title: Quantitation of fetal DNA fraction in maternal plasma using circulating single molecule amplification and re-sequencing technology (cSMART).
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.
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Xiya
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Saiqiong
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Berry Genomics C., Limited, Beijing, China.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Berry Genomics C., Limited, Beijing, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Ma
authors.affiliation: Berry Genomics C., Limited, Beijing, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Berry Genomics C., Limited, Beijing, China.
authors.forename: Mengnan
authors.initials: M
authors.lastname: Xu
authors.affiliation: Berry Genomics C., Limited, Beijing, China. Electronic address: david.cram@berrygenomics.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China. Electronic address: tao_aus@hotmail.com.
authors.forename: Juntao
authors.initials: J
authors.lastname: Liu
mesh_terms: D004247:DNA / Q000097:blood* / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D008297:Male; D009035:Mothers; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA
keywords: Circulating single molecule amplification and re-sequencing technology; Noninvasive prenatal diagnosis; Single nucleotide polymorphism; fetal fraction