title: Splice site SNPs of phospholipase PLCXD3 are significantly associated with variant and sporadic Creutzfeldt-Jakob disease.
abstract: BACKGROUND
  Variant Creutzfeldt-Jakob disease is an infectious, neurodegenerative, protein-misfolding disease, of the prion disease family, originally acquired through ingestion of meat products contaminated with bovine spongiform encephalopathy (BSE). Public health concern was increased by the discovery of human-to-human transmission via blood transfusion. This study has verified a novel genetic marker linked to disease risk.
  
  
  METHODS
  SNP imputation and association testing indicated those genes that had significant linkage to disease risk and one gene was investigated further with Sanger resequencing. Results from variant Creutzfeldt-Jakob disease were compared with those from sporadic (idiopathic) Creutzfeldt-Jakob disease and published controls.
  
  
  RESULTS
  The most significant disease risk, in addition to the prion protein gene, was for the phosphatidylinositol-specific phospholipase C, X domain containing 3 (PLCXD3) gene. Sanger resequencing of CJD patients across a region of PLCXD3 with known variants confirmed three SNPs associated with variant and sporadic CJD.
  
  
  CONCLUSIONS
  These data provide the first highly significant confirmation of SNP allele frequencies for a novel CJD candidate gene providing new avenues for investigating these neurodegenerative prion diseases. The phospholipase PLCXD3 is primarily expressed in the brain and is associated with lipid catabolism and signal transduction.
authors.affiliation: National CJD Research & Surveillance Unit, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. m.bishop@ed.ac.uk.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Bishop
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanchez-Juan
authors.forename: Richard S G
authors.initials: RS
authors.lastname: Knight
mesh_terms: D001483:Base Sequence; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D010738:Type C Phospholipases / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D010738:Type C Phospholipases
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