Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans  

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

机构地区：[1]Vanderbilt Ingram Cancer Center,Center for Quantitative Sciences [2]Department of Applied Mathematics,Chiayi University (NCYU) [3]Institute of Cancer Epidemiology,Danish Cancer Society [4]Vanderbilt Epidemiology Center,Vanderbilt University School of Medicine [5]National Council on Radiation Protection & Measurements

出　　处：《Journal of Genetics and Genomics》2013年第12期607-615,共9页遗传学报（英文版）

基　　金：supported by the grant from the National Cancer Institute(RO1 CA104666);supported in part by the Vanderbilt-Ingram Cancer Center(P30 CA68485)

摘　　要：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%, cor- resnondin to abottleneck of about 200 mtDNA.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%, cor- resnondin to abottleneck of about 200 mtDNA.

关 键 词：Maternal inheritance Next-generation sequencing High-depth sequencing HETEROPLASMY mtDNA mutations BOTTLENECK 

分 类 号：R394[医药卫生—医学遗传学]