title: SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy.
abstract: OBJECTIVE
  This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy.
  
  
  METHODS
  Sixteen aneuploid samples, including thirteen 45,X, two 47,XXY, and one 47,XYY, along with 185 euploid controls, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified in a single multiplex polymerase chain reaction assay that targeted 19,488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y, and sequenced. Sequencing results were analyzed using a Bayesian-based maximum likelihood statistical method to determine copy number of interrogated chromosomes, calculating sample-specific accuracies.
  
  
  RESULTS
  Of the samples that passed a stringent quality control metric (93%), the algorithm correctly identified copy number at all five chromosomes in all but one of the 187 samples, for 934/935 correct calls as early as 9.4 weeks of gestation. We detected 45,X with 91.7% sensitivity (CI: 61.5-99.8%) and 100% specificity (CI: 97.9-100%), and 47,XXY and 47,XYY. The average calculated accuracy was 99.78%.
  
  
  CONCLUSIONS
  This method non-invasively detected 45,X, 47,XXY, and 47,XYY fetuses from cell-free DNA isolated from maternal plasma with high calculated accuracies and thus offers a non-invasive method with the potential to function as a routine screen allowing for early prenatal detection of rarely diagnosed yet commonly occurring sex aneuploidies.
authors.affiliation: George Washington University School of Medicine and Health Sciences, Washington, D.C., USA. cssprouse@aol.com
authors.forename: Carole
authors.initials: C
authors.lastname: Samango-Sprouse
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hall
authors.forename: Margaret
authors.initials: M
authors.lastname: Westemeyer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Saucier
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
mesh_terms: D000782:Aneuploidy; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D004247:DNA / Q000097:blood; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005865:Gestational Age; D006801:Humans; D008297:Male; D009006:Monosomy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D012729:Sex Chromosome Aberrations; D014314:Trisomy
chemical_list: D004247:DNA