title: Very low-level heteroplasmy mtDNA variations are inherited in humans.
abstract: Little is known about the inheritance of very low heteroplasmy mitochondria DNA (mtDNA) variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, corresponding to a bottleneck of about 200 mtDNA.
authors.affiliation: Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA. Electronic address: yan.guo@vanderbilt.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Applied Mathematics, Chiayi University (NCYU), Chiayi 60004, Taiwan, China.
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Li
authors.affiliation: Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA.
authors.forename: Quanhu
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen DK-2100, Denmark.
authors.forename: Jeanette F
authors.initials: JF
authors.lastname: Winther
authors.affiliation: Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: National Council on Radiation Protection & Measurements, Bethesda, MD 20814, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.affiliation: Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA. Electronic address: yu.shyr@vanderbilt.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
mesh_terms: D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D009035:Mothers; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial
keywords: Bottleneck; Heteroplasmy; High-depth sequencing; Maternal inheritance; Next-generation sequencing; mtDNA mutations