title: Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci.
abstract: OBJECTIVE
  This study aims to develop a noninvasive prenatal test on the basis of the analysis of cell-free DNA in maternal blood to detect fetal aneuploidy at chromosomes 13, 18, 21, X, and Y.
  
  
  METHODS
  A total of 166 samples from pregnant women, including 11 trisomy 21, three trisomy 18, two trisomy 13, two 45,X, and two 47,XXY samples, were analyzed using an informatics-based method. Cell-free DNA from maternal blood was isolated, amplified using a multiplex polymerase chain reaction (PCR) assay targeting 11,000 single nucleotide polymorphisms on chromosomes 13, 18, 21, X, and Y in a single reaction, and sequenced. A Bayesian-based maximum likelihood statistical method was applied to determine the chromosomal count of the five chromosomes interrogated in each sample, along with a sample-specific calculated accuracy for each test result.
  
  
  RESULTS
  The algorithm correctly reported the chromosome copy number at all five chromosomes in 145 samples that passed a DNA quality test, for a total of 725/725 correct calls. The average calculated accuracy for these samples was 99.92%. Twenty-one samples did not pass the DNA quality test.
  
  
  CONCLUSIONS
  This informatics-based method noninvasively detected fetuses with trisomy 13, 18, and 21, 45,X, and 47,XXY with high sample-specific calculated accuracies for each individual chromosome and across all five chromosomes.
authors.affiliation: Natera Inc, San Carlos, CA, USA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.forename: George
authors.initials: G
authors.lastname: Gemelos
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.forename: Johan
authors.initials: J
authors.lastname: Baner
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.forename: Nikhil
authors.initials: N
authors.lastname: Chopra
authors.forename: Michael
authors.initials: M
authors.lastname: Dodd
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
mesh_terms: D002877:Chromosomes, Human; D005260:Female; D006801:Humans; D059785:Karyotype; D008297:Male; D062145:Maternal Serum Screening Tests; D011247:Pregnancy; D012729:Sex Chromosome Aberrations; D025064:Sex Chromosome Disorders / Q000175:diagnosis*; D014314:Trisomy / Q000175:diagnosis*