Yijun Song1, Xiya Zhou1, Saiqiong Huang1, Xiaohong Li1, Qingwei Qi1, Yulin Jiang1, Yiqian Liu2, Chengcheng Ma2, Zhifeng Li2, Mengnan Xu2, David S Cram3, Juntao Liu4. 1. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China. 2. Berry Genomics C., Limited, Beijing, China. 3. Berry Genomics C., Limited, Beijing, China. Electronic address: david.cram@berrygenomics.com. 4. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China. Electronic address: tao_aus@hotmail.com.
Abstract
BACKGROUND: Calculation of the fetal DNA fraction (FF) is important for reliable and accurate noninvasive prenatal testing (NIPT) for fetal genetic abnormalities. The aim of the study was to develop and validate a novel method for FF determination. METHODS: FF was calculated using the chromosome Y (ChrY) sequence read assay and by circulating single molecule amplification and re-sequencing technology of 76 autosomal SNPs. RESULTS: By Pearson correlation for FF (4.73-22.11%) in 33 male pregnancy samples, the R(2) co-efficient for the 76-SNP versus the ChrY assay was 0.9572 (p<0.001). In addition, the co-efficient of variation (CV) of FF measurement by the 76-SNP assay was low (0.15-0.35). As a control, the FF measurement for four non-pregnant plasma samples was virtually zero. In prospective longitudinal studies of 14 women with normal pregnancies, FF generally increased with gestational age. However, in eight women (71%) there was a significant decrease in FF between the first trimester (11-13 weeks) and the second trimester (15-19 weeks), and this was attributable to significant maternal weight gain. CONCLUSIONS: The novel 76-SNP cSMART assay has the precision to accurately measure FF in all pregnancies at a detection threshold of 5%. Based on FF trends in individual pregnancies, our results suggest that the end of the first trimester may be a more optimal window for performing NIPT.
BACKGROUND: Calculation of the fetal DNA fraction (FF) is important for reliable and accurate noninvasive prenatal testing (NIPT) for fetal genetic abnormalities. The aim of the study was to develop and validate a novel method for FF determination. METHODS: FF was calculated using the chromosome Y (ChrY) sequence read assay and by circulating single molecule amplification and re-sequencing technology of 76 autosomal SNPs. RESULTS: By Pearson correlation for FF (4.73-22.11%) in 33 male pregnancy samples, the R(2) co-efficient for the 76-SNP versus the ChrY assay was 0.9572 (p<0.001). In addition, the co-efficient of variation (CV) of FF measurement by the 76-SNP assay was low (0.15-0.35). As a control, the FF measurement for four non-pregnant plasma samples was virtually zero. In prospective longitudinal studies of 14 women with normal pregnancies, FF generally increased with gestational age. However, in eight women (71%) there was a significant decrease in FF between the first trimester (11-13 weeks) and the second trimester (15-19 weeks), and this was attributable to significant maternal weight gain. CONCLUSIONS: The novel 76-SNP cSMART assay has the precision to accurately measure FF in all pregnancies at a detection threshold of 5%. Based on FF trends in individual pregnancies, our results suggest that the end of the first trimester may be a more optimal window for performing NIPT.
Authors: Matthew S Hestand; Mark Bessem; Peter van Rijn; Renee X de Menezes; Daoud Sie; Ingrid Bakker; Elles M J Boon; Erik A Sistermans; Marjan M Weiss Journal: Eur J Hum Genet Date: 2018-09-25 Impact factor: 4.246