Abstract:
:Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset and anti-dsDNA reactivity. In this study, we found that human patients with DNASE1L3 disease-associated gene variations showed aberrations in size and a reduction of a "CC" end motif of plasma DNA. Furthermore, we demonstrated that DNA from DNASE1L3-digested cell nuclei showed a median length of 153 bp with CC motif frequencies resembling plasma DNA from healthy individuals. Adeno-associated virus-based transduction of Dnase1l3 into Dnase1l3-deficient mice restored the end motif profiles to those seen in the plasma DNA of wild-type mice. Our findings demonstrate that DNASE1L3 is an important player in the fragmentation of plasma DNA, which appears to act in a cell-extrinsic manner to regulate plasma DNA size and motif frequency.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Chan RWY,Serpas L,Ni M,Volpi S,Hiraki LT,Tam LS,Rashidfarrokhi A,Wong PCH,Tam LHP,Wang Y,Jiang P,Cheng ASH,Peng W,Han DSC,Tse PPP,Lau PK,Lee WS,Magnasco A,Buti E,Sisirak V,AlMutairi N,Chan KCA,Chiu RWK,Reizidoi
10.1016/j.ajhg.2020.09.006subject
Has Abstractpub_date
2020-11-05 00:00:00pages
882-894issue
5eissn
0002-9297issn
1537-6605pii
S0002-9297(20)30326-8journal_volume
107pub_type
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