Feasibility Study Of Non-invasive Prenatal Testing Of Fetal Balanced Chromosomal Rearrangement From Maternal Plasma

Balanced translocation is the most common chromosomal structural abnormality at present.Most of the carriers have no obvious abnormal phenotype until the occurrence of adverse pregnancy history.For these cohorts,to know the inheritance of the fetus at an early stage has important guiding significance for reproductive health.At present,the prenatal testing is mainly carried out by invasive diagnosis,and there is still no effective non-invasive prenatal testing method in clinical setting.This study mainly uses high-throughput sequencing,bioinformatics methods and molecular biology techniques for cell-free DNA to try to develop non-invasive prenatal testing based on maternal plasma for fetal paternal balanced translocation.In this study,the cohort sample of the known father as the balanced translocation carrier was used as the research object,and the high-throughput sequencing technology was used to analyze the precise breakpoint information of the father's balanced translocation.Then,according to the father's balanced translocation breakpoint,specific primers will be designed for cell-free fetal DNA.A series of balanced translocation positive simulation sample was established,and the limit of the detection was determined by detecting samples in different fetal concentration gradients.Then combining non-invasive testing of fetal chromosomal aneuploidy and large copy number variation to analyze the genetic status of fetal balanced translocation,providing an indication of the inheritance of fetal balanced translocation.A family whose father was a carrier of balanced translocation was recruited in this study.The pregnant women's plasma was collected both in the first-and second-trimester to perform the non-invasive prenatal screening of fetal chromosomal aneuploidy and copy number variation.Specific primers were designed with father's precise balanced translocation breakpoints and the limit of detection can be determined to be as low as 3.5%fetal concentration.The test results showed that the fetus has a balanced translocation between chromosome 5 and 12,and it was determined to be a balanced translocation carrier as her father.The fetal amniocyte in the mother's amniocentesis were collected and verified,and the results were consistent with the test results.This study proposes a non-invasive prenatal detection of fetal paternal balanced translocation.It can simultaneous performs non-invasive prenatal detection of balanced translocations while performing fetal chromosomal aneuploidy screening.It is highly operable and can assist the current clinical non-invasive prenatal testing,providing early clinical indications to the patients.