure the generation of reliable mitogenome haplotypes from WGS data resources.