title: Gene expression profiles stratified according to type 1 diabetes mellitus susceptibility regions.
abstract: The MHC region (6p21) aggregates the major genes that contribute to susceptibility to type 1 diabetes (T1D). Three additional relevant susceptibility regions mapped on chromosomes 1p13 (PTPN22), 2q33 (CTLA-4), and 11p15 (insulin) have also been described by linkage studies. To evaluate the contribution of these susceptibility regions and the chromosomes that house these regions, we performed a large-scale differential gene expression on lymphomononuclear cells of recently diagnosed T1D patients, pinpointing relevant modulated genes clustered in these regions and their respective chromosomes. A total of 4608 cDNAs from the IMAGE library were spotted onto glass slides using robotic technology. Statistical analysis was carried out using the SAM program, and data regarding gene location and biological function were obtained at the SOURCE, NCBI, and FATIGO programs. Three induced genes were observed spanning around the MHC region (6p21-6p23), and seven modulated genes (5 repressed and 2 repressed) were seen spanning around the 6q21-24 region. Additional modulated genes were observed in and around the 1p13, 2q33, and 11p15 regions. Overall, modulated genes in these regions were primarily associated with cellular metabolism, transcription factors and signaling transduction. The differential gene expression characterization may identify new genes potentially involved with diabetes pathogenesis.
authors.affiliation: Molecular Immunogenetics Group, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. dianerassi@usp.br
authors.forename: Diane Meyre
authors.initials: DM
authors.lastname: Rassi
authors.forename: Cristina Moraes
authors.initials: CM
authors.lastname: Junta
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Fachin
authors.forename: Paula
authors.initials: P
authors.lastname: Sandrin-Garcia
authors.forename: Stephano
authors.initials: S
authors.lastname: Mello
authors.forename: Guilherme Liberato
authors.initials: GL
authors.lastname: Silva
authors.forename: Adriane Feijó
authors.initials: AF
authors.lastname: Evangelista
authors.forename: Danielle Aparecida
authors.initials: DA
authors.lastname: Magalhães
authors.forename: Isabela Jubé
authors.initials: IJ
authors.lastname: Wastowski
authors.forename: Janaína Oliveira
authors.initials: JO
authors.lastname: Crispim
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli-Palomino
authors.forename: Ana Paula Mores
authors.initials: AP
authors.lastname: Fernandes
authors.forename: Neife N H S
authors.initials: NN
authors.lastname: Deghaide
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Foss-Freitas
authors.forename: Milton César
authors.initials: MC
authors.lastname: Foss
authors.forename: Christiane Pienna
authors.initials: CP
authors.lastname: Soares
authors.forename: Elza Tieme
authors.initials: ET
authors.lastname: Sakamoto-Hojo
authors.forename: Geraldo Aleixo Silva
authors.initials: GA
authors.lastname: Passos
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D016000:Cluster Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis