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Nonhematopoietically Derived DNA Is Shorter than Hematopoietically Derived DNA in Plasma: A Transplantation Model

2011; American Association for Clinical Chemistry; Volume: 58; Issue: 3 Linguagem: Inglês

10.1373/clinchem.2011.169318

1530-8561

Yama W. L. Zheng, Kelvin Chan, Hao Sun, Peiyong Jiang, Xiaoxi Su, Eric Z. Chen, Fiona M. F. Lun, Emily C W Hung, Vincent Lee, John Wong, Paul B.S. Lai, Chi Kong Li, Rossa W. K. Chiu, Y. M. Dennis Lo,

Renal Transplantation Outcomes and Treatments

Abstract BACKGROUND Plasma DNA is predominantly hematopoietic in origin. The size difference between maternal- and fetal-derived DNA in maternal plasma prompted us to investigate whether there was any discrepancy in molecular size between hematopoietically and nonhematopoietically derived DNA in plasma. METHODS Plasma DNA samples from 6 hematopoietic stem cell transplant recipients and 1 liver transplant recipient were analyzed by massively parallel paired-end sequencing. The size of each fragment was deduced from the alignment positions of the paired reads. In sex-mismatched transplant recipients, the reads from chromosome Y were used as markers for the male donor/recipient. For other transplant recipients, the reads of the donor- and recipient-specific alleles were identified from the single-nucleotide polymorphism genotypes. RESULTS In male patients receiving female hematopoietic stem cells, more chromosome Y–derived DNA molecules (nonhematopoietically derived) were ≤150 bp than the autosome-derived ones (mainly hematopoietically derived) (median difference, 9.9%). In other hematopoietic stem cell transplant recipients, more recipient-specific DNA molecules (nonhematopoietically derived) were ≤150 bp than the donor-specific ones (hematopoietically derived) (median difference, 14.8%). In the liver transplant recipient, more donor-derived DNA molecules (liver derived) were ≤150 bp than the recipient-derived ones (mainly hematopoietically derived) (difference, 13.4%). The nonhematopoietically derived DNA exhibited a reduction in a 166-bp peak compared with the hematopoietically derived DNA. A 10-bp periodicity in size distribution below approximately 143 bp was observed in both DNA populations. CONCLUSIONS Massively parallel sequencing is a powerful tool for studying posttransplantation chimerism. Plasma DNA molecules exhibit a distinct fragmentation pattern, with the nonhematopoietically derived molecules being shorter than the hematopoietically derived ones.