title: Exon arrays reveal alternative splicing aberrations in Parkinson's disease leukocytes.
abstract: BACKGROUND
  Parkinson's disease (PD) is the second most frequent neurodegenerative disease worldwide. Clinical diagnosis can only be made when the vast majority of the dopaminergic cell population has died. However, the cause(s) for sporadic PD is/are yet unclear. Transcript changes have recently been described in PD patients' whole blood cells, but corresponding splicing patterns remained unknown.
  
  
  OBJECTIVE
  To search for alternative splicing aberrations in PD patients' blood leukocytes.
  
  
  METHODS
  We applied exon microarrays to profile PD patients' blood leukocyte mRNA. Exon level splicing analysis served as a basis for downstream classification and functional analyses.
  
  
  RESULTS
  Patients and carefully matched controls were classified by the splicing exon profiles of their leukocyte transcripts. Specifically, many exons were downregulated in PD patients compared to controls. Functional analysis highlighted aberrant splicing of PD-related transcripts and impaired NF-κB cascade and immune response.
  
  
  CONCLUSIONS
  PD patient's blood leukocytes exhibit alternative splicing of numerous transcripts. The aberrant alternative splicing in PD patients' blood cells has potential implications for early diagnosis and future therapeutics.
authors.affiliation: Department of Medical Neurobiology, Hebrew University-Hadassah Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Soreq
authors.forename: Hagai
authors.initials: H
authors.lastname: Bergman
authors.forename: Zvi
authors.initials: Z
authors.lastname: Israel
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger