title: Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches.
abstract: We performed global RNA transcript analysis and comprehensive gene group analysis of peripheral blood leukocyte (PBL) RNA from two groups of matched sib-pairs that were discordant for either schizophrenia (n = 33 sib-pairs) or bipolar disorder (n = 5 sib-pairs). The pairs chosen for these analyses were selected from families with known patterns of genetic linkage (5q for schizophrenia and 6q for bipolar disorder). At the single gene level, we obtained lists of the transcripts with the most significant changes in expression and from these lists determined those with the highest degree of predictive power for classifying subjects according to diagnosis in these samples. At the gene group level, we comprehensively analyzed pairwise expression changes of more than 4,000 functional groups and cytogenetic locations, and present a novel method of displaying these data that we term "cytogenomic" mapping. Verification of selected changes in expression was performed using quantitative real-time RT-PCR. Our results provide compelling evidence for the utility of analyzing PBL RNA for changes in expression in neuropsychiatric disorders.
authors.affiliation: Center for Neuropsychiatric Genetics, Upstate Medical University, Syracuse, NY 13210, USA. middletf@upstate.edu
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.forename: Carlos N
authors.initials: CN
authors.lastname: Pato
authors.forename: Karen L
authors.initials: KL
authors.lastname: Gentile
authors.forename: Lindsay
authors.initials: L
authors.lastname: McGann
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Brown
authors.forename: Marco
authors.initials: M
authors.lastname: Trauzzi
authors.forename: Heba
authors.initials: H
authors.lastname: Diab
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Morley
authors.forename: Helena
authors.initials: H
authors.lastname: Medeiros
authors.forename: Antonio
authors.initials: A
authors.lastname: Macedo
authors.forename: M Helena
authors.initials: MH
authors.lastname: Azevedo
authors.forename: Michele T
authors.initials: MT
authors.lastname: Pato
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D006239:Haplotypes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics*; D035781:Siblings