title: Gene expression in archived newborn blood spots distinguishes infants who will later develop cerebral palsy from matched controls.
abstract: BACKGROUND
  Gene expression in archived newborn blood spots remaining from newborn screening may reflect pathophysiological disturbances useful in understanding the etiology of cerebral palsy (CP).
  
  
  METHODS
  We quantified the expression of gene sets representing four physiological pathways hypothesized to contribute to CP in archived unfrozen residual newborn blood spot specimens from 53 children with CP and 53 age-, gender-, and gestational age-matched controls. We selected four empirical and three canonical gene sets representing the inflammatory, hypoxic, coagulative, and thyroidal pathways and examined mRNA expression using an 8 × 60,000 oligonucleotide microarray. The log2 fold change of gene expression between matched cases and controls was analyzed using the generally applicable gene set enrichment method.
  
  
  RESULTS
  The empirical inflammatory and empirical hypoxic gene sets were significantly downregulated in term-born CP cases (n = 33) as compared with matched controls (P = 0.0007 and 0.0009, respectively), whereas both gene sets were significantly upregulated (P =0.0055 and 0.0223, respectively) in preterm-born CP cases (n = 20). The empirical thyroidal gene set was significantly upregulated in preterm-born CP cases (P = 0.0023).
  
  
  CONCLUSIONS
  The newborn blood spot transcriptome can serve as a platform for investigating distinctive gene expression patterns in children who later develop CP.
authors.affiliation: Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Nhan Thi
authors.initials: NT
authors.lastname: Ho
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: Wenjiang
authors.initials: W
authors.lastname: Fu
authors.forename: Julia
authors.initials: J
authors.lastname: Busik
authors.forename: Sok Kean
authors.initials: SK
authors.lastname: Khoo
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Madeleine
authors.initials: M
authors.lastname: Lenski
authors.forename: Julia
authors.initials: J
authors.lastname: Wirth
authors.forename: Edward
authors.initials: E
authors.lastname: Hurvitz
authors.forename: Nancy
authors.initials: N
authors.lastname: Dodge
authors.forename: James
authors.initials: J
authors.lastname: Resau
authors.forename: Nigel
authors.initials: N
authors.lastname: Paneth
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D059788:Dried Blood Spot Testing; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers