Genomic medicine最新文献_第9页

Parallel analysis of tetramerization domain mutants of the human p53 protein using PCR colonies. 用PCR菌落平行分析人p53蛋白四聚域突变体。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-09-05 DOI: 10.1007/s11568-007-9011-8

Joshua Merritt, Kim G Roberts, James A Butz, Jeremy S Edwards

{"title":"Parallel analysis of tetramerization domain mutants of the human p53 protein using PCR colonies.","authors":"Joshua Merritt, Kim G Roberts, James A Butz, Jeremy S Edwards","doi":"10.1007/s11568-007-9011-8","DOIUrl":"https://doi.org/10.1007/s11568-007-9011-8","url":null,"abstract":"A highly-parallel yeast functional assay, capable of screening approximately 100-1,000 mutants in parallel and designed to screen the activity of transcription activator proteins, was utilized to functionally characterize tetramerization domain mutants of the human p53 transcription factor and tumor suppressor protein. A library containing each of the 19 possible single amino acid substitutions (57 mutants) at three positions in the tetramerization domain of the human p53 protein, was functionally screened in Saccharomyces cerevisiae. Amino acids Leu330 and Ile332, whose side chains form a portion of a hydrophobic pocket that stabilizes the active p53 tetramer, were found to tolerate most hydrophobic amino acid substitutions while hydrophilic substitutions resulted in the inactivation of the protein. Amino acid Gln331 tolerated essentially all mutations. Importantly, highly parallel mutagenesis and cloning techniques were utilized which, in conjunction with recently reported highly parallel DNA sequencing methods, would be capable of increasing throughput an additional 2-3 orders of magnitude.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 3-4","pages":"113-24"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-007-9011-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The geography of genetics: an analysis of referral patterns to a cancer genetics service. 遗传学地理学：癌症遗传学服务转诊模式分析。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2008-01-23 DOI: 10.1007/s11568-008-9016-y

Kevin McDonald, Rachel Iredale, Gary Higgs

{"title":"The geography of genetics: an analysis of referral patterns to a cancer genetics service.","authors":"Kevin McDonald, Rachel Iredale, Gary Higgs","doi":"10.1007/s11568-008-9016-y","DOIUrl":"10.1007/s11568-008-9016-y","url":null,"abstract":"This study uses a geographical information system (GIS) and statistical analysis to look for patterns in referrals to a British cancer genetics service. In this case, familial cancers are taken to be those that can develop when an individual inherits DNA mutations that cause an increased risk of cancer. Between 1998 and 2006 the Cancer Genetics Service for Wales received nearly 11,000 referrals for patients resident in Wales and it is the service database recording those referrals which is the subject of this secondary analysis. Using postcodes to match referred patients to areas, deprivation scores were assigned. Referral rates per 10,000 head of population across the 8-year study period by unitary authority are presented, as is information on referrals from primary and secondary care sources by year. Each patient referred has their family history of cancer recorded and is assigned to a risk category; high, medium or average. There are correlations between number of GPs (General Practitioners) in a practice, number of patients referred from a practice, and deprivation as measured by the overall Welsh Index of Multiple Deprivation 2005, such that the two former factors increase as deprivation decreases. Over time there were changes in referral sources, with referrals from primary care overtaking those from secondary care in percentage and absolute terms. There were also changes in the types of cancer referred, risk categories seen and to which centre referrals were made. Referral patterns reveal an inverse relationship between deprivation and health service availability and use.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 3-4","pages":"129-38"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2269036/pdf/11568_2008_Article_9016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region. RHOB基因的转录活性受其启动子区域的调控多态性的影响。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-11-20 DOI: 10.1007/s11568-007-9012-7

Sandra Mahr, Brigitte Müller-Hilke

引用次数: 4

5alpha-androstane-3alpha,17beta-diol selectively activates the canonical PI3K/AKT pathway: a bioinformatics-based evidence for androgen-activated cytoplasmic signaling. 5 α -雄烷-3 α，17 β -二醇选择性激活典型的PI3K/AKT通路:雄激素激活细胞质信号传导的生物信息学证据。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2008-02-27 DOI: 10.1007/s11568-008-9018-9

Mikhail G Dozmorov, Qing Yang, Adam Matwalli, Robert E Hurst, Daniel J Culkin, Bradley P Kropp, Hsueh-Kung Lin

{"title":"5alpha-androstane-3alpha,17beta-diol selectively activates the canonical PI3K/AKT pathway: a bioinformatics-based evidence for androgen-activated cytoplasmic signaling.","authors":"Mikhail G Dozmorov, Qing Yang, Adam Matwalli, Robert E Hurst, Daniel J Culkin, Bradley P Kropp, Hsueh-Kung Lin","doi":"10.1007/s11568-008-9018-9","DOIUrl":"https://doi.org/10.1007/s11568-008-9018-9","url":null,"abstract":"5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is reduced from the potent androgen, 5alpha-dihydrotestosterone (5alpha-DHT), by reductive 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs) in the prostate. 3alpha-diol is recognized as a weak androgen with low affinity toward the androgen receptor (AR), but can be oxidized back to 5alpha-DHT. However, 3alpha-diol may have potent effects by activating cytoplasmic signaling pathways, stimulating AR-independent prostate cell growth, and, more importantly, providing a key signal for androgen-independent prostate cancer progression. A cancer-specific, cDNA-based membrane array was used to determine 3alpha-diol-activated pathways in regulating prostate cancer cell survival and/or proliferation. Several canonical pathways appeared to be affected by 3alpha-diol-regulated responses in LNCaP cells; among them are apoptosis signaling, PI3K/AKT signaling, and death receptor signaling pathways. Biological analysis confirmed that 3alpha-diol stimulates AKT activation; and the AKT pathway can be activated independent of the classical AR signaling. These observations sustained our previous observations that 3alpha-diol continues to support prostate cell survival and proliferation regardless the status of the AR. We provided the first systems biology approach to demonstrate that 3alpha-diol-activated cytoplasmic signaling pathways are important components of androgen-activated biological functions in human prostate cells. Based on the observations that levels of reductive 3alpha-HSD expression are significantly elevated in localized and advanced prostate cancer, 3alpha-diol may, therefore, play a critical role for the transition from androgen-dependent to androgen-independent prostate cancer in the presence of androgen deprivation.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 3-4","pages":"139-46"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-008-9018-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Clinical improvement after treatment with VEGF(165) in patients with severe chronic lower limb ischaemia. VEGF治疗严重慢性下肢缺血后的临床改善(165)。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-05-25 DOI: 10.1007/s11568-007-9006-5

Andrei Anghel, Bogdan Mut-Vitcu, Lorand Savu, Catalin Marian, Edward Seclaman, Raluca Iman, Adriana-Maria Neghina, Stefan I Dragulescu

{"title":"Clinical improvement after treatment with VEGF(165) in patients with severe chronic lower limb ischaemia.","authors":"Andrei Anghel, Bogdan Mut-Vitcu, Lorand Savu, Catalin Marian, Edward Seclaman, Raluca Iman, Adriana-Maria Neghina, Stefan I Dragulescu","doi":"10.1007/s11568-007-9006-5","DOIUrl":"https://doi.org/10.1007/s11568-007-9006-5","url":null,"abstract":"The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia using a plasmid vector encoding the vascular endothelial growth factor (phVEGF(165)). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF ( 165 )isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection with 0.5 ml saline solution containing 10(11) copies of VEGF ( 165 ) plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 1-2","pages":"47-55"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-007-9006-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Mechanism of Alu integration into the human genome. Alu整合到人类基因组的机制。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-03-28 DOI: 10.1007/s11568-007-9002-9

Jian-Min Chen, Claude Férec, David N Cooper

{"title":"Mechanism of Alu integration into the human genome.","authors":"Jian-Min Chen, Claude Férec, David N Cooper","doi":"10.1007/s11568-007-9002-9","DOIUrl":"https://doi.org/10.1007/s11568-007-9002-9","url":null,"abstract":"LINE-1 or L1 has driven the generation of at least 10% of the human genome by mobilising Alu sequences. Although there is no doubt that Alu insertion is initiated by L1-dependent target site-primed reverse transcription, the mechanism by which the newly synthesised 3' end of a given Alu cDNA attaches to the target genomic DNA is less well understood. Intrigued by observations made on 28 pathological simple Alu insertions, we have sought to ascertain whether microhomologies could have played a role in the integration of shorter Alu sequences into the human genome. A meta-analysis of the 1624 Alu insertion polymorphisms deposited in the Database of Retrotransposon Insertion Polymorphisms in Humans (dbRIP), when considered together with a re-evaluation of the mechanism underlying how the three previously annotated large deletion-associated short pathological Alu inserts were generated, enabled us to present a unifying model for Alu insertion into the human genome. Since Alu elements are comparatively short, L1 RT is usually able to complete nascent Alu cDNA strand synthesis leading to the generation of full-length Alu inserts. However, the synthesis of the nascent Alu cDNA strand may be terminated prematurely if its 3' end anneals to the 3' terminal of the top strand's 5' overhang by means of microhomology-mediated mispairing, an event which would often lead to the formation of significantly truncated Alu inserts. Furthermore, the nascent Alu cDNA strand may be 'hijacked' to patch existing double strand breaks located in the top-strand's upstream regions, leading to the generation of large genomic deletions.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 1-2","pages":"9-17"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-007-9002-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Genomic medicine: a new frontier of medicine in the twenty first century. 基因组医学:21世纪医学的新前沿。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-04-24 DOI: 10.1007/s11568-007-9003-8

Dhavendra Kumar

引用次数: 18

Deciphering modular and dynamic behaviors of transcriptional networks. 解码转录网络的模块化和动态行为。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-05-11 DOI: 10.1007/s11568-007-9004-7

Ming Zhan

{"title":"Deciphering modular and dynamic behaviors of transcriptional networks.","authors":"Ming Zhan","doi":"10.1007/s11568-007-9004-7","DOIUrl":"https://doi.org/10.1007/s11568-007-9004-7","url":null,"abstract":"The coordinated and dynamic modulation or interaction of genes or proteins acts as an important mechanism used by a cell in functional regulation. Recent studies have shown that many transcriptional networks exhibit a scale-free topology and hierarchical modular architecture. It has also been shown that transcriptional networks or pathways are dynamic and behave only in certain ways and controlled manners in response to disease development, changing cellular conditions, and different environmental factors. Moreover, evolutionarily conserved and divergent transcriptional modules underline fundamental and species-specific molecular mechanisms controlling disease development or cellular phenotypes. Various computational algorithms have been developed to explore transcriptional networks and modules from gene expression data. In silico studies have also been made to mimic the dynamic behavior of regulatory networks, analyzing how disease or cellular phenotypes arise from the connectivity or networks of genes and their products. Here, we review the recent development in computational biology research on deciphering modular and dynamic behaviors of transcriptional networks, highlighting important findings. We also demonstrate how these computational algorithms can be applied in systems biology studies as on disease, stem cells, and drug discovery.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 1-2","pages":"19-28"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-007-9004-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom. 诊断特发性学习障碍:微阵列技术在英国国家卫生服务的成本效益分析。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-06-05 DOI: 10.1007/s11568-007-9005-6

Sarah Wordsworth, James Buchanan, Regina Regan, Val Davison, Kim Smith, Sara Dyer, Carolyn Campbell, Edward Blair, Eddy Maher, Jenny Taylor, Samantha J L Knight

{"title":"Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom.","authors":"Sarah Wordsworth, James Buchanan, Regina Regan, Val Davison, Kim Smith, Sara Dyer, Carolyn Campbell, Edward Blair, Eddy Maher, Jenny Taylor, Samantha J L Knight","doi":"10.1007/s11568-007-9005-6","DOIUrl":"https://doi.org/10.1007/s11568-007-9005-6","url":null,"abstract":"Array based comparative genomic hybridisation (aCGH) is a powerful technique for detecting clinically relevant genome imbalance and can offer 40 to > 1000 times the resolution of karyotyping. Indeed, idiopathic learning disability (ILD) studies suggest that a genome-wide aCGH approach makes 10-15% more diagnoses involving genome imbalance than karyotyping. Despite this, aCGH has yet to be implemented as a routine NHS service. One significant obstacle is the perception that the technology is prohibitively expensive for most standard NHS clinical cytogenetics laboratories. To address this, we investigated the cost-effectiveness of aCGH versus standard cytogenetic analysis for diagnosing idiopathic learning disability (ILD) in the NHS. Cost data from four participating genetics centres were collected and analysed. In a single test comparison, the average cost of aCGH was pound442 and the average cost of karyotyping was pound117 with array costs contributing most to the cost difference. This difference was not a key barrier when the context of follow up diagnostic tests was considered. Indeed, in a hypothetical cohort of 100 ILD children, aCGH was found to cost less per diagnosis ( pound3,118) than a karyotyping and multi-telomere FISH approach ( pound4,957). We conclude that testing for genomic imbalances in ILD using microarray technology is likely to be cost-effective because long-term savings can be made regardless of a positive (diagnosis) or negative result. Earlier diagnoses save costs of additional diagnostic tests. Negative results are cost-effective in minimising follow-up test choice. The use of aCGH in routine clinical practice warrants serious consideration by healthcare providers.","PeriodicalId":87975,"journal":{"name":"Genomic medicine","volume":"1 1-2","pages":"35-45"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11568-007-9005-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27794881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

Genome mirror-2007. 基因组的镜子- 2007。

Genomic medicine Pub Date : 2007-01-01 Epub Date: 2007-12-28 DOI: 10.1007/s11568-007-9014-5

Dhavendra Kumar

引用次数: 0