Investigation of INDEL variants in apoptosis: the relevance to gastric cancer
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PROVIDER: PRJEB40351 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND:Apoptosis is a type of cell death involved in different pathways inherent to the cell and the evasion from this mechanism has been related to cancer, although this process remains not very well comprehended. Gastric cancer (GC) is one of the most incident and aggressive types of cancer worldwide. In this study, we analyzed the distribution of INDEL variants in GC patients (Case) and individuals from the general population (Control) from the Amazon region, in which GC is remarkably frequent. METHODS:A panel of nine INDEL markers in apoptosis-related genes (BCL2 rs11269260, CASP3 rs4647655, CASP8 rs3834129 and rs59308963, CASP9 rs4645982 and rs61079693, FADD rs4197, FAS rs10562972 and TP53 rs17880560) was developed and genotyped by multiplex PCR in both groups. RESULTS:In our analyses, only marker rs4197 (FADD gene) was associated to GC development as follows: INS/DEL genotype of rs4197 increasing in about 2-fold the chances of developing this type of cancer (P?=?0.046; OR?=?1.940; 95%CI?=?1.011-3.725). CONCLUSION:Our results suggest that rs4197 (FADD gene) might play a role in gastric carcinogenesis in the investigated population. More studies are needed to clarify this relation. Here, we highlight the importance of investigating INDEL variants in genes involved in apoptosis.
| S-EPMC7574166 | biostudies-literature
Project description:Gene variants resulting in insertions or deletions of amino acid residues (indels) have important consequences for evolution and are often linked to disease, yet compared to missense variants the effects of indels are poorly understood and ineptly predicted. To approach this issue, we developed a sensitive protein folding sensor based on complementation of uracil auxotrophy in yeast by circular permutated orotate phosphoribosyltransferase (CPOP). The sensor accurately reports on the folding of disease-linked missense variants and artificially designed proteins. Applying the folding sensor to a saturated library of single amino acid indel variants in human DHFR revealed that most regions which tolerate indels are confined to internal loops and the N- and C-termini. Surprisingly, indels are also allowed at a central α-helix. Several indels are temperature-sensitive and the folding of most indels is rescued upon binding to the competitive DHFR inhibitor methotrexate. Predictions using Rosetta and AlphaFold2 correlate with the observed effects, suggesting that most indels operate by destabilizing the native fold and that these computational tools may be useful for classification of indels observed in population sequencing.
2024-07-25 | GSE270811 | GEO
Project description:Amino acid insertions and deletions (indels) are an abundant class of genetic variants. However, compared to substitutions, the effects of indels are not well understood and poorly predicted. Here we address this shortcoming by performing deep indel mutagenesis (DIM) of structurally diverse proteins. Indel tolerance is strikingly different to substitution tolerance and varies extensively both between different proteins and within different regions of the same protein. Although state of the art variant effect predictors perform poorly on indels, we show that both experimentally-measured and computationally-predicted substitution scores can be repurposed as good indel variant effect predictors by incorporating information on protein secondary structures. Quantifying the effects of indels on protein-protein interactions reveals that insertions can be an important class of gain-of-function variants. Our results provide an overview of the impact of indels on proteins and a method to predict their effects genome-wide.
2023-09-28 | GSE244096 | GEO
Project description:Systematic characterization of indel variants using a yeast-based protein folding sensor
| PRJNA1128549 | ENA
Project description:CDC20 promoter variants are present in ~26% of cutaneous melanomas. We generated an indel in the promoter of CDC20 and performed RNA-sequencing to determine the effect on CDC20 expression and other secondary transcriptional changes.
2023-11-01 | GSE206639 | GEO
Project description:Discovering Rare Variants in Gastric Cancer Susceptibility in Gastric Cancer Family
| PRJEB29071 | ENA
Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility We performed an exome chip-based array study in 329 gastric cancer cases and 683 controls.
2014-06-11 | E-GEOD-58356 | biostudies-arrayexpress
Project description:SpCas9 INDEL frequency and HITI was evaluated at the on-target site of guide RNA targeting either the mouse or pig rhodopsin by next-generation sequencing.
2021-11-11 | GSE180875 | GEO
Project description:Cancer Gastric (CG) is a multifactorial disease with an important genetics background, per example copy number variants (CNV). Microarray data analysis were performed to identify CNV that could be contributing to those Mexican patient's clinical phenotypes
2022-04-13 | GSE117093 | GEO
Project description:The gastric epithelial gene responses to Campylobacter concisus infection were investigated by comparative differential expression analysis
2023-12-27 | GSE242316 | GEO