Summary
High quality population allele frequencies of DNA variants can be used to discover new biology, and study rare disorders. Here, we created a public catalog of mitochondrial DNA variants based on a population of 195,983 individuals. We focused on 3 criteria: (i) the population is not enriched for mitochondrial disorders, or other clinical phenotypes, (ii) all genomes are sequenced and analyzed in the same clinical laboratory, and (iii) both homoplasmic and heteroplasmic variants are reported. We found that 47% of the mitochondrial genome was invariant in this population, including large stretches in the 2 rRNA genes. This information could be used to annotate the mitochondrial genome in future studies. We also showed how to use this resource for the interpretation of pathogenic variants for rare mitochondrial disorders. For example, 42% of variants previously reported to be pathogenic for Leber Hereditary Optic Neuropathy (LHON) should be reclassified.
Competing Interest Statement
AB, FM, SW, FJ, MI, RJ, ADR, EC, MR, WL, JL and NW are employees of Helix.
Footnotes
We added more stringent QC threshold for very low levels of contamination. These low levels of contamination were undetectable in the nuclear genome, but could have a small impact on heteroplasmic variants with low levels of heteroplasmy. This resulted in the removal of a couple hundreds samples and a few variants from the database. We provided an updated link to the database and have redone all of the analyses with the new samples and variants. We also added Figure 1 to better characterize the population. Figure 5 is also new.
https://s3.amazonaws.com/helix-research-public/mito/HelixMTdb_20200327.tsv
