Gene expression profiles stratified according to type 1 diabetes mellitus susceptibility regions.
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.
Rassi
Diane Meyre
DM
Molecular Immunogenetics Group, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. dianerassi@usp.br
Junta
Cristina Moraes
CM
Fachin
Ana Lúcia
AL
Sandrin-Garcia
Paula
P
Mello
Stephano
S
Silva
Guilherme Liberato
GL
Evangelista
Adriane Feijó
AF
Magalhães
Danielle Aparecida
DA
Wastowski
Isabela Jubé
IJ
Crispim
Janaína Oliveira
JO
Martelli-Palomino
Gustavo
G
Fernandes
Ana Paula Mores
AP
Deghaide
Neife N H S
NN
Foss-Freitas
Maria Cristina
MC
Foss
Milton César
MC
Soares
Christiane Pienna
CP
Sakamoto-Hojo
Elza Tieme
ET
Passos
Geraldo Aleixo Silva
GA
Donadi
Eduardo Antônio
EA
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