Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 卢煜明教授 (化学病理学系) |
| 赵慧君教授 (化学病理学系) |
| 梁德杨教授 (妇产科学系) |
| 孙昊教授 (化学病理学系) |
| 廖嘉炜教授 (化学病理学系) |
| 江培勇教授 (化学病理学系) |
| 郑文莉博士 (化学病理学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1073/pnas.1406103111 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/52WOS source URL
其它资讯
摘要Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.
着者Yu SCY, Chan KCA, Zheng YWL, Jiang PY, Liao GJW, Sun H, Akolekar R, Leung TY, Go ATJI, van Vugt JMG, Minekawa R, Oudejans CBM, Nicolaides KH, Chiu RWK, Lo YMD
期刊名称PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版年份2014
月份6
日期10
卷号111
期次23
出版社NATL ACAD SCIENCES
页次8583 - 8588
国际标準期刊号0027-8424
语言英式英语
关键词Down syndrome; fetal aneuploidy; next-generation sequencing; size profiling; Turner syndrome
Web of Science 学科类别Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics
