Evaluation of sex-specific gene expression in archived dried blood spots (DBS)

Int J Mol Sci. 2012;13(8):9599-9608. doi: 10.3390/ijms13089599. Epub 2012 Aug 2.


Screening newborns for treatable serious conditions is mandated in all US states and many other countries. After screening, Guthrie cards with residual blood (whole spots or portions of spots) are typically stored at ambient temperature in many facilities. The potential of archived dried blood spots (DBS) for at-birth molecular studies in epidemiological and clinical research is substantial. However, it is also challenging as analytes from DBS may be degraded due to preparation and storage conditions. We previously reported an improved assay for obtaining global RNA gene expression from blood spots. Here, we evaluated sex-specific gene expression and its preservation in DBS using oligonucleotide microarray technology. We found X inactivation-specific transcript (XIST), lysine-specific demethylase 5D (KDM5D) (also known as selected cDNA on Y, homolog of mouse (SMCY)), uncharacterized LOC729444 (LOC729444), and testis-specific transcript, Y-linked 21 (TTTY21) to be differentially-expressed by sex of the newborn. Our finding that trait-specific RNA gene expression is preserved in unfrozen DBS, demonstrates the technical feasibility of performing molecular genetic profiling using such samples. With millions of DBS potentially available for research, we see new opportunities in using newborn molecular gene expression to better understand molecular pathogenesis of perinatal diseases.

Keywords: archived dried blood spots (DBS); gene expression; microarray; molecular genetic profiling; sex-specific.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Biomarkers / analysis*
  • Blood Specimen Collection*
  • Case-Control Studies
  • Cerebral Palsy / blood
  • Cerebral Palsy / diagnosis
  • Cerebral Palsy / genetics*
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling*
  • Histone Demethylases / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Mice
  • Minor Histocompatibility Antigens
  • Neonatal Screening*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics
  • Real-Time Polymerase Chain Reaction


  • Biomarkers
  • Minor Histocompatibility Antigens
  • RNA, Long Noncoding
  • XIST non-coding RNA
  • Histone Demethylases
  • KDM5D protein, human