Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction.
Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction.
复制标题
DOI：
10.1016/j.ajhg.2020.09.006
复制
发表时间：
2020-11-05
影响因子：
9.8
通讯作者：
Lo YMD
中科院分区：
文献类型：
--
作者：
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;Reizis B;Lo YMD
血浆DNA片段组学是无细胞DNA诊断和研究的一个新兴领域。在小鼠模型中，已经显示细胞外DNA酶，DNASE1L3，在血浆DNA的片段化中起作用。在人类中，DNASE1L3缺陷导致家族性单基因系统性红斑狼疮，具有儿童期发病和抗dsDNA反应性。在这项研究中，我们发现，与DNASE1L3疾病相关的基因变异的人类患者表现出的大小和血浆DNA的“CC”末端基序的减少畸变。此外，我们证明，从DNASE1L3消化细胞核的DNA显示出153 bp的中位长度与CC基序频率类似的健康个体的血浆DNA。腺相关病毒为基础的转导Dnase1l3到Dnase1l3缺陷小鼠恢复了野生型小鼠的血浆DNA中所看到的结束基序配置文件。我们的研究结果表明，DNASE1L3是一个重要的球员在血浆DNA片段，这似乎是在一个细胞外的方式来调节血浆DNA的大小和基序频率。
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.
登录
查看更多内容
影响因子：
4
作者：
Lisowski, Leszek;Tay, Szun Szun;Alexander, Ian Edward
通讯作者：
Alexander, Ian Edward
影响因子：
2.6
作者：
Carbonella, A.;Mancano, G.;Ferraccioli, G.
通讯作者：
Ferraccioli, G.
DOI：
10.1073/pnas.1500076112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Jiang, Peiyong;Chan, Carol W. M.;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
通过碎片尺寸分析增强了循环肿瘤DNA的检测。
影响因子：
17.1
作者：
Mouliere F;Chandrananda D;Piskorz AM;Moore EK;Morris J;Ahlborn LB;Mair R;Goranova T;Marass F;Heider K;Wan JCM;Supernat A;Hudecova I;Gounaris I;Ros S;Jimenez-Linan M;Garcia-Corbacho J;Patel K;Østrup O;Murphy S;Eldridge MD;Gale D;Stewart GD;Burge J;Cooper WN;van der Heijden MS;Massie CE;Watts C;Corrie P;Pacey S;Brindle KM;Baird RD;Mau-Sørensen M;Parkinson CA;Smith CG;Brenton JD;Rosenfeld N
通讯作者：
Rosenfeld N
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y