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Series GSE81178 Query DataSets for GSE81178
Status Public on May 07, 2016
Title Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma
Organism Homo sapiens
Experiment type Other
Summary Background: Cell free DNA (cfDNA) in plasma has received increasing attention and has been studied in a broad range of clinical conditions implicating inflammation, cancer, and aging. However, few studies have focused on mitochondrial DNA (mtDNA) in the cell free form. This study characterized the size distribution and sequence characteristics of plasma cell free mtDNA (cf mtDNA) in humans.Methods and Results: We optimized DNA isolation and next-generation sequencing library preparation protocols to better retain short DNA fragments from plasma, and applied these optimized methods to plasma samples from patients with sepsis. After massive parallel sequencing, we verified that our methods can retain substantially shorter DNA fragments than the standard isolation method, resulting in an average of 11.5 fold increase in short DNA fragments yield (DNA < 100bp). We report that cf mtDNA in plasma is highly enriched in short-size cfDNA (30 ~ 60 bp), which is much shorter than the value previously reported (~140 bp). Motivated by this unique size distribution, we size-selected short cfDNA fragments from the sequencing library, which further increased the mtDNA recovery rate by an average of 10.4 fold. Using this approach we detected mixtures of different mtDNA sequences, termed heteroplasmy, in plasma from 3 patients. In one patient who previously received bone marrow transplantation, different minor allele frequencies were observed between plasma and white blood cells (WBC) at heteroplasmic mtDNA sites, consistent with mixed-tissue origin for plasma DNA.Conclusion: mtDNA in plasma exists as very short fragments that exhibit mtDNA heteroplasmy distribution differences from that found in a single organ/tissue. This study is the first report of genome wide identification of mtDNA heteroplasmy in human plasma. Our optimized method can be used to investigate the potential utility of cf mtDNA fragments and heteroplasmy as biomarkers in various diseases.
Overall design Examine plasma mtDNA of 7 individuals by 3 different protocols
Contributor(s) Zhang R, Nakahira K, Guo X, Choi A, Gu Z
Citation(s) 27811968
Submission date May 06, 2016
Last update date Sep 13, 2019
Contact name Ruoyu Zhang
Organization name Regeneron
Street address 777 Old Saw Mill River Road
City Tarrytown
ZIP/Postal code 10591
Country USA
Platforms (2)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (28)
GSM2144218 standard 1
GSM2144219 standard 2
GSM2144220 standard 17
BioProject PRJNA320827
SRA SRP074460

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Supplementary file Size Download File type/resource
GSE81178_heteroplasmy.txt.gz 582 b (ftp)(http) TXT
GSE81178_mtDNA_concentration.txt.gz 571 b (ftp)(http) TXT
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