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In PTEN-deficient prostate and breast cancers, CHD1 depletion profoundly and specifically suppressed cell proliferation, cell survival and tumorigenic potential. conceived the original hypothesis of synthetic essentiality. Mechanistically, functional PTEN stimulates the GSK3β-mediated phosphorylation of CHD1 degron domains, which promotes CHD1 degradation via the β-Tr CP-mediated ubiquitination–proteasome pathway. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. We also posited that such synthetic-essential genes would be therapeutic targets in cancers that harbour specific tumour-suppressor deficiencies. In addition to known synthetic-lethal interactions, this approach uncovered the chromatin helicase DNA-binding factor CHD1 as a putative synthetic-essential gene in PTEN-deficient cancers. designed and performed cell-line-derived xenograft-model and signalling-pathway experiments.
Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. uses cookies to improve performance by remembering your session ID when you navigate from page to page. Please set your browser to accept cookies to continue.All things considered, to look at just a few markers across many, many individuals, PCR may be the best choice, says Marijo Gallina, marketing manager for genotyping at Affymetrix.A host of q PCR-based formats exist for genotyping small numbers of markers, with a variety of panels available from different vendors and contract-service providers, using Taq Man-type probes or SYBR-like chemistry, for example.Conversely, PTEN deficiency results in stabilization of CHD1, which in turn engages the trimethyl lysine-4 histone H3 modification to activate transcription of the pro-tumorigenic TNF–NF-κB gene network. This study identifies a novel PTEN pathway in cancer and provides a framework for the discovery of ‘trackable’ targets in cancers that harbour specific tumour-suppressor deficiencies. This cookie stores just a session ID; no other information is captured.Accepting the NEJM cookie is necessary to use the website.And in the case of diseases such as cancer, these can be used to track a tumor’s origin and descent.Although next-generation sequencing (NGS)—whether of the whole genome or a selection thereof—has become the go-to technique for much of contemporary genomics for the discovery of previously unknown alleles, this relatively data-intensive and costly technique has yet to surpass more tried and true genotyping technologies when it comes to genotyping large numbers of samples.Among the principal considerations when choosing a genotyping technology are the number of samples and the number (and type) of variables to be tested.In addition, the per-sample and per-datapoint costs, throughput, availability of equipment, bioinformatics and other required expertise, turnaround time and hands-on time influence the methodology selected.In the absence of a "gold standard"/"reference method" for the gene expression measurements, studies evaluating and comparing the performance of various microarray platforms have often yielded subjective and conflicting conclusions.To address this issue we have conducted a large scale Taq Man In this study, we analyzed the gene expression profiles of three human tissues: brain, lung, liver and one universal human reference sample (UHR) using two representative commercial long-oligonucleotide microarray platforms: (1) Applied Biosystems Human Genome Survey Microarrays (based on single-color detection); (2) Agilent Whole Human Genome Oligo Microarrays (based on two-color detection).
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