Microarray expression analysis of PRF1 (perforin 1) haplotypes in patients with primary progressive multiple sclerosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE23205 | GEO | 2010/07/28
SECONDARY ACCESSION(S): PRJNA131645
REPOSITORIES: GEO
Similar Datasets
Project description:A genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes. Number of samples analyzed: 10 Protective haplotype samples: UOM982, EMA1473, MMC-998, CDP1842 Risk haplotype samples: UUS1554, RAU1550, RPS1011, AGS1013, PFB1530, MGA1014
2010-07-28 | E-GEOD-23205 | biostudies-arrayexpress
Project description:Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R. Samples of CD4+ cells were obtained from 7 MS patients (homozygous for Hap1 (3), Hap2 (2), Hap3 (2)). CD4+ cells were collected from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and CD4+ cells were purified by magnetic bead separation. Purity and viability of cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human Gene 1.0 ST Array (affymetrix). IL7R haplotypes and susceptibility to develop MS: Hap1 homozygous <-> Risk <-> positive effect on MS susceptibility Hap2 homozygous <-> Hap2 <-> neutral effect on MS susceptibility Hap3 homozygous <-> Prot <-> neutral effect on MS susceptibility [Note: Haplotype nomenclature subject to revision.]
2015-04-14 | E-GEOD-37584 | biostudies-arrayexpress
Project description:Transcription profiling of peripheral blood from patients with primary progressive multiple sclerosis to compare risk and protective PRF1 haplotypes
2014-07-03 | E-GEOD-23205 | ExpressionAtlas
Project description:Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R.
2015-04-14 | GSE37584 | GEO
Project description:Multiple sclerosis (MS) is the most common neurological disorder in young adults and is classically defined as a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although MS affects millions of people worldwide, its underlying cause remains unknown making discovery of effective treatments challenging. Whether intrinsic or extrinsic factors contribute to MS initiation and progression is still unclear. This is especially true for primary progressive MS (PPMS), the rarest form of the disease, in which progressive and irreversible loss of neurological function is often observed in the absence of an overt immune-inflammatory response. To test the hypothesis that intrinsic dysfunction in oligodendrocytes (OLs), the primary targets of damage in MS, may contribute to PPMS etiopathology, we differentiated human induced pluripotent stem cell (hiPSC) lines derived from PPMS and healthy individuals into mature OLs to compare their transcriptional profile. PPMS derived OLs displayed hundreds of differentially expressed genes compared to control OLs, many associated with cell adhesion, apoptosis and inflammation, including the inflammasome component Nlrp2, which was highly upregulated. NLRP2 immunoreactivity in OLs was confirmed in post-mortem PPMS brain tissues, with higher expression than in control tissues. Altogether, our findings suggest that mature OLs in PPMS affected individuals carry intrinsic abnormalities that could contribute, at least in part, to the pathophysiology of this form of the disease.
2022-08-26 | GSE211739 | GEO
Project description:This study provides an overview of the transcriptional signature of oligodendrocyte progenitor cells (OPCs) exposed to the CSF collected from multiple sclerosis patients with either a relapsing remitting disease course (RRMS) or a confirmed primary progressive diagnosis (PPMS). Using an Affymetrix microarray we were able to detect a set of common and unique genes for each treatment group. Gene ontology analysis revealed a common group of genes involved in protein transport, actin dynamics and response to stress and DNA damage, while the RRMS-specific genes were grouped according to protein complex biogenesis, nuclear transport and RNA processing. The transcriptional signature of progenitors exposed to PPMS was characterized by an up-regulation of the pro-differentiation adhesion molecule Lgals3. We confirmed increased protein levels of its gene product,product; galectin-3 in proliferating OPCs incubated with CSF from PPMS patients and also found a four-fold increase in mRNA transcript levels of galectin-3 in human post-mortem normal-appearing white matter samples of primary progressive MS patients when compared to non-neurological controls. This study will help to better understand the common and specific transcriptional changes induced in the different subtypes of MS and therefore find more specific molecular targets for each disease subtype. Comparison of transcriptional signature by microarray analysis of OPCs treated with RRMS and PPMS CSF.
2015-06-19 | E-GEOD-60881 | biostudies-arrayexpress
Project description:Expansion of the hexanucleotide repeat (HR) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasians. All C9orf72 ALS/FTD patients share a common risk (R) haplotype, but its single nucleotide polymorphism (SNP) signature has not been fully characterized. Here, we characterized the C9orf72 haplotypes in Europeans and created a detailed molecular map, including HR length, for each haplotype. By analyzing RNA-seq reads and sequencing chromatograms that overlap with heterozygous SNP sites, we identified allelic differences in C9orf72 expression in normal subjects and ALS patients. In cells from healthy individuals, upstream promoter transcript levels increased with increased HR length. Intron 1 levels were higher in one of the non-R haplotypes due to SNP variation, and in R haplotype with 10 or more HR units. In pathological HR expansion, we observed the highest levels of intron 1 that were accompanied by aberrantly spliced transcripts at cryptic donor sites downstream of the expanded HR. Intron 1 retention was associated with sequential intron 2 retention. The SNP signature of C9orf72 haplotypes described here enables allele-specific analysis of transcriptional products and may pave the way to allele-specific therapeutic strategies.
2021-03-01 | GSE162943 | GEO
Project description:Total mRNA seq was perfomed on human fetal gut tissue at CS22 on 3 samples having different RET haplotype which progressively reduce expression of RET. R haplotypes are resistant and S haplotypes are susceptible to Hirschsprung disease
2018-10-30 | GSE111341 | GEO
Project description:This study provides an overview of the transcriptional signature of oligodendrocyte progenitor cells (OPCs) exposed to the CSF collected from multiple sclerosis patients with either a relapsing remitting disease course (RRMS) or a confirmed primary progressive diagnosis (PPMS). Using an Affymetrix microarray we were able to detect a set of common and unique genes for each treatment group. Gene ontology analysis revealed a common group of genes involved in protein transport, actin dynamics and response to stress and DNA damage, while the RRMS-specific genes were grouped according to protein complex biogenesis, nuclear transport and RNA processing. The transcriptional signature of progenitors exposed to PPMS was characterized by an up-regulation of the pro-differentiation adhesion molecule Lgals3. We confirmed increased protein levels of its gene product,product; galectin-3 in proliferating OPCs incubated with CSF from PPMS patients and also found a four-fold increase in mRNA transcript levels of galectin-3 in human post-mortem normal-appearing white matter samples of primary progressive MS patients when compared to non-neurological controls. This study will help to better understand the common and specific transcriptional changes induced in the different subtypes of MS and therefore find more specific molecular targets for each disease subtype.
2015-06-19 | GSE60881 | GEO