title: Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida.
abstract: BACKGROUND
  Based on studies in animals and humans, PAX3 and T (brachyury) are candidate genes for spina bifida. However, neither gene has been definitively identified as a risk factor for this condition.
  
  
  METHODS
  Sanger sequencing was used to identify variants in all PAX3 and T exons and promoter regions in 114 spina bifida cases. For known variants, allele frequencies in cases were compared with those from public databases using unadjusted odds ratios. Novel variants were genotyped in parents and assessed for predicted functional impact.
  
  
  RESULTS
  We identified common variants in PAX3 (n = 2) and T (n = 3) for which the allele frequencies in cases were significantly different from those reported in at least one public database. We also identified novel variants in both PAX3 (n = 11) and T (n = 1) in spina bifida cases. Several of the novel PAX3 variants are predicted to be highly conserved and/or impact gene function or expression.
  
  
  CONCLUSIONS
  These studies provide some evidence that common variants of PAX3 and T are associated with spina bifida. Rare and novel variants in these genes were also identified in affected individuals. However, additional studies will be required to determine whether these variants influence the risk of spina bifida.
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas.
authors.forename: A J
authors.initials: AJ
authors.lastname: Agopian
authors.forename: Angela D
authors.initials: AD
authors.lastname: Bhalla
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: Anshuman
authors.initials: A
authors.lastname: Sewda
authors.forename: Colin
authors.initials: C
authors.lastname: Stuart
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhong
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
mesh_terms: D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D005326:Fetal Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D016017:Odds Ratio; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D016135:Spinal Dysraphism / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics*; D014481:United States; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C489409:PAX3 protein, human
keywords: PAX3; T locus; genetic epidemiology; myelomeningocele; sequencing; spina bifida; word
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