title: Fetal Genotyping in Maternal Blood by Digital PCR: Towards NIPD of Monogenic Disorders Independently of Parental Origin.
abstract: OBJECTIVE
  To date, non-invasive prenatal diagnosis (NIPD) of monogenic disorders has been limited to cases with a paternal origin. This work shows a validation study of the Droplet Digital PCR (ddPCR) technology for analysis of both paternally and maternally inherited fetal alleles. For the purpose, single nucleotide polymorphisms (SNPs) were studied with the only intention to mimic monogenic disorders.
  
  
  METHODS
  NIPD SNP genotyping was performed by ddPCR in 55 maternal plasma samples. In 19 out of 55 cases, inheritance of the paternal allele was determined by presence/absence criteria. In the remaining 36, determination of the maternally inherited fetal allele was performed by relative mutation dosage (RMD) analysis.
  
  
  RESULTS
  ddPCR exhibited 100% accuracy for detection of paternal alleles. For diagnosis of fetal alleles with maternal origin by RMD analysis, the technology showed an accuracy of 96%. Twenty-nine out of 36 were correctly diagnosed. There was one FP and six maternal plasma samples that could not be diagnosed.
  
  
  CONCLUSIONS
  In this study, ddPCR has shown to be capable to detect both paternal and maternal fetal alleles in maternal plasma. This represents a step forward towards the introduction of NIPD for all pregnancies independently of the parental origin of the disease.
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz UAM, CIBERER, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Perlado
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz UAM, CIBERER, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Bustamante-Aragonés
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz UAM, CIBERER, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Donas
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz UAM, CIBERER, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lorda-Sánchez
authors.affiliation: Department of Obstetrics & Gynecology, Fundación Jiménez Díaz-IIS, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Plaza
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz UAM, CIBERER, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodríguez de Alba
mesh_terms: D000483:Alleles; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism*; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004247:DNA