title: Detection of paternal alleles in maternal plasma for non-invasive prenatal diagnosis of beta-thalassemia: a feasibility study in southern Chinese.
abstract: OBJECTIVE
  To evaluate in maternal plasma, the efficacy of detecting the paternal beta-gene mutation and informative single nucleotide polymorphisms (SNPs) linked to the paternal-mutant or -normal allele in non-invasive prenatal diagnosis (NIPND).
  
  
  METHODS
  In 20 at-risk pregnancies, using the allele-specific arrayed primer extension (AS-APEX) technology of the previously published "Thalassemia" array, cyanine-5-deoxycytosine triphosphate (Cy5-dCTP) was incorporated into the extended strands to matched PCR-amplified maternal plasma DNA templates, to detect both the paternal beta-gene mutation and informative paternal SNPs.
  
  
  RESULTS
  Sensitivity experiment showed that 5pg DNA as starting template gave detectable signals on the array. In 13 cases (65%), the paternal-derived beta-gene mutation and/or informative mutant-associated SNP were detected. A subsequent invasive procedure was required to determine if the fetus had a beta-thalassemia (thal) major or minor genotype. In 3 cases (15%), absence of the paternal mutant or mutant-associated SNP excluded a beta-thal major fetus; while in 4 cases (20%), this approach was non-discriminative as both parents carry the same mutation without any informative SNP.
  
  
  CONCLUSIONS
  This approach was useful in 16 out of 20 (80%) pregnancies at risk for beta-thal in southern Chinese.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, Hong Kong.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Chan
authors.forename: Irene
authors.initials: I
authors.lastname: Yam
authors.forename: K Y
authors.initials: KY
authors.lastname: Leung
authors.forename: Mary
authors.initials: M
authors.lastname: Tang
authors.forename: T K
authors.initials: TK
authors.lastname: Chan
authors.forename: Vivian
authors.initials: V
authors.lastname: Chan
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002232:Carbocyanines; D003845:Deoxycytosine Nucleotides; D005220:Fathers; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics
chemical_list: D002232:Carbocyanines; C544355:Cy5-dCTP; D003845:Deoxycytosine Nucleotides; D055544:beta-Globins