Topologic Analysis of Plasma Mitochondrial DNA Reveals the Coexistence of Both Linear and Circular Molecules
Publication in refereed journal

替代計量分析
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其它資訊
摘要BACKGROUND
Cellular mitochondrial DNA (mtDNA) is organized as circular, covalently closed and double-stranded DNA. Studies have demonstrated the presence of short mtDNA fragments in plasma. It is not known whether circular mtDNA might concurrently exist with linear mtDNA in plasma.

METHODS
We elucidated the topology of plasma mtDNA using restriction enzyme BfaI cleavage signatures on mtDNA fragment ends to differentiate linear and circular mtDNA. mtDNA fragments with both ends carrying BfaI cleavage signatures were defined as circular-derived mtDNA, whereas those with no cleavage signature or with 1 cleavage signature were defined as linear-derived mtDNA. An independent assay using exonuclease V to remove linear DNA followed by restriction enzyme MspI digestion was used for confirming the conclusions based on BfaI cleavage analysis. We analyzed the presence of BfaI cleavage signatures on plasma DNA ends in nonhematopoietically and hematopoietically derived DNA molecules by sequencing plasma DNA of patients with liver transplantation and bone marrow transplantation.

RESULTS
Both linear and circular mtDNA coexisted in plasma. In patients with liver transplantation, donor-derived (i.e., liver) mtDNA molecules were mainly linear (median fraction, 91%; range, 75%–97%), whereas recipient-derived (i.e., hematopoietic) mtDNA molecules were mainly circular (median fraction, 88%; range, 77%–93%). The proportion of linear mtDNA was well correlated with liver DNA contribution in the plasma DNA pool (r = 0.83; P value = 0.0008). Consistent data were obtained from a bone marrow transplantation recipient in whom the donor-derived (i.e., hematopoietic) mtDNA molecules were predominantly circular.

CONCLUSIONS
Linear and circular mtDNA molecules coexist in plasma and may have different tissue origins.
著者Ma MJL, Zhang HA, Jiang PY, Sin STK, Lam WKJ, Cheng SH, Lee WS, Gai WX, Tse OYO, Peng WL, Wong J, Raghupathy R, Wong RSM, Sahota D, Leung TY, Chan KCA, Chiu RWK, Lo YMD
期刊名稱Clinical Chemistry
出版年份2019
月份9
卷號65
期次9
出版社AMER ASSOC CLINICAL CHEMISTRY
頁次1161 - 1170
國際標準期刊號0009-9147
語言英式英語
Web of Science 學科類別Medical Laboratory Technology;Medical Laboratory Technology

上次更新時間 2020-01-07 於 01:30