@article{7d4ae0dca85049c2957409b289a24192,
title = "Comparison of whole genome sequencing and targeted sequencing for mitochondrial DNA",
abstract = "Mitochondrial dysfunction has emerged to be associated with a broad spectrum of diseases, and there is an increasing demand for accurate detection of mitochondrial DNA (mtDNA) variants. Whole genome sequencing (WGS) has been the dominant sequencing approach to identify genetic variants in recent decades, but most studies focus on variants on the nuclear genome. Whole genome sequencing is also costly and time consuming. Sequencing specifically targeted for mtDNA is commonly used in the diagnostic settings and has lower costs. However, there is a lack of pairwise comparisons between these two sequencing approaches for calling mtDNA variants on a population basis. In this study, we compared WGS and mtDNA-targeted sequencing (targeted-seq) in analyzing mitochondrial DNA from 1499 participants recruited into the Severe Asthma Research Program (SARP). Our study reveals that targeted-sequencing and WGS have comparable capacity to determine genotypes and to call haplogroups and homoplasmies on mtDNA. However, there exists a large variability in calling heteroplasmies, especially for low-frequency heteroplasmies, which indicates that investigators should be cautious about heteroplasmies acquired from different sequencing methods. Further research is highly desired to improve variant detection methods for mitochondrial DNA.",
keywords = "Asthma, Mitochondrial DNA, Targeted sequencing, Whole genome sequencing",
author = "{NHLBI Severe Asthma Research Program (SARP)} and Ruoying Chen and Aldred, {Micheala A.} and Weiling Xu and Joe Zein and Peter Bazeley and Comhair, {Suzy A.A.} and Meyers, {Deborah A.} and Bleecker, {Eugene R.} and Chunyu Liu and Erzurum, {Serpil C.} and Bo Hu",
note = "Funding Information: This work was supported by awards from the National Heart, Lung, and Blood Institute (HL081064, HL103453, and HL109250 to SCE, and R35HL140019 to MAA); this project was also supported in part by the National Center for Advancing Translational Sciences (ULTR000439). S.C. Erzurum is supported in part by the Alfred Lerner Chair for Biomedical Research. SARP was supported by awards from National Heart, Lung, and Blood Institute (U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109046, U10 HL109250, U10 HL109164, U10 HL109086). TOPMed WGS data was supported by the National Heart, Lung, and Blood Institute. Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonization, data management, sample-identity QC, and general program coordination were provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data. The authors would like to thank the editor and the reviewers for their insightful comments, which significantly improved the quality of this manuscript. Funding Information: SARP was supported by awards from National Heart, Lung, and Blood Institute (U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109046, U10 HL109250, U10 HL109164, U10 HL109086). TOPMed WGS data was supported by the National Heart, Lung, and Blood Institute. Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonization, data management, sample-identity QC, and general program coordination were provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data. Funding Information: This work was supported by awards from the National Heart, Lung, and Blood Institute (HL081064, HL103453, and HL109250 to SCE, and R35HL140019 to MAA); this project was also supported in part by the National Center for Advancing Translational Sciences (ULTR000439). S.C. Erzurum is supported in part by the Alfred Lerner Chair for Biomedical Research. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V. and Mitochondria Research Society",
year = "2021",
month = may,
doi = "10.1016/j.mito.2021.01.006",
language = "English (US)",
volume = "58",
pages = "303--310",
journal = "Mitochondrion",
issn = "1567-7249",
publisher = "Elsevier",
}