Segmental duplication as potential biomarkers for non-invasive prenatal testing of aneuploidies

EBioMedicine

Zhi-Liang Ji¹  Yinghua Liu²  Ting Wang²  Yifan Li³  Qingge Li⁴  Xinwen Chen⁴  Ying Liu⁴  Qiuying Huang⁴  Xudong Wang⁴  Xingming Lin⁴  Yafang Wang⁴  Qiushun He⁴ 

[1]Corresponding authors.

[2]Centre for Reproduction and Genetics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu 215002, China

[3]National Institute for Data Science in Health and Medicine, School of Informatics, Xiamen University, Xiamen, Fujian 361102, China

[4]State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, State Key Laboratory of Cellular Stress Biology, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China

关键词: Segmental duplications;    Computational program;    Chromosome aneuploidy;    Digital PCR;    Prenatal diagnosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Segmental duplication (SD) regions are distinct targets for aneuploidy detection owing to the virtual elimination of amplification bias. The difficulty of searching SD sequences for assay design has hampered their applications. Methods: We developed a computational program, ChAPDes, which integrates SD searching, refinement, and design of specific PCR primer/probe sets in a pipeline to remove most of the manual work. The generated primer/probe sets were first tested in a multiplex multicolour melting curve analysis for the detection of five common aneuploidies. The primer/probe sets were then tested in a digital PCR assay for the detection of trisomy 21. Finally, a digital PCR protocol was established to quantify maternal plasma DNA sequences for the non-invasive prenatal detection of fetal trisomy 21. Findings: ChAPDes could output 21,772 candidate primer/probe sets for trisomy 13, 18, 21 and sex chromosome aneuploidies within 2 working days. Clinical evaluation of the multiplex multicolour melting curve analysis involving 463 fetal genomic DNA samples revealed a sensitivity of 100% and specificity of 99.64% in comparison with the reference methods. Using the established digital PCR protocol, we correctly identified two trisomy 21 fetuses and thirteen euploid foetuses from the maternal plasma samples. Interpretation: The combination of ChAPDes with digital PCR detection could facilitate the use of SD as potential biomarkers for the non-invasive prenatal testing of fetal chromosomal aneuploidies.

【 授权许可】

Unknown