Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544162 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFNβ stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs. Total RNA obtained from isolated PBMC extracted from healthy subjects and in vitro stimulated or not with Interferon-β (100IU/mL) for 18h
2015-08-03 | E-GEOD-71634 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variant found in patients, but not those found exclusively in controls, impair suppression of IRF and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.
2019-05-01 | GSE126307 | GEO
Project description:This experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFNβ stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs.
2015-08-03 | GSE71634 | GEO
Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.
2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress
Project description:Background & Aims: Most inflammatory bowel diseases (IBDs) are classic polygenic disorders represented by common alleles. However, multiple determinants of very early-onset IBD characterized by a more extensive disease course remain largely unknown. The present study aimed to define the genetic architecture of pediatric and adult-onset IBDs in the Polish population. Results: Of 82 SNPs validated/replicated for association with IBD, a novel BRD2 (rs1049526) association was found in both pediatric (OR= 2.35) and adult (OR= 2.66) patients. Thirty SNPs were shared between pediatric and adult patients; 22 and 30 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare/infrequent, potentially deleterious variants in IBD-associated or innate immunity-associated genes. Both groups of variants were over-represented in affected children. Two highly deleterious homozygous variants, HLA-DRB1 c.565_566insC and NCF4 p.Arg8Trp, were found in two affected children, and WAS p.Glu131Lys was found in one child and one adult patient. Conclusions: Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare/low frequency deleterious variants in affected children suggests a contribution by yet unexplained genetic components.
2017-01-01 | GSE79094 | GEO
Project description:NEK1 variants in a cohort of Italian patients with Amyotrophic Lateral Sclerosis
| PRJEB51456 | ENA
Project description:Functional rare and low frequency variants in BLK and BANK contribute to human lupus pathogenesis
| PRJNA522453 | ENA
Project description:This experiment was carried out in the context of a whole-genome sequencing study in 4 affected and 4 unaffected relatives of a consanguineous Italian family characterized by the high prevalence of multiple sclerosis. These data were used to evaluate differences in GRAMD1B gene expression in whole blood comparing healthy and affected subjects of the family. Functional experiments have been subsequently performed to evaluate the involvement of this gene in multiple sclerosis.
2018-08-01 | GSE103005 | GEO