Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans

Yan Guo; Chung-I Li; Quanhu Sheng; Jeanette F. Winther; Qiuyin Cai; John D. Boice; Yu Shyr

doi:10.1016/j.jgg.2013.10.003

Volume 40 Issue 12

Dec. 2013

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Article Navigation > Journal of Genetics and Genomics > 2013 > 40(12): 607-615

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Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans

doi: 10.1016/j.jgg.2013.10.003

a
Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA
b
Department of Applied Mathematics, Chiayi University (NCYU), Chiayi 60004, Taiwan, China
c
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen DK-2100, Denmark
d
Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
e
National Council on Radiation Protection & Measurements, Bethesda, MD 20814, USA

More Information

Corresponding author: E-mail address: yan.guo@vanderbilt.edu (Yan Guo); E-mail address: yu.shyr@vanderbilt.edu (Yu Shyr)
Received Date: 2013-06-22
Accepted Date: 2013-10-27
Rev Recd Date: 2013-10-24

Available Online: 2013-12-08

Publish Date: 2013-12-20

Abstract

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.
- Maternal inheritance,
- Next-generation sequencing,
- High-depth sequencing,
- Heteroplasmy,
- mtDNA mutations,
- Bottleneck

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References(41)

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