RT Journal Article
SR Electronic
T1 A catalog of homoplasmic and heteroplasmic mitochondrial DNA variants in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 798264
DO 10.1101/798264
A1 Alexandre Bolze
A1 Fernando Mendez
A1 Simon White
A1 Francisco Tanudjaja
A1 Magnus Isaksson
A1 Ruomu Jiang
A1 Andrew Dei Rossi
A1 Elizabeth T. Cirulli
A1 Misha Rashkin
A1 William J. Metcalf
A1 Joseph J. Grzymski
A1 William Lee
A1 James T. Lu
A1 Nicole L. Washington
YR 2020
UL http://biorxiv.org/content/early/2020/06/26/798264.abstract
AB 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 StatementAB, FM, SW, FJ, MI, RJ, ADR, EC, MR, WL, JL and NW are employees of Helix.