Genotyping of two patients with microdeletions of 16p11.2p12.2 to refine the breakpoint locations
Ontology highlight
ABSTRACT:
INSTRUMENT(S): other
ORGANISM(S): Homo sapiens
SUBMITTER: Lisa Shaffer
PROVIDER: E-MEXP-1148 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Array CGH was performed to identify the breakpoints in 3 cases with deletions of 16p11.2p12.2 and 1 case with a duplication/triplication of 16p11.2p12.2.
2007-09-01 | E-TABM-286 | biostudies-arrayexpress
Project description:Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) are one of the most difficult pathogen to treat. The only drug recently approved by the FDA that is active against CRAB is cefiderocol. However, recent studies have shown higher all-cause mortality rate in the group of patients treated with cefiderocol, that may be due to heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Previous studies showed that adding human fluids to CRAB cultures can lead to CFDC heteroresistance. To better understand the nature of this phenomenon, we carried out molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations. Methods: The CRAB strain AMA40 was cultured in the presence of cefiderocol and human pleural fluid (HPF) to isolate heteroresistant variants. Two of them, AMA40 IHC_1 and IHC_2, were subjected to whole genome sequencing and transcriptomic analysis to identify the mutations and transcriptomic changes responsible for the development of cefiderocol resistance. The impact of mutations on the pharmacodynamic activity of cefiderocol was assessed by susceptibility testing, EDTA and Boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Variants AMA40 IHC_1 and IHC_2 had 53 mutations, forty of which were common to both heteroresistant strains. None of the mutations are located inside genes associated with iron-uptake systems or β-lactam resistance. However, pipA, a gene associated with iron homeostasis in other species, was mutated in heteroresistant strains. Transcriptomic analyses revealed modifications in levels of expression of genes associated with antibiotic resistance. The blaNDM-1, blaADC-2, pbp3, and pbp1 were expressed at higher levels. At the same time, the carO and ompA genes’ expression was reduced. Collateral resistance to amikacin was observed in the heteroresistant variants. Static time-kill assays showed that when CA-MHB was supplemented with human serum albumin, the main protein component of HPF, cefiderocol killing activity was considerably reduced in all three strains. Conclusions: We conclude that heteroresistance to cefiderocol in CRAB, when exposed to fluids containing high HSA, is caused by mutations and modifications in the expression of genes associated with resistance to β-lactams.
2023-03-31 | E-MTAB-12444 | biostudies-arrayexpress
Project description:The haploid and the heterozygous essential S.cerevisiae deletion pools were grown in the presence of compounds that we found to be synergistic with fluconazole. We also treated the deletion pools with combinations of those drugs and fluconazole to interrogate the mechanism of action of the drug interactions. These experimental samples were hybridized against DMSO or water control samples. The resulting hybridization pattern informs about sensitive and resistant yeast deletion mutants.
2011-09-07 | E-MTAB-394 | biostudies-arrayexpress
Project description:The 3q-syndrome is a well-known genetic condition caused by interstitial deletion in the long arm of chromosome 3. The phenotype of this syndrome is variable and the great variability in the extent of these deletions lead to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalance, patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. Here we report a prenatal diagnosis of a male fetus presenting ultrasounds evidence of corpus callosum dysplasia and ventriculomegaly showing a 3q13q21.2 deletion and a 12p13.33 microdeletion paternally inherited. Among several features previously attributed to the terminal deletion of 3q, corpus callosum dysplasia and ventriculomegaly has rarely been reported together. As the 12p13.33 microdeletion in the father was associated only to muscular hypotonia and joint laxity, involvement of terminal 12p deletions in fetus clinical features was not possible to verify in prenatal period. This report may provide a reference for prenatal diagnosis and genetic counseling in patients who have prenatal diagnosis of 3q13q21.2 deletions and 12p13.33 microdeletion.
2022-11-10 | E-MTAB-12413 | biostudies-arrayexpress
Project description:Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical insult and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p less than or = 0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-145]
2013-03-16 | E-BUGS-145 | biostudies-arrayexpress
Project description:PAX5, a transcription factor essential for B-cell development, has been found as a frequent target of abnormalities in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) cases, showing point mutations, deletions, as well as translocations with several partner genes. We identified four novel PAX5 fusion partner genes by performing a screening on BCP-ALL cases with 9p rearrangements. Copy Number Variation analysis of translocated samples showed that few significant cooperative genetic lesions are present in addition to the translocation event, suggesting that it might have a primary role in leukemogenesis.
2015-03-02 | E-MTAB-2416 | biostudies-arrayexpress
Project description:We isolated total RNA from staged embryos at 2 hour intervals over a 24 h period. Total RNA from 8 h embryos was used as a reference for the time course. This expression study used a >16,000 oligonucleotide (65-mers) probe set from Compugen to examine changes in gene expression in wild-type Danio rerio during development, emphasizing the period of segmentation, when the nervous system is forming. Embryos were provided by Scientific Hatcheries.
2005-01-01 | E-TIGR-17 | biostudies-arrayexpress
Project description:The effect of a year-long 10 reduction in water temperature on global gene expression in tail skeletal muscle from adult, male zebrafish was determined using a long oligonucleotide probe set (16,399 65mers from Compugen) spotted onto glass slides. Outbred male zebrafish were obtained from a commercial supplier (Liles Tropical Fish, FL) at 6 months of age. Fish were maintained at 28 until 10 months of age. (see Gerhard et al., Exp Gerontol 37,1055-68, 2002) For temperature reduction, water temperature was decreased by 2.5 per week for 4 weeks. Fish were maintained until 22 months of age. Fish were fed fish flakes (Wardely Corp. Secaucus, NJ) twice per day. Each feeding was a discrete event in which a small measured amount of granular food was sprinkled on the water surface. A second small aliquot was offered if the first has been eaten within a few minutes. The feeding stopped when food from the previous aliquot has not been eaten and feeding behavior has ceased. By providing a consecutive series of small aliquots until food is no longer accepted, every member of the tank has an opportunity to eat until satiety, yet the amount of uneaten food is minimized. At 22 months of age, fish were euthanized by decapitation. Total RNA was harvested from a pool of tail muscle samples from 5 fish. Two independent pools of 5 fish per pool were collected from fish maintained at 18 and 28. Flip-dye hybridizations were performed on each pool for a total of 4 hybridizations in this study. Experiments DAR011d0001 and DAR011d0002 are flip-dye hybridizations from Pool 1. Experiments DAR011d0003 and DAR011d004 are flip-dye hybridizations from Pool 2.
2005-01-01 | E-TIGR-19 | biostudies-arrayexpress
Project description:Genomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant?s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.
2007-02-24 | E-TABM-105 | biostudies-arrayexpress
Project description:The purpose of this study was to determine 1) the transcriptional program elicited by exposure to three estrogen receptor (ER) agonists: 17 a-ethynyl estradiol (EE), genistein (Ges) and bisphenol A (BPA) during fetal development of the rat testis and epididymis; and 2) whether very low dosages of estrogens (evaluated over five orders of magnitude of dosage) produce unexpected changes in gene expression (i.e., a non-monotonic dose-response curve). In three independently conducted experiments, Sprague-Dawley rats were dosed (s.c.) with 0.001-10mg EE/kg/day, 0.001-100 mg Ges/kg/day or 0.002-400mg BPA/kg/day. While morphological changes in the developing reproductive system were not observed, the gene expression profile of target tissues were modified in a dose-responsive manner. Independent dose-response analyses of the three studies identified 56 genes that are significantly modified by EE, 28 genes by Ges and 15 genes by BPA (out of 8740). Even more genes were observed to be significantly changed when only the high dose is compared with all lower doses: 141, 46 and 67 genes, respectively. Global analyses aimed at detecting genes consistently modified by all of the chemicals identified 52 genes whose expression changed in the same direction across the three chemicals. The dose-response curve for gene expression changes was monotonic for each chemical, with both the number of genes significantly changed and the magnitude of change, for each gene, decreasing with decreasing dose. Using the available annotation of the gene expression changes induced by ER-agonist, our data suggest that a variety of cellular pathways are affected by estrogen exposure. These results indicate that gene expression data are diagnostic of mode of action and, if they are evaluated in the context of traditional toxicological end-points, can be used to elucidate dose-response characteristics.
2005-05-18 | E-TABM-12 | biostudies-arrayexpress