NUMT Confounding Biases Mitochondrial Heteroplasmy Calls in Favor of the Reference Allele.

ABSTRACT: Homology between mitochondrial DNA (mtDNA) and nuclear DNA of mitochondrial origin (nuMTs) causes confounding when aligning short sequence reads to the reference human genome, as the true sequence origin cannot be determined. Using a systematic in silico approach, we here report the impact of all potential mitochondrial variants on alignment accuracy and variant calling. A total of 49,707 possible mutations were introduced across the 16,569 bp reference mitochondrial genome (16,569 × 3 alternative alleles), one variant at-at-time. The resulting in silico fragmentation and alignment to the entire reference genome (GRCh38) revealed preferential mapping of mutated mitochondrial fragments to nuclear loci, as variants increased loci similarity to nuMTs, for a total of 807, 362, an

SUBMITTER: Maude H 

PROVIDER: S-EPMC6773831 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature