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- Delgado-Vega, Angélica M., et al.
(författare)
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Whole Exome Sequencing of Patients from Multicase Families with Systemic Lupus Erythematosus Identifies Multiple Rare Variants
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8775-
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Tidskriftsartikel (refereegranskat)abstract
- In an effort to identify rare alleles associated with SLE, we have performed whole exome sequencing of the most distantly related affected individuals from two large Icelandic multicase SLE families followed by Ta targeted genotyping of additional relatives. We identified multiple rare likely pathogenic variants in nineteen genes co-segregating with the disease through multiple generations. Gene co-expression and protein-protein interaction analysis identified a network of highly connected genes comprising several loci previously implicated in autoimmune diseases. These genes were significantly enriched for immune system development, lymphocyte activation, DNA repair, and V(D)J gene recombination GO-categories. Furthermore, we found evidence of aggregate association and enrichment of rare variants at the FAM71E1/EMC10 locus in an independent set of 4,254 European SLE-cases and 4,349 controls. Our study presents evidence supporting that multiple rare likely pathogenic variants, in newly identified genes involved in known disease pathogenic pathways, segregate with SLE at the familial and population level.
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| 2. |
- Gubanova, N. V., et al.
(författare)
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Glioblastoma gene network reconstruction and ontology analysis by online bioinformatics tools
- 2021
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Ingår i: Journal of Integrative Bioinformatics. - : Walter de Gruyter GmbH. - 1613-4516. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma is the most aggressive type of brain tumors resistant to a number of antitumor drugs. The problem of therapy and drug treatment course is complicated by extremely high heterogeneity in the benign cell populations, the random arrangement of tumor cells, and polymorphism of their nuclei. The pathogenesis of gliomas needs to be studied using modern cellular technologies, genome- and transcriptome-wide technologies of high-throughput sequencing, analysis of gene expression on microarrays, and methods of modern bioinformatics to find new therapy targets. Functional annotation of genes related to the disease could be retrieved based on genetic databases and cross-validated by integrating complementary experimental data. Gene network reconstruction for a set of genes (proteins) proved to be effective approach to study mechanisms underlying disease progression. We used online bioinformatics tools for annotation of gene list for glioma, reconstruction of gene network and comparative analysis of gene ontology categories. The available tools and the databases for glioblastoma gene analysis are discussed together with the recent progress in this field.
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| 3. |
- Oparina, Nina Y., et al.
(författare)
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PXK locus in systemic lupus erythematosus : fine mapping and functional analysis reveals novel susceptibility gene ABHD6
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Methods Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Results Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. Conclusions These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.
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