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Systematic micro-array based identification of placental mRNA in maternal plasma: towards non-invasive prenatal gene expression profiling
  1. N B Y Tsui1,
  2. S S C Chim1,
  3. R W K Chiu1,
  4. T K Lau2,
  5. E K O Ng1,
  6. T N Leung2,
  7. Y K Tong1,
  8. K C A Chan1,
  9. Y M D Lo1
  1. 1Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR
  2. 2Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR
  1. Correspondence to:
 Y M D Lo
 Department of Chemical Pathology, The Chinese University of Hong Kong, Room 38023, 1/F Clinical Sciences Building, Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, New Territories, Hong Kong Special Administrative Region, China;

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The discovery of fetal DNA in the plasma of pregnant women1 has led to the development of promising approaches for non-invasive prenatal diagnosis.2–6 However, as fetal and maternal DNA species co-exist in maternal plasma, these DNA based diagnostic applications depend largely on the use of genetic markers that would allow the discrimination between fetal and maternal DNA (for example, the Y chromosome of a male fetus), and thus, a particular genetic marker could generally only be used in a proportion of pregnancies. This situation has prompted a quest by many laboratories to develop fetal nucleic acid markers that are independent of sex or polymorphism.

The detection of fetal RNA in maternal plasma7 offers new possibilities for non-invasive prenatal investigation. This field has recently taken on new momentum as robust methods for plasma RNA extraction have been developed8 and circulating RNA has been shown to be surprisingly stable,9 possibly through an association with particulate matter.8 Furthermore, recent studies have identified the placenta as a significant source of such circulating fetal RNA.10 Hence, placental expressed mRNA transcripts, such as those coding for human placental lactogen (hPL), human chorionic gonadotropin β subunit (βhCG),10 and corticotropin releasing hormone (CRH),11 have been shown to be detectable in maternal plasma. Quantitative assays have been developed for the measurement of these circulating mRNA transcripts.8 The pregnancy specificity of these mRNA species has been demonstrated by their rapid clearance from maternal plasma after delivery.10,11 Thus, the detection in maternal plasma of mRNA transcripts derived from the plasma offers new avenues for the development of fetal specific nucleic acid markers that are independent of sex and polymorphism for the non-invasive prenatal assessment of all pregnancies.12 The clinical value of such an approach has …

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  • This project is supported by the Innovation and Technology Fund (ITS/195/01), a Central Allocation Grant (CUHK 1/03C), and an Earmarked Research Grant (CUHK 4474/03M) from the Hong Kong Research Grants Council.

  • Conflicts of interest: The Chinese University of Hong Kong has filed patents on fetal nucleic acid analysis from maternal plasma. Aspects of fetal nucleic acid analysis in maternal plasma have been licensed to BTG and Plasmagene. YM Dennis Lo is a consultant and shareholder of Plasmagene.