title: Evaluation of sex-specific gene expression in archived dried blood spots (DBS).
abstract: 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.
authors.affiliation: Program of Biospecimen Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Resau
authors.affiliation: Department of Epidemiology & Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI 48823, USA.
authors.forename: Nhan T
authors.initials: NT
authors.lastname: Ho
authors.affiliation: Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Dykema
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Faber
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Busik
authors.affiliation: Department of Mathematics & Computer Science, Fayetteville State University, Fayetteville, NC 28301, USA.
authors.forename: Radoslav Z
authors.initials: RZ
authors.lastname: Nickolov
authors.affiliation: Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Furge
authors.affiliation: Department of Epidemiology & Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI 48823, USA.|Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48823, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Paneth
authors.affiliation: Program of Biospecimen Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Jewell
authors.affiliation: Laboratory of Microarray Technology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Sok Kean
authors.initials: SK
authors.lastname: Khoo
mesh_terms: D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001800:Blood Specimen Collection; D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D015778:Minor Histocompatibility Antigens; D015997:Neonatal Screening; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D015778:Minor Histocompatibility Antigens; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; D056466:Histone Demethylases; C095561:KDM5D protein, human