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Sample records for cdkn2b p15 gene

  1. Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B

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    López-Nevot Miguel

    2005-04-01

    Full Text Available Abstract Background The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines Methods We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP. Results The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5% melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2 and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2. One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation. No defects were found in the remaining genes. Conclusion These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied.

  2. Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

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    Sayed AbdulAzeez

    2016-03-01

    Full Text Available Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2. The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175 and a risk haplotype (TGGA p = 2.86 × 10 − 10 for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.

  3. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

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    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  4. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    International Nuclear Information System (INIS)

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis

  5. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.

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    Wrensch, Margaret; Jenkins, Robert B; Chang, Jeffrey S; Yeh, Ru-Fang; Xiao, Yuanyuan; Decker, Paul A; Ballman, Karla V; Berger, Mitchel; Buckner, Jan C; Chang, Susan; Giannini, Caterina; Halder, Chandralekha; Kollmeyer, Thomas M; Kosel, Matthew L; LaChance, Daniel H; McCoy, Lucie; O'Neill, Brian P; Patoka, Joe; Pico, Alexander R; Prados, Michael; Quesenberry, Charles; Rice, Terri; Rynearson, Amanda L; Smirnov, Ivan; Tihan, Tarik; Wiemels, Joe; Yang, Ping; Wiencke, John K

    2009-08-01

    The causes of glioblastoma and other gliomas remain obscure. To discover new candidate genes influencing glioma susceptibility, we conducted a principal component-adjusted genome-wide association study (GWAS) of 275,895 autosomal variants among 692 adult high-grade glioma cases (622 from the San Francisco Adult Glioma Study (AGS) and 70 from the Cancer Genome Atlas (TCGA)) and 3,992 controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)). For replication, we analyzed the 13 SNPs with P < 10(-6) using independent data from 176 high-grade glioma cases and 174 controls from the Mayo Clinic. On 9p21, rs1412829 near CDKN2B had discovery P = 3.4 x 10(-8), replication P = 0.0038 and combined P = 1.85 x 10(-10). On 20q13.3, rs6010620 intronic to RTEL1 had discovery P = 1.5 x 10(-7), replication P = 0.00035 and combined P = 3.40 x 10(-9). For both SNPs, the direction of association was the same in discovery and replication phases. PMID:19578366

  6. Genetic association of SNPs near ATOH7, CARD10, CDKN2B, CDC7 and SIX1/SIX6 with the endophenotypes of primary open angle glaucoma in Indian population.

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    Ferdinamarie Sharmila Philomenadin

    Full Text Available Primary open angle glaucoma (POAG belonging to a group of optic neuropathies, result from interaction between genetic and environmental factors. Study of associations with quantitative traits (QTs is one of the successful strategies to understand the complex genetics of POAG. The current study attempts to explore the association of variations near/in genes like ATOH7, SIX1/SIX6 complex, CDKN2B, CARD10, and CDC7 with POAG and its QTs including vertical cup to disc ratio (VCDR, central corneal thickness (CCT, intra ocular pressure (IOP, and axial length (AL. Case-control study design was carried out in a sample size of 97 POAG cases and 371 controls from South India. Model-based (additive, recessive, dominant association of the genotypes and their interaction was carried out between cases and controls using chi-square, linear and logistic regression methods. Nominal significance (P<0.05 was observed for QTs like i VCDR with SNPs rs1900004 (ATOH7; rs1192415 (CDC7; rs10483727 (SIX1/SIX6, rs9607469 (CARD10; ii CCT with rs1192415; iii IOP with rs1900004 and iv AL with rs1900004 and rs1063192 (CDKN2B. We were able to replicate previously known interactions between ATOH7-SIX6 and SIX6-CDKN2B along with few novel interactions between ATOH7-CDC7 and SIX6 with genes including CARD10 and CDC7. In summary, our results suggest that a probable interaction among the candidate genes for QTs, play a major role in determining the individual's susceptibility to POAG.

  7. DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  8. Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome.

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    Scarisbrick, Julia J; Woolford, Alison J; Calonje, Eduardo; Photiou, Andrew; Ferreira, Sylvia; Orchard, Guy; Russell-Jones, Robin; Whittaker, Sean J

    2002-03-01

    There are few data on the molecular pathogenesis of cutaneous T cell lymphomas. A recent allelotyping study by our group identified frequent allelic loss on 9p, 10q, and 17p including losses on 9p21 in 16% of patients with mycosis fungoides and 46% with Sezary syndrome. The P15 and P16 genes are intricately linked on 9p21 and can be inactivated in melanoma and non-Hodgkin's lymphoma. We have therefore studied 76 patients with either mycosis fungoides or Sezary syndrome for abnormalities of these genes. DNA samples were analyzed for loss of heterozygosity, homozygous deletion, intragenic mutations, and promoter methylation. In addition P15 and P16 protein expression was assessed. Microsatellite analysis was informative in 73 of 76 cases: allelic loss on 9p21 was identified in 18 patients (25%), including 12 of 57 with mycosis fungoides (21%) and six of 16 with Sezary syndrome (37%). Single strand conformation polymorphism analysis of the entire coding regions of both genes did not identify any mutations, although two polymorphisms were identified including C613A, which has not previously been described. P15 and P16 gene promoter methylation was found in 45% and 29% of patients, respectively. Furthermore aberrant P15 protein expression was detected in 85% of patients analyzed with P15 gene abnormalities and abnormal P16 expression in 59% with P16 gene abnormalities. These abnormalities were not dependent on cutaneous stage of disease. This study suggests that abnormalities of the P15 and P16 genes are common in both early and advanced stages of mycosis fungoides and Sezary syndrome and that these genes may be inactivated by allelic loss and aberrant promoter methylation.

  9. Clinicopathological significance and potential drug target of p15INK4B in multiple myeloma

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    Li J

    2014-10-01

    Full Text Available Jun Li,1,* Lintao Bi,1 Yumei Lin,1,* Zhenxia Lu,1 Gang Hou2 1Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: Multiple myeloma (MM is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. In addition to genetic changes, gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation in MM. The cyclin-dependent kinase inhibitor 1 (CDKN2B or p15INK4B gene lies adjacent to the tumor suppressor gene, cyclin-dependent kinase inhibitor 2 (CDKN2A, and is frequently mutated and deleted in a wide variety of tumors, including MM. However, there is a lack of systematic analysis of p15 epigenetic modification such as methylation in MM from different studies that can provide more powerful estimation of an effect. In this study, we have systematically reviewed the studies of p15INK4B promoter methylation in MM and quantified the association between p15INK4B promoter methylation and MM using meta-analysis methods. We observed that the frequency of p15INK4B methylation is significantly higher in MM patients than in normal healthy controls. The pooled odds ratio (OR from ten studies including 394 MM and 99 normal individuals is 0.08, while confidence interval (CI is 0.03–0.21 (P<0.00001. This indicates that p15INK4B inactivation through methylation plays an important role in the pathogenesis of MM. In addition, the frequency of p15INK4B methylation was significantly higher in patients with MM than in those with asymptomatic monoclonal gammopathy of undetermined significance. The pooled OR from four studies is 0.40, 95% CI =0.21–0.78 (P=0.007. These results suggest that

  10. CO-DELETION OF BOTH p15/p16 GENES CORRELATES WITH POOR PROGNOSIS NON-SMALL CELL LUNG CNACER

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    胡颖; 廖美琳; 丁嘉安; 周瑾; 许凯黎

    2002-01-01

    Objective: To investigate the relationship between co-deletion of p15/p16 genes and the prognostic significance in patients with non-small cell lung cancer (NSCLC). Methods: By using polymerase chain reaction (PCR), the loss of p15/pl6 genes was examined in DNA samples from 140 NSCLC patients. Results: The rate of co-deletion in adenocarcinoma was significantly higher than that in squamous cell carcinoma (P0.05). By a five years' follow-up survey, the survival rate of NSCLC patients with co-deletion of pl5/pl6 genes was obviously lower than that of patients without co-deletion (P<0.01). In the multivariate analysis, co-deletion of p15/p16 genes and TNM stages were identified as independent predictors for overall survival (P<0.01). Conclusion: Since the co-deletion of pl5/pl6 genes is significantly related to the prognosis of NSCLC patients, detecting co-deletion of both genes might be used as a potential marker for NSCLC prognosis.

  11. Influence of Decitabine on Demethylation of P15INK4B Gene and the Growth and Apoptosis of Burkitt Lymphoma Raji Cells

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    LIU Qiao

    2014-12-01

    Full Text Available Objective: To explore the methylation status of P15INK4B gene and the biochemical influence of decitabine on the demethylation of P15INK4B gene and the growth and apoptosis of Burkitt lymphoma Raji cells. Methods: Trypan blue was used to test the effects of different concentrations of decitabine on cell growth curve of Burkitt lymphoma Rajj cells. Cell apoptostic rate was detected by flow cytometry (FCM. The expression of P15INK4B gene was detected by reverse transcription-polymerase chain reaction (RT-PCR and the degree of methylation of P15INK4B gene by methylation-specific PCR (MSP. Results: Different concentrations of decitabine had an inhibiting effect on the proliferation of Raji cells, and promote the apoptosis of Raji cells. After 48-h treatment of decitabine, the mRNA expression of P15INK4B gene of Raji cells was up-regulated in a dose-dependent manner by inducing the demethylation of P15INK4B gene. . Conclusion: There exists hypermethylated P15INK4B gene in Burkitt lymphoma Raji cells which makes P15INK4B gene down-regulated. However, decitabine can up-regulate the mRNA expression of P15INK4B gene through inducing the demethylation of P15INK4B gene, thus inhibiting the proliferation of lymphoma Raji cells.

  12. DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERα-positive breast cancer cells

    NARCIS (Netherlands)

    M. Ansems (Marleen); J.N. Søndergaard (Jonas Nørskov); A.M. Sieuwerts (Anieta); M.W.G. Looman (Maaike W. G.); M. Smid (Marcel); A.M.A. de Graaf (Annemarie M. A.); V. de Weerd (Vanja); M. Zuidscherwoude (Malou); J.A. Foekens (John); J.W.M. Martens (John); G.J. Adema (Gosse J.)

    2015-01-01

    textabstractBreast cancer is one of the most common causes of cancer-related deaths in women. The estrogen receptor (ERα) is well known for having growth promoting effects in breast cancer. Recently, we have identified DC-SCRIPT (ZNF366) as a co-suppressor of ERα and as a strong and independent prog

  13. DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERalpha-positive breast cancer cells

    NARCIS (Netherlands)

    Ansems, M.; Sondergaard, J.N.; Sieuwerts, A.M.; Looman, M.W.G.; Smid, M.; Graaf, A.M.A. de; Weerd, V. de; Zuidscherwoude, M.; Foekens, J.A.; Martens, J.W.; Adema, G.J.

    2015-01-01

    Breast cancer is one of the most common causes of cancer-related deaths in women. The estrogen receptor (ERalpha) is well known for having growth promoting effects in breast cancer. Recently, we have identified DC-SCRIPT (ZNF366) as a co-suppressor of ERalpha and as a strong and independent prognost

  14. Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15. 3-11p15. 1 by fluorescence in situ hybridization

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    Taviaux, S.A.; Demaille, J.G. (CRBM-CNRS and U 249 INSERM, Montpellier (France))

    1993-01-01

    The cell cycle control genes are highly conserved during evolution since they play a key role in the regulation of cell division. We have localized CDC25C and WEE1 respectively at 5q31 and 11p15.3-11p15.1 using fluorescent in situ hybridization of cDNA probes on human chromosomes. This shows that genes acting through a regulatory phosphorylation cascade are not clustered on the same chromosome. Furthermore, they appear to map on chromosomal regions involved in tumorigenesis. The 5q23-q31 region of chromosome 5 is deleted in some hematologic disorders, and the p15 region of chromosome 11 is involved in development of embryonic tumors. 26 refs., 1 fig.

  15. Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin

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    Jiang Shaohong

    2010-11-01

    Full Text Available Abstract Background We have previously demonstrated that phenylhexyl isothiocyanate (PHI, a synthetic isothiocyanate, inhibits histone deacetylases and remodels chromatins to induce growth arrest in HL-60 myeloid leukemia cells in a concentration-dependent manner. Methods To investigate the effect of PHI, a novel histone deacetylases inhibitor (HDACi, on demethylation and activation of transcription of p15 in acute lymphoid leukemia cell line Molt-4, and to further decipher the potential mechanism of demethylation, DNA sequencing and modified methylation specific PCR (MSP were used to screen p15-M and p15-U mRNA after Molt-4 cells were treated with PHI, 5-Aza and TSA. DNA methyltransferase 1 (DNMT1, 3A (DNMT3A, 3B (DNMT3B and p15 mRNA were measured by RT-PCR. P15 protein, acetylated histone H3 and histone H4 were detected by Western Blot. Results The gene p15 in Molt-4 cells was hypermethylated and inactive. Hypermethylation of gene p15 was attenuated and p15 gene was activated de novo after 5 days exposure to PHI in a concentration-dependent manner. DNMT1 and DNMT3B were inhibited by PHI (P Conclusion PHI could induce both DNA demethylation and acetylated H3 and H4 accumulation in Molt-4 cells. Hypermethylation of gene p15 was reversed and p15 transcription could be reactivated de novo by PHI.

  16. A novel familial 11p15.4 microduplication associated with intellectual disability, dysmorphic features, and obesity with involvement of the ZNF214 gene.

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    Sofos, Elvera; Pescosolido, Matthew F; Quintos, Jose B; Abuelo, Dianne; Gunn, Shelly; Hovanes, Karine; Morrow, Eric M; Shur, Natasha

    2012-01-01

    We evaluated a patient with mild intellectual disability, obesity, overgrowth, and dysmorphic features. Array comparative genomic hybridization (aCGH) analysis showed a single copy number increase of a BAC clone in the 11p15.4 region. Oligonucleotide aCGH refined the duplication to approximately 2.29  megabases (Mb) in size. Testing the parents revealed that the father, who had learning disabilities and overgrowth, also had the 11p15.4 duplication, and the mother had a normal microarray. In addition, the patient's brother and grandmother all share clinical features with the proband and tested positive for the duplication. The duplicated region (Chr11:6,934,067-9,220,605) encompasses 29 genes, including the ZNF214 gene, which has been postulated to play a role in Beckwith-Wiedemann syndrome [Alders et al., 2000]. This three-generation pedigree outlines features of a novel microduplication syndrome.

  17. 小球隐孢子虫(Cryptosporidium parvum)P15基因的克隆和表达%Cloning and Expressing of the Gene Encoding P15 of Cryptosporidium parvum

    Institute of Scientific and Technical Information of China (English)

    张守发; 鞠玉琳; 贾洪林

    2005-01-01

    通过PCR扩增出小球隐孢子虫(Cryptosporidium parvum)P15基因片段.将该片段连接到克隆质粒载体pUC19的BamH I酶切位点上,并对其序列进行了测定.结果表明,该基因长度为479 bp,编码的表面蛋白由148个氨基酸残基组成.再将P15蛋白基因片段分别在大肠杆菌和哺乳动物细胞中表达,经SDS-PAGE分析和Western blot检测,结果表明,小球隐孢子虫P15蛋白基因在大肠杆菌内获得表达的融合蛋白相对分子质量为50 000;在哺乳动物细胞中,重组痘病毒表达的蛋白相对分子质量为18 000~22 000,与直接从自然感染牛小球隐孢子虫分离的P15蛋白的相对分子质量相似.

  18. Frequency of aberrant promoter methylation of p15INK4b and O6-methylguanine-DNA methyltransferase genes in b-cell non-Hodgkin lymphoma: A pilot study

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    Kraguljac-Kurtović Nada

    2010-01-01

    Full Text Available The methylation status of the target promoter sequences of p15INK4B (p15 and O6-methylguanine-DNA methyltransferase (MGMT genes was studied by methylation-specific PCR in 10 adult patients with de novo B-cell non- Hodgkin lymphoma (B-NHL. The aberrant hypermethylation of the p15 gene was more frequent (50% compared to the hypermethylation of the MGMT gene (30%, and was detected in different types of B-NHL in both genes. Hypermethylation of the MGMT gene occurred exclusively in association with the hypermethylation of the p15 gene. All lymphoma patients with hypermethylation of the p15 and/or MGMT genes had a higher clinical stage of the disease (IV - V. We show the association of anemia and/or thrombocytopenia with the hypermethylation of the p15 gene, ascribing the p15 gene as a potential prognostic marker in B-NHL. Comethylation of MGMT with the p15 gene represents a novel finding and presents both genes as candidates for future studies of the hypermethylation profiles of B-NHL.

  19. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

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    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers.

  20. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

    Science.gov (United States)

    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers. PMID:24837742

  1. Counting CAG repeats in the Huntington’s disease gene by restriction endonuclease EcoP15I cleavage

    OpenAIRE

    Moencke-Buchner, E.; Reich, S.; Muecke, M.; M. Reuter; Messer, W; Wanker, E E; Krueger, D.H.

    2002-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant inheritance. The disease is caused by a CAG trinucleotide repeat expansion located in the first exon of the HD gene. The CAG repeat is highly polymorphic and varies from 6 to 37 repeats on chromosomes of unaffected individuals and from more than 30 to 180 repeats on chromosomes of HD patients. In this study, we show that the number of CAG repeats in the HD gene can be determined by restriction of the...

  2. Paternal imprinting of the SLC22A1LS gene located in the human chromosome segment 11p15.5

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    Krishna Lingegowda

    2004-06-01

    Full Text Available Abstract Background Genomic imprinting is an epigenetic chromosomal modification in the gametes or zygotes that results in a non-random monoallelic expression of specific autosomal genes depending upon their parent of origin. Approximately 44 human genes have been reported to be imprinted. A majority of them are clustered, including some on chromosome segment 11p15.5. We report here the imprinting status of the SLC22A1LS gene from the human chromosome segment 11p15.5 Results In order to test for allele specific expression patterns, PCR primer sets from the SLC22A1LS gene were used to look for heterozygosity in DNA samples from 17 spontaneous abortuses using PCR-SSCP and DNA sequence analyses. cDNA samples from different tissues of spontaneous abortuses showing heterozygosity were subjected to PCR-SSCP analysis to determine the allele specific expression pattern. PCR-SSCP analysis revealed heterozygosity in two of the 17 abortuses examined. DNA sequence analysis showed that the heterozygosity is caused by a G>A change at nucleotide position 473 (c.473G>A in exon 4 of the SLC22A1LS gene. PCR-SSCP analysis suggested that this gene is paternally imprinted in five fetal tissues examined. Conclusions This study reports the imprinting status of the SLC22A1LS gene for the first time. The results suggest imprinting of the paternal allele of this gene in five fetal tissues: brain, liver, placenta, kidneys and lungs.

  3. 36. Study on p16INK4a and p15INK4b genes of human bronchial epithelial cells malignantly transformed by cyclophosphamide and thiotepa

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Transformed human bronchial epithelial cells BEAS-2B induced by CP and TEPA were used to study abnormity of the tumor suppressor genes p15INK4b and p16INK4a, through which we can provide clues for explanations of the molecular mechanism in carcinogenesis of human bronchial epithelial cells induced by CP and TEPA. Analysis of the genomic DNA from the transformed BEAS-CP, and BEAS-T cells using PCR amplification, singe strand conformation polymorphism(SSCP) and DNA sequencing

  4. 地西他滨对骨髓增生异常综合征患者血浆中P15基因启动子区域甲基化的影响%Changes of P15 gene promoter region methylation following decitabine treatment in the plasma of patients with myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    邓银芬; 张秀群; 张磊; 苏爱玲; 张学忠; 徐燕丽

    2013-01-01

    Objective:To detect the methylation status of P15 gene promoter region in the plasma of patients with myelodysplastic syndrome (MDS) ,and to investigate the demethylating effects of dicitabine. Method: Methyl-ation-specific PCR (MSP) was used to detect the methylation status of P15 gene promoter region in the plasma of 4 patients,among them.one newly diagnosed MDS,three progressed into acute leukemia, with myelodysplastic syndrome before and after treated with decitabine plus semis CAG therapy. Result; Four cases were found to have an increased methylation in the promoter region,after treated with decitabine plus semis CAG,3 cases were not found increased methylation. In 4 cases.2 cases gain clinical response.and the other 2 cases were useless. Conclusion:P15 gene hypermethylation is associated with MDS pathogenesis. Decitabine has demethylating effect on the plasma from MDS patients The methylation status of P15 gene may serve as an important molecular marker to provide evidence for MDS diagnosis and predict the prognosis.%目的:检测骨髓增生异常综合征(MDS)患者血浆中P15基因启动子区域甲基化状况及地西他滨对其甲基化的影响.方法:采用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)法检测1例初治的MDS患者、3例MDS转化而来的AML患者使用地西他滨序贯半量CA(方案治疗前后血浆中P15基因启动子区域CPG岛甲基化情况,并分析其临床疗效.结果:4例患者治疗前均有P15基因甲基化,治疗1疗程后有3例患者P15基因甲基化得到逆转,4例患者中有2例获得临床缓解,2例无效.结论:MDS的发生与P15基因甲基化相关,地西他滨对MDS患者血浆P15基因高甲基化具有明显的去甲基化作用.P15基因甲基化检测可能成为MDS辅助诊断和预后判断的分子标记.

  5. A balanced t(5;17 (p15;q22-23 in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

    Directory of Open Access Journals (Sweden)

    Wijers-Koster Pauline

    2009-11-01

    Full Text Available Abstract Background Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH. Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases. Results A balanced t(5;17(p15;q22-23 was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17 translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1 gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10 gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases. Conclusion We report a novel t(5;17(p15;q22-23 translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or

  6. 骨髓增生异常综合征P15INK4B基因甲基化及药物去甲基化作用%Methylation of P15INK4B Gene in Patients with Myelodysplastic Syndromes and Demethylating Effects of Drugs

    Institute of Scientific and Technical Information of China (English)

    叶雪石; 刘霆; 崔旭; 孟文彤; 席亚明

    2007-01-01

    目的 检测骨髓增生异常综合征(MDS)患者P15INK4B基因甲基化状况;探讨5-氮杂-2′-脱氧胞嘧啶(decitabine)和三氧化二砷(As2O3)对MDS患者细胞的去甲基化作用.方法 采用限制性内切酶联合PCR方法检测14例MDS患者P15INK4B基因甲基化,选择1例由MDS转化为急性白血病患者的外周血单个核细胞,分组分别加入decitabine和As2O3进行处理,分析甲基化程度变化情况.结论 低危组MDS患者(RCMD)均未发现P15INK4B基因甲基化,4例高危组MDS患者(RAEB)和4例 MDS-AL患者发现P15INK4B基因甲基化.经decitabine和As2O3处理后,MDS患者细胞的甲基化程度均降低50%左右.结论 MDS的发生与P15INK4B基因甲基化密切相关,decitabine和As2O3均对MDS患者细胞高度甲基化的P15INK4B基因具明显去甲基化作用.

  7. A Novel Cryptic Three-Way Translocation t(2;9;18)(p23.2;p21.3;q21.33) with Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Othman, Moneeb A K; Rincic, Martina; Melo, Joana B; Carreira, Isabel M; Alhourani, Eyad; Hunstig, Friederike; Glaser, Anita; Liehr, Thomas

    2014-01-01

    Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and high resolution array-comparative genomic hybridization (aCGH) were applied. Thus, cryptic chromosomal aberrations not observed before were detected: three chromosomes were involved in a cytogenetically balanced occurring translocation t(2;9;18)(p23.2;p21.3;q21.33). Besides a translocation t(10;14)(q24;q11) was identified, an aberration known to be common in T-ALL. Due to the three-way translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16, CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in 13q14 was deleted. This patient, considered to have a normal karyotype after low resolution banding cytogenetics, was treated according to general protocol of anticancer therapy (ALL-BFM 95).

  8. A Novel Cryptic Three-Way Translocation t(2;9;18(p23.2;p21.3;q21.33 with Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Moneeb A. K. Othman

    2014-01-01

    Full Text Available Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH, multiplex ligation-dependent probe amplification (MLPA and high resolution array-comparative genomic hybridization (aCGH were applied. Thus, cryptic chromosomal aberrations not observed before were detected: three chromosomes were involved in a cytogenetically balanced occurring translocation t(2;9;18(p23.2;p21.3;q21.33. Besides a translocation t(10;14(q24;q11 was identified, an aberration known to be common in T-ALL. Due to the three-way translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16, CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in 13q14 was deleted. This patient, considered to have a normal karyotype after low resolution banding cytogenetics, was treated according to general protocol of anticancer therapy (ALL-BFM 95.

  9. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels;

    2007-01-01

    Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1...

  10. Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes

    DEFF Research Database (Denmark)

    Kool, Jaap; Uren, Anthony G; Martins, Carla P;

    2010-01-01

    genetic context of predisposing germline and somatic mutations. We also found associations between these loci with gender, age of tumor onset, and lymphocyte lineage (B or T cell). Comparison of retroviral insertion sites with single nucleotide polymorphisms associated with chronic lymphocytic leukemia...... revealed a significant overlap between the datasets. Together, our findings highlight the importance of genetic context within large-scale mutation detection studies, and they show a novel use for insertional mutagenesis data in prioritizing disease-associated genes that emerge from genome-wide association...

  11. Clinicopathological significance of p15 promoter hypermethylation in multiple myeloma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wei B

    2016-07-01

    Full Text Available Bing Wei, Shuhua Yang, Bo Zhang, Yong Feng Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: Published studies reported that loss of function of the p15INK4B gene is caused by hypermethylation; however, whether or not the inactivation is associated with the incidence and clinical significance of multiple myeloma (MM remains unclear. In this study, we performed a meta-analysis to quantitatively determine the effects of p15 hypermethylation on the incidence of MM. The related research articles in English and Chinese languages were evaluated. The data were extracted and assessed independently. The pooled data were analyzed and odds ratios were calculated and summarized. Sixteen eligible studies were selected for final analysis. We demonstrated that p15 hypermethylation is significantly higher in MM than that in normal bone marrow, as well as monoclonal gammopathy of undetermined significance. However, aberrant p15 hypermethylation was not significantly higher in advanced MM than that in early-stage MM. The results of this study reveal that p15 hypermethylation is correlated with an increased risk in the progression of monoclonal gammopathy of undetermined significance to MM. p15 hypermethylation, which induces the loss of function of the p15 gene, plays a critical role in the early tumorigenesis of MM and serves as a reputable diagnostic marker and potential drug target. Keywords: p15INK4B, methylation, asymptomatic monoclonal gammopathy of undetermined significance, tumor suppressor gene, odds ratio, meta-analysis

  12. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Saunders, Edward J; Leongamornlert, Daniel A;

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that...

  13. Inactivation of p15INK4b in chronic arsenic poisoning cases

    Directory of Open Access Journals (Sweden)

    Aihua Zhang

    2014-01-01

    Full Text Available Arsenic exposure from burning high arsenic-containing coal has been associated with human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation or genetic modification might contribute to arsenic-induced carcinogenicity. This study aims to clarify the correlation between arsenic pollution and functional defect of p15INK4b gene in arsenic exposure residents from a region of Guizhou Province, China. To this end, 103 arsenic exposure residents and 105 control subjects were recruited in this study. The results showed that the exposure group exhibited higher levels of urinary and hair arsenic compared with the control group (55.28 vs 28.87 μg/L, 5.16 vs 1.36 μg/g. Subjects with higher arsenic concentrations are more likely to have p15INK4b methylation and gene deletion (χ2 = 4.28, P = 0.04 and χ2 = 4.31, P = 0.04. We also found that the degree of p15INK4b hypermethylation and gene deletion occurred at higher incidence in the poisoning cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin cancer group, and were significantly associated with the stage of skin lesions (χ2 = 12.82, P < 0.01 and χ2 = 7.835, P = 0.005. These observations indicate that inactivation of p15INK4b through genetic alteration or epigenetic modification is a common event that is associated with arsenic exposure and the development of arsenicosis.

  14. TGFbeta influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b

    DEFF Research Database (Denmark)

    Seoane, J; Pouponnot, C; Staller, P;

    2001-01-01

    Transforming growth factor-beta (TGFbeta) is a cytokine that arrests epithelial cell division by switching off the proto-oncogene c-myc and rapidly switching on cyclin-dependent kinase (CDK) inhibitors such as p15INK4b. Gene responses to TGFbeta involve Smad transcription factors that are directly...... activated by the TGFbeta receptor. Why downregulation of c-myc expression by TGFbeta is required for rapid activation of p15INK4b has remained unknown. Here we provide evidence that TGFbeta signalling prevents recruitment of Myc to the p15INK4b transcriptional initiator by Myc-interacting zinc......-finger protein 1 (Miz-1). This relieves repression and enables transcriptional activation by a TGFbeta-induced Smad protein complex that recognizes an upstream p15INK4b promoter region and contacts Miz-1. Thus, two separate TGFbeta-dependent inputs - Smad-mediated transactivation and relief of repression by Myc...

  15. A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter

    Energy Technology Data Exchange (ETDEWEB)

    Krakowiak, P.A.; O`Quinn, J.R.; Watkins, W.S. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States)] [and others

    1997-02-01

    Distal arthrogryposis type 1 (DA1) and Freeman-Sheldon syndrome (FSS) are the two most common known causes of inherited multiple congenital contractures. We recently have characterized a new disorder (DA213) with a phenotype intermediate between DA1 and FSS. We report the mapping of a gene that causes DA213 to chromosome 11p15.5-pter. Linkage analysis in a single kindred generated a positive LOD score of 5.31 at {theta} = 0 with the marker D11S922, and recombinants localize the gene to an {approximately}3.5-6.5-cM region between the marker TH and the telomere. Analysis of additional families improves the LOD score to 6.45 at {theta} = 0 and suggests linkage homogeneity for DA213. 24 refs., 4 figs., 2 tabs.

  16. P04.23PROMOTOR HYPERMETHYLATION OF MGMT, P15, P16 AND RB1 IN PILOCYTIC ASTROCYTOMA

    Science.gov (United States)

    Sippl, C.; Urbschat, S.; Kim, Y.J.; Oertel, J.; Ketter, R.

    2014-01-01

    OBJECTIVE: Pilocytic astrocytomas are WHO grade I gliomas occurring mainly in the childhood and adolescent ages. Promoter hypermethylation of tumor suppressor genes is a very common mechanism in CNS neoplasias which is generally associated with their transcriptional silencing. MATERIAL & METHODS: Using MS-PCR, we analyzed the methylation status of the tumor suppressor genes p15, p16, RB1, and MGMT in n = 18 pilocytic astrocytomas. Furthermore, all tumour samples were tested for the R132H mutation of the IDH1 gene by use of immunohistochemical staining. The results of the MGMT methylation analysis were correlated with the individual clinical and demographical data as well as with the progression-free (PFS) and overall survival (OS). RESULTS: Each of the 18 pilocytic astrocytoma specimen presented unmethylated in the investigated promoter regions of p16 and RB1. For the p15 gene, 1/18 tumor sample showed a positive methylation signal (5.6%). This single case presented with an extraordinary aggressive clinical course including frequent local recurrences with meningeal metastases but without tumor upgrading. For the MGMT gene, however, methylation frequency was 44.5% (8/18). Interestingly, when stratified for the MGMT methylation status, the group of methylated pilocytic astrocytomas showed a significantly shortened PFS in the Kaplan-Meier curve compared to their unmethylated counterparts (11.75 Months vs. 74.0 Months; p = 0.041; univariate log rank test). CONCLUSION: Epigenetic mechanisms, in particular the promoter methylation of the MGMT and p15 genes, contrary to the perception of literatur that pilocytic astrocytomas are commonly unmethylated, may obviously have an impact on the clinical course in pilocytic astrocytoma disease.

  17. Clinical and molecular characterization of two patients with overlapping de novo microdeletions in 2p14-p15 and mild mental retardation

    DEFF Research Database (Denmark)

    Wohlleber, Eva; Kirchhoff, Eva Maria; Zink, Alexander M;

    2011-01-01

    microcephaly. In patient 1, molecular karyotyping detected a 2.23-Mb deletion in chromosome 2p14-p15 including 11 known genes. The second patient, with a 2.84-Mb microdeletion containing 15 genes, was identified in the DECIPHER database. The two deleted regions overlap by a stretch of 1.6 Mb that contains 10...

  18. Radiative p 15N Capture in the Region of Astrophysical Energies

    Science.gov (United States)

    Dubovichenko, S. B.; Burtebaev, N.; Dzhazairov-Kakhramanov, A. V.; Alimov, D. K.

    2016-06-01

    Within the framework of the modified potential cluster model with classification of orbital states according to the Young schemes, the possibility of describing experimental data for the astrophysical S-factor of p 15N radiative capture at energies from 50 to 1500 keV is considered. It is shown that on the basis of M1 and E1 transitions from various p 15N scattering states to the ground state of the 16O nucleus in the p 15N channel it is entirely possible to successfully explain the overall behavior of the S-factor in the considered energy region in the presence of two resonances.

  19. Cleft Lip/Palate, Short Stature, and Developmental Delay in a Boy with a 5.6-Mb Interstitial Deletion Involving 10p15.3p14

    Science.gov (United States)

    Gamba, Bruno F.; Rosenberg, Carla; Costa, Silvia; Richieri-Costa, Antonio; Ribeiro-Bicudo, Lucilene A.

    2015-01-01

    The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has been implicated in a few well-known human phenotypes, namely HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2 (DiGeorge syndrome 2), but a number of variable phenotypes have also been reported. Cleft lip/palate seems to be a very unusual finding within the clinical spectrum of patients with this deletion. Here, we report a male child born with short stature, cleft lip/palate, and feeding problems who was found to have a 5.6-Mb deletion at 10p15.3p14. PMID:25852446

  20. Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions.

    Science.gov (United States)

    Ishida, Yasuko; McCallister, Chelsea; Nikolaidis, Nikolas; Tsangaras, Kyriakos; Helgen, Kristofer M; Greenwood, Alex D; Roca, Alfred L

    2015-01-15

    The koala retrovirus (KoRV), which is transitioning from an exogenous to an endogenous form, has been associated with high mortality in koalas. For other retroviruses, the envelope protein p15E has been considered a candidate for vaccine development. We therefore examined proviral sequence variation of KoRV p15E in a captive Queensland and three wild southern Australian koalas. We generated 163 sequences with intact open reading frames, which grouped into 39 distinct haplotypes. Sixteen distinct haplotypes comprising 139 of the sequences (85%) coded for the same polypeptide. Among the remaining 23 haplotypes, 22 were detected only once among the sequences, and each had 1 or 2 non-synonymous differences from the majority sequence. Several analyses suggested that p15E was under purifying selection. Important epitopes and domains were highly conserved across the p15E sequences and in previously reported exogenous KoRVs. Overall, these results support the potential use of p15E for KoRV vaccine development.

  1. Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model.

    Science.gov (United States)

    Sherman, Blake P; Lindley, Emily M; Turner, A Simon; Seim, Howard B; Benedict, James; Burger, Evalina L; Patel, Vikas V

    2010-12-01

    A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.

  2. Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

    OpenAIRE

    Sherman, Blake P.; Lindley, Emily M.; Turner, A. Simon; Seim III, Howard B.; Benedict, James; Burger, Evalina L; Patel, Vikas V.

    2010-01-01

    A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and sub...

  3. Association of low p16INK4a and p15INK4b mRNAs expression with their CpG islands methylation with human hepatocellular carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Yang Qin; Jian-Yu Liu; Bo Li; Zhi-Lin Sun; Ze-Fang Sun

    2004-01-01

    AIM: To study the significance of p16 and p15 transcription suppression with hypermethylation of their genes′ 5′CpG islands during human hepatocellular carcinogenesis.METHODS: The mRNA expression levels of p16 and p15genes were evaluated in cancerous, para-cancerous and noncancerous tissues of 20 HCC, 3 normal liver tissues from 3accidentally died healthy adults using semi-quantitatively Northern blot. The methylation status was also assessed with methylation specific PCR.RESULTS: p16 mRNA expression level was decreased in the cancerous tissues in 60% (12/20) of HCC patients, of which 2 cases had no p16 mRNA detected, 5 cases (25%)displayed variation in the order of cancerous<paracancerous<non-cancerous liver tissues. p15 mRNA expression level was decreased in the cancerous tissues in 50% (10/20)HCC patients, of which one case had no p15 mRNA detected,4 cases (20%) displayed variation in the order of cancerous <para-cancerous<non-cancerous liver tissues. In cancerous,para-cancerous and non-cancerous tissues, p16 promoter CpG islands hypermethylation occurred 65%, 60% and 35%, while p15 promoter CpG islands hypermethylation occurred 50%, 40% and 25%. Of 12 HCCs with lower p16mRNA expression level, 11 cases showed p16 promoter CpG islands methylation (91.6%). Hundred percent (10/10)HCCs with lower p15 mRNA expression level showed p15promoter CpG islands methylation. Significant correlation between 5′CpG islands methylation and p16/p15 mRNA expression suppression was found. The decreased expression of p16/p15 mRNA or methylation of p16/p15 promoters 5′CpG island was significantly correlate with poor differentiation of HCC (P=0.0083, 0.0102, 0.00271, 0.0218,respectively, P<0.05).CONCLUSION: p16 and p15 genes transcriptional inactivation might play an important role in hepatocarcinogenesis. 5′CpG islands methylation might be the major mechanism of p16 and p15 genes inactivation in primary HCC in the studied population. 5′CpG islands methylation of

  4. Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Li, Huibo; Kong, Xiaolin; Cui, Gang; Ren, Cuicui; Fan, Shengjin; Sun, Lili; Zhang, Yingjie; Cao, Rongyi; Li, Yinghua; Zhou, Jin

    2015-11-01

    The aim of the present study was to investigate the effects of rapamycin and its underlying mechanisms on acute lymphoblastic leukemia (ALL) cells. We found that the p14, p15, and p57 genes were not expressed in ALL cell lines (Molt-4 and Nalm-6) and adult ALL patients, whereas mTOR, 4E-BP1, and p70S6K were highly expressed. In Molt-4 and Nalm-6 cells exposed to rapamycin, cell viability decreased and the cell cycle was arrested at the G1/S phase. Rapamycin restored p14, p15, and p57 gene expression through demethylation of the promoters of these genes. As expected, rapamycin also increased p14 and p15 protein expression in both Molt-4 and Nalm-6 cells, as well as p57 protein expression in Nalm-6 cells. Rapamycin additionally decreased mTOR and p70S6K mRNA levels, as well as p70S6K and p-p70S6K protein levels. However, depletion of mTOR by siRNA did not alter the expression and promoter methylation states of p14, p15, and p57. These results indicate that the inhibitory effect of rapamycin may be due mainly to increased p14, p15, and p57 expression via promoter demethylation and decreased mTOR and p70S6K expression in ALL cell lines. These results suggest a potential role for rapamycin in the treatment of adult ALL.

  5. Repression of p15INK4b expression by Myc through association with Miz-1

    DEFF Research Database (Denmark)

    Staller, P; Peukert, K; Kiermaier, A;

    2001-01-01

    Deregulated expression of c-myc can induce cell proliferation in established cell lines and in primary mouse embryonic fibroblasts (MEFs), through a combination of both transcriptional activation and repression by Myc. Here we show that a Myc-associated transcription factor, Miz-1, arrests cells ...... p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization....

  6. Maro Reef Site P15 9/21/2002 38-39M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Onemetersquare 1 meter x 1 meter benthic substrate at Maro Reef, site P15 25.446 N, 170.633 W, between 38 and 39 meters along a permanent transect.

  7. Leakage of Oil Following Rupture of Pipeline P/15-4 to Hook of Holland

    NARCIS (Netherlands)

    Kranenburg, C.

    1983-01-01

    This report presents computational results concerning the buoyancy-driven leakage of oil resulting from a possible rupture of the planned pipeline P/15-4 to Hook of Holland. The computations were commissioned by R.J. Brown and Associates (Netherlands) b.v. (RJBA Job No. 7004.02). The specifications

  8. Maro Reef Site P15 9/21/2002 49-50M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Maro Reef, site P15 (25.446 N, 170.633 W), between 49 and 50 meters along a permanent transect.

  9. Maro Reef Site P15 9/21/2002 40-41M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Maro Reef, site P15 (25.446 N, 170.633 W), between 40 and 41 meters along a permanent transect.

  10. Maro Reef Site P15 9/21/2002 43-44M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Maro Reef, site P15 (25.446 N, 170.633 W), between 43 and 44 meters along a permanent transect.

  11. Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA

    Science.gov (United States)

    Boros, Gábor; Miko, Edit; Muramatsu, Hiromi; Weissman, Drew; Emri, Eszter; van der Horst, Gijsbertus T. J.; Szegedi, Andrea; Horkay, Irén; Emri, Gabriella; Karikó, Katalin; Remenyik, Éva

    2015-01-01

    Major biological effects of UVB are attributed to cyclobutane pyrimidine dimers (CPDs), the most common photolesions formed on DNA. To investigate the contribution of CPDs to UVB-induced changes of gene expression, a model system was established by transfecting keratinocytes with pseudouridine-modified mRNA (Ψ-mRNA) encoding CPD-photolyase. Microarray analyses of this model system demonstrated that more than 50% of the gene expression altered by UVB was mediated by CPD photolesions. Functional classification of the gene targets revealed strong effects of CPDs on the regulation of the cell cycle and transcriptional machineries. To confirm the microarray data, cell cycle-regulatory genes, CCNE1 and CDKN2B that were induced exclusively by CPDs were selected for further investigation. Following UVB irradiation, expression of these genes increased significantly at both mRNA and protein levels, but not in cells transfected with CPD-photolyase Ψ-mRNA and exposed to photoreactivating light. Treatment of cells with inhibitors of c-Jun N-terminal kinase (JNK) blocked the UVB-dependent upregulation of both genes suggesting a role for JNK in relaying the signal of UVB-induced CPDs into transcriptional responses. Thus, photolyase mRNA-based experimental platform demonstrates CPD-dependent and -independent events of UVB-induced cellular responses, and, as such, has the potential to identify novel molecular targets for treatment of UVB-mediated skin diseases. PMID:26121660

  12. Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA.

    Directory of Open Access Journals (Sweden)

    Gábor Boros

    Full Text Available Major biological effects of UVB are attributed to cyclobutane pyrimidine dimers (CPDs, the most common photolesions formed on DNA. To investigate the contribution of CPDs to UVB-induced changes of gene expression, a model system was established by transfecting keratinocytes with pseudouridine-modified mRNA (Ψ-mRNA encoding CPD-photolyase. Microarray analyses of this model system demonstrated that more than 50% of the gene expression altered by UVB was mediated by CPD photolesions. Functional classification of the gene targets revealed strong effects of CPDs on the regulation of the cell cycle and transcriptional machineries. To confirm the microarray data, cell cycle-regulatory genes, CCNE1 and CDKN2B that were induced exclusively by CPDs were selected for further investigation. Following UVB irradiation, expression of these genes increased significantly at both mRNA and protein levels, but not in cells transfected with CPD-photolyase Ψ-mRNA and exposed to photoreactivating light. Treatment of cells with inhibitors of c-Jun N-terminal kinase (JNK blocked the UVB-dependent upregulation of both genes suggesting a role for JNK in relaying the signal of UVB-induced CPDs into transcriptional responses. Thus, photolyase mRNA-based experimental platform demonstrates CPD-dependent and -independent events of UVB-induced cellular responses, and, as such, has the potential to identify novel molecular targets for treatment of UVB-mediated skin diseases.

  13. Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.

    Directory of Open Access Journals (Sweden)

    Lasse Folkersen

    Full Text Available BACKGROUND: Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not fully understood. We investigated five different expression microarray datasets in order to determine if the genotype had effect on expression of any gene transcript in aorta, mammary artery, carotid plaque and lymphoblastoid cells. METHODOLOGY/PRINCIPAL FINDINGS: After multiple testing correction, no genes were found to have relation to the rs2891168 risk genotype, either on a genome-wide scale or on a regional (8 MB scale. The neighbouring ANRIL gene was found to have eight novel transcript variants not previously known from literature and these varied by tissue type. We therefore performed a detailed probe-level analysis and found small stretches of significant relation to genotype but no consistent associations. In all investigated tissues we found an inverse correlation between ANRIL and the MTAP gene and a positive correlation between ANRIL and CDKN2A and CDKN2B. CONCLUSIONS/SIGNIFICANCE: Investigation of relation of the risk genotype to gene expression is complicated by the transcript complexity of the locus. With our investigation of a range of relevant tissue we wish to underscore the need for careful attention to the complexity of the alternative splicing issues in the region and its implications to the design of future gene expression studies.

  14. A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y.; Liu, L.; Hao, M.W.; Liu, Q.; Chen, R.A.; Liang, Y.M. [Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi' an (China)

    2014-10-14

    p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

  15. Effects of common germ-line genetic variation in cell cycle genes on ovarian cancer survival

    DEFF Research Database (Denmark)

    Song, H.; Hogdall, E.; Ramus, S.J.;

    2008-01-01

    plausibly influence clinical characteristics of multiple tumors types. EXPERIMENTAL DESIGN: We examined associations between common germ-line genetic variation in 14 genes involved in cell cycle pathway (CCND1, CCND2, CCND3, CCNE1, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDK2, CDK4, CDK6, and RB1.......05) in these genes. The genotypes of each polymorphism were tested for association with survival by Cox regression analysis. RESULTS: A nominally statistically significant association between genotype and ovarian cancer survival was observed for polymorphisms in CCND2 and CCNE1. The per-allele hazard ratios (95......% confidence intervals) were 1.16 (1.03-1.31; P = 0.02) for rs3217933, 1.14 (1.02-1.27; P = 0.024) for rs3217901, and 0.85 (0.73-1.00; P = 0.043) for rs3217862 in CCND2 and 1.39 (1.04-1.85; P = 0.033) for rs3218038 in CCNE1. However, these were not significant after adjusting for multiple hypothesis tests...

  16. Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

    OpenAIRE

    Rasmus Hestehave Pedersen; Marina Rasmussen; Søren Overgaard; Ming Ding

    2015-01-01

    This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of pro...

  17. Leakage of Oil Following Rupture of Pipeline P/15-4 to Hook of Holland

    OpenAIRE

    Kranenburg, C.

    1983-01-01

    This report presents computational results concerning the buoyancy-driven leakage of oil resulting from a possible rupture of the planned pipeline P/15-4 to Hook of Holland. The computations were commissioned by R.J. Brown and Associates (Netherlands) b.v. (RJBA Job No. 7004.02). The specifications of the pipeline and oil as made available by RJBA are listed in Table 1. Assumed properties of seawater are also listed. Leak volumes up to 400 m were calculated as functions of time after rupture ...

  18. Impact of lead ions on biosynthetic capacity of Streptomyces recifensis var. lyticus 2p-15 strain

    Directory of Open Access Journals (Sweden)

    Т. P. Kilochok

    2006-01-01

    Full Text Available The influence of different concentrations of Pb ions on biosynthetical ability of Streptomyces recifensis var. lyticus 2P-15, which is the producer of compound complex of extracellular enzymes and growth stimulators, was studied. It has been showed, that Pb ions introduced in agar medium have had a stimulative effect on production of surface and depth mycelia. The Pb ions, which have been inoculated into liquid fermentative medium in concentration of 1,0–2,0 mg/l realized directed synthesis of bacterio- and proteolytic enzymes, had an influence on qualitative and quantitative composition of produced enzymes.

  19. Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair

    DEFF Research Database (Denmark)

    De Biasio, Alfredo; de Opakua, Alain Ibáñez; Mortuza, Gulnahar B;

    2015-01-01

    The intrinsically disordered protein p15(PAF) regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15(PAF)-PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP...

  20. The genetics of POAG in black South Africans: a candidate gene association study.

    Science.gov (United States)

    Williams, Susan E I; Carmichael, Trevor R; Allingham, R Rand; Hauser, Michael; Ramsay, Michele

    2015-01-01

    Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition. PMID:25669751

  1. Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair

    Science.gov (United States)

    de Biasio, Alfredo; de Opakua, Alain Ibáñez; Mortuza, Gulnahar B.; Molina, Rafael; Cordeiro, Tiago N.; Castillo, Francisco; Villate, Maider; Merino, Nekane; Delgado, Sandra; Gil-Cartón, David; Luque, Irene; Diercks, Tammo; Bernadó, Pau; Montoya, Guillermo; Blanco, Francisco J.

    2015-03-01

    The intrinsically disordered protein p15PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15PAF-PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP-box) of p15PAF tightly bound to the front-face of PCNA. In contrast to other PCNA-interacting proteins, p15PAF also contacts the inside of, and passes through, the PCNA ring. The disordered p15PAF termini emerge at opposite faces of the ring, but remain protected from 20S proteasomal degradation. Both free and PCNA-bound p15PAF binds DNA mainly through its histone-like N-terminal tail, while PCNA does not, and a model of the ternary complex with DNA inside the PCNA ring is consistent with electron micrographs. We propose that p15PAF acts as a flexible drag that regulates PCNA sliding along the DNA and facilitates the switch from replicative to translesion synthesis polymerase binding.

  2. Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats.

    Science.gov (United States)

    Hestehave Pedersen, Rasmus; Rasmussen, Marina; Overgaard, Søren; Ding, Ming

    2015-01-01

    This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats. PMID:26509146

  3. Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

    Directory of Open Access Journals (Sweden)

    Rasmus Hestehave Pedersen

    2015-01-01

    Full Text Available This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15 on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats.

  4. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    DEFF Research Database (Denmark)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng;

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may pl...

  5. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively. Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb. Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

  6. Expressions of p16, p15 and pRb in Cutaneous Squamous Cell Carcinomas%p16,p15及Rb蛋白在皮肤鳞状细胞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    武钦学; 吴志华; 唐慰萍

    2004-01-01

    目的:检测p16,p15及pRb在皮肤鳞癌中的表达及相互关系,探讨它们在皮肤鳞癌发生、发展中的作用.方法:用S-P免疫组化染色法检测48例皮肤鳞癌和10例正常皮肤中p16,p15蛋白及pRb的表达.结果:p16,p15及pRb在皮肤鳞癌中均有不同程度失表达,分别为16/48(33.3%),7/48(14.6%)及8/48(16.7%).而在正常表皮均呈阳性表达:不同分化皮肤鳞癌中,p16,p15的失表达在低分化鳞癌中显著高于高中分化鳞癌(P<0.05),pRb表达无显著性差异.结论:p16,p15及/或pRb的表达异常可能与皮肤鳞癌的发生、发展有关.

  7. p16,p15及pRb在表皮肿瘤中的表达%Expressions of p16,p15 and pRb in Neoplasms of Epidermis

    Institute of Scientific and Technical Information of China (English)

    武钦学; 吴志华; 唐慰萍

    2004-01-01

    目的检测p16、p15及pRb在表皮肿瘤(基底细胞癌,角化棘皮瘤,脂溢性角化病等)中的表达及相互关系,以探讨它们在表皮肿瘤中发生、发展中的作用.方法用S-P免疫组化染色法检测34例基底细胞癌(BCC),12例角化棘皮瘤(KA),11例脂溢性角化病及10例正常皮肤中p16,p15及pRb蛋白的表达.结果p16、p15及pRb在基底细胞癌中均有不同程度失表达,分别为11/34(32.4%),15/34(44.1%)及10/34(29.4%):除1例脂溢性角化病pRb蛋白阴性表达外,12例角化棘皮瘤,11例脂溢性角化病及10例正常皮肤中p16、p15及pRb蛋白均呈阳性表达;基底细胞癌中,部分肿瘤p16,p15的表达与pRb蛋白的表达呈负相关,即一方的表达伴另一方的不表达.结论p16、p15及/或pRb的表达异常可能与基底细胞癌的发生、发展有关;但与表皮良性肿瘤的发生无关.

  8. THE EXPRESSIONS AND SIGNIFICANCES OF p15,p16 AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN GASTRIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    王天宝; 高鹏; 曲延刚; 陈咸增; 李兆亭

    2000-01-01

    Objective:To investigate the relationships between the expressions of p15,p16 and vascular endothelial growth factor (VEGF) and gastric carcinoma(GC).Methods: Using immunohistochemical staining to examine the expressions of p15, p16and VEGF in archival wax-embedded specimens of 80 GC and 20 gastric benign disease(GBD). Results: The positive expression rate (PER) of p15 was significantly lower in GC than in GBD (43.75% VS. 69.23%, P<0.05). No relationship was found between PER of p15 and clinicopathologic factors. PER of p16 was 20% in GC, 55% in GBD (P<0.01).PER of p16 wasn't significantly different in gross types, histological types, with or without distant metastasis and pTNM stages. PER of p16 was 71.43% in invasive mucosa or suomucosa group, 17. 24% in invasive muscle group and 13. 64% in invoive serosa group (P<0.01); 12.96% in GC with lymph nodes metastasis, 34.62% in GC without lymph node metastasis (P<0.05). PER of VEGF in GC was 75. 00%, in GBD 7.69% (P<0. 001), in ulcerative type of GC and infiltrating type of GC were 81.97% and 40. 00%, respectively (P <0.05), in GC of invasive serosa was 95.45%, in GC of invasive muscle 51.72%(P<0.001), in GC of invasive mucosa or sulomucosa 42.86% (P<0.001). PER of VEGF in GC with lymph node metastasis was 82. 8%, without lymph node metastasis 54. 6%(P<0.05), in GC accompanied with distant metastasis was 100%, in GC without distant metastasis71.1% (P<0.05). PER of VEGF in pTNM Ⅰ and Ⅱ was 53.13%, in Ⅲ and IV 89.56% (P<0. 001). The expression of p15 correlated significantly With that of VEGF (P<0.001) and with that of p16 (P<0.01) in GC. Conclusion: p15 expression down-regulation has relationship with GC, but on relationship with the progress. p16 expression downregulation and VEGF expression up-regulation show significant relationships with clinicopathologic factors. There are significant relations between p15 and p16 negative expressionsand between p15 expression down-regulation and VEGF expression up-regulation.

  9. Effect of P15INK4b/MTS2 on the proliferation of human hepatoma cells SMMC-7721

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The full length cDNA coding for P15 INK4b, which is a cyclin-dependent kinase inhibitor, was cloned to plasmid PXJ41-neo (Eco RⅠ/XhoⅠ site) and the new constructed plasmid pXJp15 was obtained. pXJp15 was transferred into the human hepatoma SMMC-7721 cells by lipofectine reagent. After G418 selection, a series of cell lines stably expressing high levels of P15 (named SHT) and the clone containing vector PXJ41-neo only (named SVXJ) were obtained by Northern and Western analysis. The results showed that the proliferation of SHT cells is inhibited compared with that of SVXJ cells. Cell cycle analysis indicated that overexpressing of P15 inhibited the growth of SHT cells by decreasing progrssion of cells from G1 to S and G2 to M phases. The levels of c-Myc and c-Fos were obviously decreased in SHT cells compared with control cells by Western blotting. The decreased expression of oncogene may be one of the molecular mechanisms of the effect of P15 on the proliferation of in SHT cells.

  10. Loss of imprinting and loss of heterozygosity on 11p15.5 in head and neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Rainho, C A; Kowalski, L P; Rogatto, S R

    2001-01-01

    on chromosome 11p15.5, a common site of loss of heterozygosity in human cancers. METHODS: We performed an allelic-typing assay using a PCR-RFLP-based method for identification of heterozygous informative cases in head and neck squamous cell carcinomas. Tumoral total RNA was extracted from each...

  11. Homozygous Deletions and Recurrent Amplifications Implicate New Genes Involved in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Wennuan Liu

    2008-08-01

    Full Text Available Prostate cancer cell lines provide ideal in vitro systems for the identification and analysis of prostate tumor suppressors and oncogenes. A detailed characterization of the architecture of prostate cancer cell line genomes would facilitate the study of precise roles of various genes in prostate tumorigenesis in general. To contribute to such a characterization, we used the GeneChip 500K single nucleotide polymorphic (SNP array for analysis of genotypes and relative DNA copy number changes across the genome of 11 cell lines derived from both normal and cancerous prostate tissues. For comparison purposes, we also examined the alterations observed in the cell lines in tumor/normal pairs of clinical samples from 72 patients. Along with genome-wide maps of DNA copy number changes and loss of heterozygosity for these cell lines, we report previously unreported homozygous deletions and recurrent amplifications in prostate cancers in this study. The homozygous deletions affected a number of biologically important genes, including PPP2R2A and BNIP3L identified in this study and CDKN2A/CDKN2B reported previously. Although most amplified genomic regions tended to be large, amplifications at 8q24.21 were of particular interest because the affected regions are relatively small, are found in multiple cell lines, are located near MYC, an oncogene strongly implicated in prostate tumorigenesis, and are known to harbor SNPs that are associated with inherited susceptibility for prostate cancer. The genomic alterations revealed in this study provide an important catalog of positional information relevant to efforts aimed at deciphering the molecular genetic basis of prostate cancer.

  12. Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci.

    Science.gov (United States)

    Kachuri, Linda; Amos, Christopher I; McKay, James D; Johansson, Mattias; Vineis, Paolo; Bueno-de-Mesquita, H Bas; Boutron-Ruault, Marie-Christine; Johansson, Mikael; Quirós, J Ramón; Sieri, Sabina; Travis, Ruth C; Weiderpass, Elisabete; Le Marchand, Loic; Henderson, Brian E; Wilkens, Lynne; Goodman, Gary E; Chen, Chu; Doherty, Jennifer A; Christiani, David C; Wei, Yongyue; Su, Li; Tworoger, Shelley; Zhang, Xuehong; Kraft, Peter; Zaridze, David; Field, John K; Marcus, Michael W; Davies, Michael P A; Hyde, Russell; Caporaso, Neil E; Landi, Maria Teresa; Severi, Gianluca; Giles, Graham G; Liu, Geoffrey; McLaughlin, John R; Li, Yafang; Xiao, Xiangjun; Fehringer, Gord; Zong, Xuchen; Denroche, Robert E; Zuzarte, Philip C; McPherson, John D; Brennan, Paul; Hung, Rayjean J

    2016-01-01

    Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.

  13. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;

    2010-01-01

    chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12...... with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III...

  14. Evaluation of cell binding peptide (p15) with silk fibre enhanced hydroxyappatite bone substitute for posterolateral spinal fusion in sheep

    DEFF Research Database (Denmark)

    Axelsen, M.; Jespersen, Stig; Overgaard, Søren;

    2015-01-01

    Background: Spinal fusion is indicated in the surgical management of various spinal disorders. To ensure stabile fusion, bone graft materials are essential. Traditionally allo- or autograft has been used, but both are associated with limitations. Synthetic bone graft materials that reassemble today...... on the surface of bone forming cells. The binding initiates natural intra- and extracellular signalling pathways, inducing production of growth factors, bone morphogenic proteins and cytokines. P15 peptide has previously shown to improve osteoinductive properties when coated on graft materials. Purpose...... two level uninstrumented PLF at level L2/L3 and L4/L5. Levels were randomised to receive silk fibre enhanced ABM graft with or graft without P15 coating. The sheep were sacrificed after 4.5 months. Levels were harvested and evaluated with Micro-CT 50 scanner and qualitative histology. Fusion rates...

  15. P15INK4B基因甲基化与骨髓增生异常综合征

    Institute of Scientific and Technical Information of China (English)

    叶雪石; 刘霆

    2004-01-01

    骨髓增生异常综合征(MDS)是一种造血干细胞的克隆性疾病,容易进展为急性白血病.P15INK4B基因为人类肿瘤抑制基因,在负向调节造血细胞增生和阻止其恶性转换中起着重要的作用.近来研究显示P15INK4B基因高度甲基化与MDS的发生、发展具重要关系,越是疾病进展期,P15INK4B基因甲基化出现越频繁.5-氮杂胞苷(5-azacytidine)和5-杂氮-2'-脱氧胞嘧啶(decitabine)用于治疗MDS患者已取得一定效果,三氧化二砷的体外试验显示其具有抑制MDS细胞株生长和去甲基化作用.去甲基化治疗有望成为今后治疗MDS的有效方案之一.

  16. Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in primary gastric adenocarcinomas

    Institute of Scientific and Technical Information of China (English)

    Yuan-Yuan Liu; Hai-Ying Chen; Man-Li Zhang; Dan Tian; Shibo Li; Ji-Yun Lee

    2012-01-01

    AIM:To investigate the genomic copy number alterations that may harbor key driver genes in gastric tumorigenesis.METHODS:Using high-resolution array comparative genomic hybridization (CGH),we investigated the genomic alterations of 20 advanced primary gastric adenocarcinomas (seventeen tubular and three mucinous)of Chinese patients from the Jilin province.Ten matching adjacent normal regions from the same patients were also studied.RESULTS:The most frequent imbalances detected in these cancer samples were gains of 3q26.31-q27.2,5p,8q,11p,18p,19q and 20q and losses of 3p,4p,18q and 21q.The use of high-resolution array CGH increased the resolution and sensitivity of the observed genomic changes and identified focal genetic imbalances,which included 54 gains and 16 losses that were smaller than 1 Mb in size.The most interesting focal imbalances were the intergenic loss/homozygous deletion of the fragile histidine triad gene and the amplicons 11q13,18q11.2 and 19q12,as well as the novel amplicons 1p36.22 and 11p15.5.CONCLUSION:These regions,especially the focal amplicons,may harbor key driver genes that will serve as biomarkers for either the diagnosis or the prognosis of gastric cancer,and therefore,a large-scale investigation is recommended.

  17. P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial

    OpenAIRE

    Gomar, Francisco; Orozco, Rafael; Villar, Jose Luis; Arrizabalaga, Federico

    2006-01-01

    Treatment of non-unions and delayed unions often requires osteogenic material. Recently, a biomimetic bone matrix that simulates the cellular environment of hard tissue, identified as P-15, was introduced to the orthopaedic community. A total of 22 patients with mal-union or delayed union fractures was treated from June 2000 to October 2003 with P15- bone graft substitute (P15-BGS) in the site of fracture and mostly with internal fixation. Patients were examined by independent radiographic an...

  18. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15.

    OpenAIRE

    Boehm, T.; Baer, R; Lavenir, I; Forster, A; Waters, J J; Nacheva, E; Rabbitts, T H

    1988-01-01

    A chromosomal translocation t(11;14) (p15;q11) is described in a human acute T-cell leukaemia of immature phenotype (CD3-, CD4-, CD8-). The translocation occurs at a T-cell receptor joining J delta segment, 12 kb upstream of the constant C delta gene and 98 kb upstream of the C alpha gene at chromosome band 14q11. Nucleotide sequencing shows that both J delta and C delta are very conserved between mouse and man. The region of chromosome 11 involved in the translocation is transcriptionally ac...

  19. Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishna, U.; Mehenni, H.; Antonarakis, S.E. [Geneva Medical School (Switzerland)] [and others

    1997-03-01

    Postaxial polydactyly type-A (PAP-A) in humans is an autosomal dominant trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. The extra digit is well formed and articulates with the fifth, or extra, metacarpal/metatarsal, and thus it is usually functional. In order to map the gene responsible for PAP-A, we studied a five-generation Indian family of 37 individuals (15 of whom were affected). A genomewide search with highly informative polymorphic markers on part of the pedigree showed linkage between the PAP-A phenotype and markers on chromosome 7p15-q11.23 (no crossovers were found with D7S526, D7S795, D7S528, D7S521, D7S691, D7S667, D7S478, D7S1830, D7S803, D7S801, or ELN). The highest LOD score was obtained with marker D7S801 (Z{sub max} = 4.21; {theta} = 0). Haplotype analysis enabled the mapping of the PAP-A phenotype in this family between markers D7S2848 and D7S669. Analysis of additional families with PAP-A will narrow down the critical genomic region, facilitate positional cloning of the PAP-A gene, and/or uncover potential genetic heterogeneity. 42 refs., 4 figs., 1 tab.

  20. Identification of novel RA susceptibility loci at chromosomes 10p15, 12q13 and 22q13

    Science.gov (United States)

    Barton, Anne; Thomson, Wendy; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Plant, Darren; Gibbons, Laura J; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Worthington, Jane

    2009-01-01

    The WTCCC study identified 49 single nucleotide polymorphisms (SNPs) putatively associated with RA at p=1×10-4-1×10-5 (Tier 3). Here, we show that 3 of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend p = 4×10-5, p=4×10-4 and p=4×10-4, respectively) in a validation study of 4,106 RA cases and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in Caucasians. PMID:18794857

  1. The first detection and whole genome characterization of the G6P[15] group A rotavirus strain from roe deer.

    Science.gov (United States)

    Jamnikar-Ciglenecki, Urska; Kuhar, Urska; Sturm, Sabina; Kirbis, Andrej; Racki, Nejc; Steyer, Andrej

    2016-08-15

    Although rotaviruses have been detected in a variety of host species, there are only limited records of their occurrence in deer, where their role is unknown. In this study, group A rotavirus was identified in roe deer during a study of enteric viruses in game animals. 102 samples of intestinal content were collected from roe deer (56), wild boars (29), chamois (10), red deer (6) and mouflon (1), but only one sample from roe deer was positive. Following whole genome sequence analysis, the rotavirus strain D38/14 was characterized by next generation sequencing. The genotype constellation, comprising 11 genome segments, was G6-P[15]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Phylogenetic analysis of the VP7 genome segment showed that the D38/14 rotavirus strain is closely related to the various G6 zoonotic rotavirus strains of bovine-like origin frequently detected in humans. In the VP4 segment, this strain showed high variation compared to that in the P[15] strain found in sheep and in a goat. This finding suggests that rotaviruses from deer are similar to those in other DS-1 rotavirus groups and could constitute a source of zoonotically transmitted rotaviruses. The epidemiological status of group A rotaviruses in deer should be further investigated. PMID:27374907

  2. Effects of Polypeptide P-15 on Attachment,Proliferation and Differentiation of Cultured Osteoblast on Bone Mineral Particles%多肽P-15对大鼠成骨细胞附着增殖分化的影响

    Institute of Scientific and Technical Information of China (English)

    陈筑苏; 周磊; 吴王喜

    2010-01-01

    目的 研究多肽P-15对小牛骨表面生长的大鼠成骨细胞附着、增殖、分化的影响.方法 对照组和实验组分别采用单纯无机小牛骨粉 (anorganic bone mineral,ABM)和复合 P-15的无机小牛骨粉接种大鼠成骨细胞进行体外培养.四甲基偶氮唑蓝[3-(4,5-dimehyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide,MTT]比色法检测大鼠成骨细胞在2组骨粉表面附着、增殖的速度,倒置相差显微镜观察成骨细胞在2组骨粉表面及周围的增殖情况,用对硝基苯磷酸二钠盐(p-nitrophenyl phosphate,PNPP)法检测2组成骨细胞碱性磷酸酶(alkaline phosphatase,ALP)活性.结果成骨细胞体外培养24 h,实验组与对照组MTT比色法检测的光密度值分别为1.597±0.035、 1.239±0.063,差异有统计学意义(P<0.01).培养72 h,实验组和对照组PNPP法检测的ALP活性分别为(35.533±1.051)金氏单位/100 mL和(34.645±1.187)金氏单位/100 mL,实验组略高于对照组,但差异无统计学意义(P>0.05).结论多肽P-15加快了大鼠成骨细胞在骨粉表面粘附、增殖的速度,但对大鼠成骨细胞的分化无明显促进作用.

  3. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders

    DEFF Research Database (Denmark)

    Eggermann, Katja; Bliek, Jet; Brioude, Frédéric;

    2016-01-01

    disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014......Molecular genetic testing for the 11p15-associated imprinting disorders Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these......, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from...

  4. A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

    Directory of Open Access Journals (Sweden)

    Ida Surakka

    2011-10-01

    Full Text Available Recent genome-wide association (GWA studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA data from 18 population-based cohorts with European ancestry (maximum N = 32,225. We collected 8 further cohorts (N = 17,102 for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR on total cholesterol (TC with a combined P-value of 4.79×10(-9. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

  5. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    OpenAIRE

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based...

  6. Fusion peptide P15-CSP shows antibiofilm activity and pro-osteogenic activity when deposited as a coating on hydrophilic but not hydrophobic surfaces.

    Science.gov (United States)

    Li, Xian; Contreras-Garcia, Angel; LoVetri, Karen; Yakandawala, Nandadeva; Wertheimer, Michael R; De Crescenzo, Gregory; Hoemann, Caroline D

    2015-12-01

    In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces.

  7. Fusion peptide P15-CSP shows antibiofilm activity and pro-osteogenic activity when deposited as a coating on hydrophilic but not hydrophobic surfaces.

    Science.gov (United States)

    Li, Xian; Contreras-Garcia, Angel; LoVetri, Karen; Yakandawala, Nandadeva; Wertheimer, Michael R; De Crescenzo, Gregory; Hoemann, Caroline D

    2015-12-01

    In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces. PMID:26097095

  8. Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans. A histologic and morphometric study

    OpenAIRE

    Arthur B. Novaes Jr.; Patricia Garani Fernandes; Flávia Adelino Suaid; Marcio Fernando de Moraes Grisi; Sergio Luis Scombatti de Souza; Mario Taba Jr.; Daniela Bazan Palioto; Valdir Antonio Muglia

    2012-01-01

    Aim: The aim of this study was to analyze by histomorphometric parameters the use of acellular dermal matrix (ADM) with or without anorganic bovine bone matrix (ABM) / synthetic cell-binding peptide P-15 in the formation of bone in human alveoli. Materials and methods: Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15) or the control group (ADM only). Histomorphometric measurements and histological a...

  9. The "putative" leucine zipper region of murine leukemia virus transmembrane protein (P15e) is essential for viral infectivity.

    Science.gov (United States)

    Ramsdale, E E; Kingsman, S M; Kingsman, A J

    1996-06-01

    In order to determine the role of the putative leucine zipper region of murine leukemia virus (MLV) transmembrane protein p15E, nine mutations in this region were introduced by site-directed mutagenesis. None of these mutations affected the expression or transport of the envelope protein or incorporation into virions. The mutants were analyzed for their ability to infect NIH3T3 cells and to induce cell fusion in a rat XC cell fusion assay. Mutations removing the charge of the hydrophilic residues reduced infectivity in NIH3T3 cells but had either no effect or a minor effect on envelope-induced XC cell fusion. Six mutations of hydrophobic residues of the putative leucine zipper region were constructed; four completely abolished the ability to infect NIH3T3 cells and these mutant envelopes were also unable to induce cell fusion in the XC cell fusion assay. These data demonstrate the absolute requirement for the putative leucine zipper region for both fusion and infection of MLV. PMID:8659102

  10. Chromosome r(10(p15.3q26.12 in a newborn child: case report

    Directory of Open Access Journals (Sweden)

    Jonasson Jon

    2009-12-01

    Full Text Available Abstract Background Ring chromosome 10 is a rare cytogenetic finding. Of the less than 10 reported cases we have found in the literature, none was characterized using high-resolution microarray analysis. Ring chromosomes are frequently unstable due to sister chromatid exchanges and mitotic failures. When mosaicism is present, the interpretation of genotype-phenotype correlations becomes extremely difficult. Results We report on a newborn girl with growth retardation, microcephaly, congenital heart defects, dysmorphic features and psychomotor retardation. Karyotyping revealed a non-mosaic apparently stable ring chromosome 10 replacing one of the normal homologues in all analyzed metaphases. High-resolution oligonucleotide microarray analysis showed a de novo approximately 12.5 Mb terminal deletion 10q26.12 -> qter and a corresponding 285 kb terminal deletion of 10pter -> p15.3. Conclusion This case demonstrates that an increased nuchal translucency thickness detected by early ultrasonography should preferably lead to not only QF-PCR for the diagnosis of Down syndrome but also karyotyping. In the future, microarray analysis, which needs further evaluation, might become the method of choice. The clinical phenotype of our patient was in agreement with that of patients with a terminal 10q deletion. For the purpose of genotype-phenotype analysis, there seems to be no need for a "ring syndrome" concept.

  11. Non-Syndromic Brachydactyly Type D and Type E Mapped to 7p15 in Healthy Children and Adults from the Jirel Ethnic Group in Eastern Nepal

    Science.gov (United States)

    Williams, Kimberly D.; Blangero, John; Subedi, Janardan; Jha, Bharat; Dyer, Thomas; VandeBerg, John L.; Towne, Bradford; Williams-Blangero, Sarah

    2014-01-01

    Objectives There is phenotypic overlap between Brachydactyly Type D (BDD) and Brachydactyly Type E (BDE) that suggests a possible common underlying etiology. We seek to understand the genetic underpinnings of, and relationship between, these skeletal anomalies. Methods The Jirel ethnic group of eastern Nepal participates in various genetic epidemiologic studies, including those in which hand-wrist radiographs have been taken to examine skeletal development. 2,130 individuals (969 males; 1,161 females) were phenotyped for BDD/BDE. Of these, 1,722 individuals (773 males; 949 females) were genotyped for 371 STR markers spanning the autosomal genome. Variance components-based linkage analysis was used to conduct a genome-wide linkage scan for QTL influencing the BDD/BDE phenotype. Results BDD was present in 3.55%, and BDE was present in 0.39%, of the study sample. Because of the phenotypic overlap between two traits, affecteds of either type were considered as affected by a single combined phenotype (BDD/BDE) having a prevalence of 3.94%. The additive genetic heritability of BDD/BDE was highly significant (h2 ± SE = 0.89 ± 0.13; p = 1.7×10−11). Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516). Conclusions Possible positional candidate genes in the one-lod support interval of this QTL include TWIST and the HOXA1-A13 cluster. This is the first study to report significant linkage results for BDD/BDE using a large extended pedigree, and the first to suggest that mutations in TWIST and/or the HOXA1-A13 cluster may contribute to these specific skeletal anomalies. PMID:24022874

  12. Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery.

    Science.gov (United States)

    Yang, Ching-Chun; Huang, Er-Yi; Li, Hung-Cheng; Su, Pei-Yi; Shih, Chiaho

    2014-01-01

    Hepatitis B virus (HBV) core protein (HBc) can shuttle between nucleus and cytoplasm. Cytoplasm-predominant HBc is clinically associated with severe liver inflammation. Previously, we found that HBc arginine-rich domain (ARD) can associate with a host factor NXF1 (TAP) by coimmunoprecipitation. It is well known that NXF1-p15 heterodimer can serve as a major export receptor of nuclear mRNA as a ribonucleoprotein complex (RNP). In the NXF1-p15 pathway, TREX (transcription/export) complex plays an important role in coupling nuclear pre-mRNA processing with mRNA export in mammalian cells. Here, we tested the hypothesis whether HBc and HBV specific RNA can be exported via the TREX and NXF1-p15 mediated pathway. We demonstrated here that HBc can physically and specifically associate with TREX components, and the NXF1-p15 export receptor by coimmunoprecipitation. Accumulation of HBc protein in the nucleus can be induced by the interference with TREX and NXF1-p15 mediated RNA export machinery. HBV transcripts encodes a non-spliced 3.5 kb pregenomic RNA (pgRNA) which can serve as a template for reverse transcription. Cytoplasmic HBV pgRNA appeared to be reduced by siRNA treatment specific for the NXF1-p15 complex by quantitative RT-qPCR and Northern blot analyses. This result suggests that the pgRNA was also exported via the NXF1-p15 machinery. We entertain the hypothesis that HBc protein can be exported as an RNP cargo via the mRNA export pathway by hijacking the TREX and NXF1-p15 complex. In our current and previous studies, HBc is not required for pgRNA accumulation in the cytoplasm. Furthermore, HBc ARD can mediate nuclear export of a chimeric protein containing HBc ARD in a pgRNA-independent manner. Taken together, it suggests that while both pgRNA and HBc protein exports are dependent on NXF1-p15, they are using the same export machinery in a manner independent of each other.

  13. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  14. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C; Sampson, Joshua N; Hoskins, Jason W; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S; Abnet, Christian C; Adjei, Andrew A; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E; Ambrosone, Christine B; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Arici, Cecilia; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Beane Freeman, Laura E; Berg, Christine D; Berndt, Sonja I; Bertazzi, Pier Alberto; Biritwum, Richard B; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brennan, Paul; Brinton, Louise A; Brotzman, Michelle; Bueno-de-Mesquita, H Bas; Buring, Julie E; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P; Chu, Lisa W; Clavel-Chapelon, Francoise; Colditz, Graham A; Colt, Joanne S; Conti, David; Cook, Michael B; Cortessis, Victoria K; Crawford, E David; Cussenot, Olivier; Davis, Faith G; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P; Di Stefano, Anna Luisa; Diver, W Ryan; Duell, Eric J; Elena, Joanne W; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D; Flanagan, Adrienne M; Fraumeni, Joseph F; Freedman, Neal D; Fridley, Brooke L; Fuchs, Charles S; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M; Gaziano, J Michael; Gerhard, Daniela S; Giffen, Carol A; Giles, Graham G; Gillanders, Elizabeth M; Giovannucci, Edward L; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H; Gross, Myron; Grossman, H Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A; Hallmans, Goran; Hankinson, Susan E; Harris, Curtis C; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B; He, Qincheng; Helman, Lee; Henderson, Brian E; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Hosgood, H Dean; Hsiao, Chin-Fu; Hsing, Ann W; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J; Inskip, Peter D; Ito, Hidemi; Jacobs, Eric J; Jacobs, Kevin B; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M; Klein, Alison P; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kratz, Christian P; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P; Le Marchand, Loic; Lerner, Seth P; Li, Donghui; Liao, Linda M; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A; McKean-Cowdin, Roberta; McNeill, Lorna H; McWilliams, Robert R; Melin, Beatrice S; Meltzer, Paul S; Mensah, James E; Miao, Xiaoping; Michaud, Dominique S; Mondul, Alison M; Moore, Lee E; Muir, Kenneth; Niwa, Shelley; Olson, Sara H; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A; Rodabough, Rebecca J; Rothman, Nathaniel; Ruder, Avima M; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R; Schwartz, Ann G; Schwartz, Kendra L; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart

    2014-12-15

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  15. Cytoplasmic TERT Associates to RNA Granules in Fully Mature Neurons: Role in the Translational Control of the Cell Cycle Inhibitor p15INK4B.

    Directory of Open Access Journals (Sweden)

    Francesca Iannilli

    Full Text Available The main role of Telomerase Reverse Transcriptase (TERT is to protect telomere length from shortening during cell division. However, recent works have revealed the existence of a pool of TERT associated to mitochondria, where it plays a role in survival. We here show that in fully differentiated neurons the largest pool of cytoplasmic TERT associates to TIA1 positive RNA granules, where it binds the messenger RNA of the cyclin kinase inhibitor p15INK4B. Upon stress, p15INK4B and TERT dissociate and p15INK4B undergoes efficient translation, allowing its pro-survival function. These results unveil another mechanism implicated in the survival of fully differentiated neurons.

  16. Interleukins 4 and 13 modulate gene expression and promote proliferation of primary human tenocytes

    Directory of Open Access Journals (Sweden)

    Courneya Jean-Paul

    2010-06-01

    Full Text Available Abstract Background Tendon disorders (tendinopathies pose serious biomedical and socioeconomic problems. Despite diverse treatment approaches, the best treatment strategy remains unclear. Surgery remains the last resort because of the associated morbidity and inconsistent outcomes. We hypothesized that, similar to fibroblasts in various organs, tendon fibroblasts (tenocytes might be responsive to stimulation with interleukins (ILs, particularly IL-4 and IL-13. These two cytokines share sequence homology, receptor chains and functional effects, including stimulation of fibrogenesis. It is unknown whether tenocytes are responsive to stimulation with IL-4 or IL-13. If true, local use of these cytokines might be used to facilitate tendon repair in patients with tendinopathies or used for tendon tissue-engineering approaches to facilitate tenocyte growth on scaffolds in culture. Results Tendon tissues that would normally be discarded were obtained during reconstructive surgery procedures performed for clinical indications. Primary tenocytes were derived from Achilles, posterior tibial, flexor digitorum longus and flexor hallucis longus tendon tissue samples. Reverse transcriptase quantitative PCR (RT-qPCR experiments revealed that mRNAs for the receptor (R chains IL-4Rα, IL-13Rα1 and IL-13Rα2, but not the common γ-chain were present in all tested tendon tissues and in cultured tenocytes. Levels of IL-13R chain mRNAs were significantly higher than those of IL-4R mRNA. The cultures responded, in a dose-dependent fashion, to stimulation with recombinant human IL-4 or IL-13, by increasing proliferation rates 1.5 to 2.0-fold. The mRNA levels of 84 genes related to cell cycle regulation were measured by RT-qPCR after 6 h and 24 h of activation. The expression levels of several genes, notably CDK6 and CDKN2B changed more than twofold. In contrast to their effects on proliferation, stimulation with IL-4 or IL-13 had little if any effect on the levels of

  17. Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11(q11.2;p15.1 translocation

    Directory of Open Access Journals (Sweden)

    Leszl Anna

    2008-10-01

    Full Text Available Abstract Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11(q11.2;p15.1 translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 (Hermansky Pudlak syndrome 5 intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692. Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation.

  18. Clinical and molecular characterization of two patients with overlapping de novo microdeletions in 2p14-p15 and mild mental retardation

    DEFF Research Database (Denmark)

    Wohlleber, Eva; Kirchhoff, Eva Maria; Zink, Alexander M;

    2011-01-01

    Here, we present two patients with overlapping de novo microdeletions in chromosome 2p14-p15, mild mental retardation concerning especially language development, as well as mild dysmorphic features. Patient 1 also presented with generalized seizures, sensorineural hearing loss, and relative micro...

  19. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.

    NARCIS (Netherlands)

    Truong, T.; Hung, R.J.; Amos, C.I.; Wu, X.; Bickeboller, H.; Rosenberger, A.; Sauter, W.; Illig, T.; Wichmann, H.E.; Risch, A.; Dienemann, H.; Kaaks, R.; Yang, P.; Jiang, R.; Wiencke, J.K.; Wrensch, M.; Hansen, H.; Kelsey, K.T.; Matsuo, K.; Tajima, K.; Schwartz, A.G.; Wenzlaff, A.; Seow, A.; Ying, C.; Staratschek-Jox, A.; Nurnberg, P.; Stoelben, E.; Wolf, J.; Lazarus, P.; Muscat, J.E.; Gallagher, C.J.; Zienolddiny, S.; Haugen, A.; Heijden, H.F. van der; Kiemeney, L.A.L.M.; Isla, D.; Mayordomo, J.I.; Rafnar, T.; Stefansson, K.; Zhang, Z.F.; Chang, S.C.; Kim, J.H.; Hong, Y.C.; Duell, E.J.; Andrew, A.S.; Lejbkowicz, F.; Rennert, G.; Muller, H.; Brenner, H.; Marchand, L. le; Benhamou, S.; Bouchardy, C.; Teare, M.D.; Xue, X.; McLaughlin, J.; Liu, G.; McKay, J.D.; Brennan, P.; Spitz, M.R.

    2010-01-01

    BACKGROUND: Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we cond

  20. p15INK4B methylation on prognosis and response to decitabine in patients with MDS%p15INK4B甲基化与骨髓增生异常综合征患者预后及地西他滨疗效的关系

    Institute of Scientific and Technical Information of China (English)

    张耀; 宋陆茜; 吴凌云; 常春康; 李晓

    2013-01-01

    Objective To detect p15INK4B methylation levels and the kinetics of the methylation status before and after decitabine to explore its influences on prognosis and response to decitabine in myelodysplastic syndromes (MDS) patients.Methods We examined 261 MDS patients (143 male and 118 female) with the median age of 52 years (32-78).Of them,172 cases were low-risk group (low-risk 104 cases,intermediate-1 68 cases),89 cases high-risk group (intermediate-2 52 cases,high risk 37 cases).Collections of bone marrow mononuclear cells of MDS patients and extracted the genomic DNA,the methylation status of p15INK4B was detected by methylation-specific PCR (MSP) method.Survival analysis was conducted according to the level of p15INK4B methylation in the cohort of patients.The kinetics of the methylation levels of p15INK4B in 58MDS patients before and after 2 courses of decitabine have been assessed with the method of MSP.Results The methyiation level of p15INK4B in low-risk group patients was significantly lower than that in high-risk group (117.22 vs 157.63,P <0.05).The expected 2-year survival rate of p15INK4B methylation positive patients was lower than that of negative ones (91.8% vs 69.8%,P < 0.05) ; the expected 2-year survival rate of p15INK4B methylation positive patients was shorter than that of negative ones in low-risk group (78.2% vs 92.0%,P <0.05),meanwhile there was no significant difference in terms of expected 2-year survival rate and median expected survival between p15INK4B methylation positive and negative patients in high-risk group [35.6% vs 38.5%,(17.0 ± 9.3) month vs (18.0 ± 5.7) month,P > 0.05].Multivariate analysis showed p15INK4B methylation degree was an independent prognostic factor for overall survival.No statistical difference of overall response (OR) rates were found between p15INK4B methylation positive patients and negative patients before decitabine(65.9% vs 76.5%,P > 0.05),and complete remission (CR) rates between

  1. Infantile spasms in a boy with an abnormal karyotype (46, XY, der(9t(7;9(p15;p22pat

    Directory of Open Access Journals (Sweden)

    Min Zhong

    2014-01-01

    Full Text Available Infantile spasm (IS is an epilepsy syndrome affecting infants and young toddlers and many causes have been reported, including occasional chromosomal abnormalities. We describe a 6-month-oldboy who experienced his first seizure at 5 months of age. The seizures were characterized by brief head nods and forceful flexion of the trunk and limbs. The patient has been developmentally delayed since birth and had deteriorated remarkably in the last month. Interictal electroencephalography showed modified hypsarrhythmia. Magnetic resonance imaging showed delayed myelination and widened brain extracellular space. Chromosomal analysis revealed the karyotype 46, XY, der(9 t(7;9(p15;p22 pat. His father has the asymptomatic reciprocal translocation t(7;9(p15;p22. This chromosomal abnormality is probably the etiology for the ISs and severe developmental anomalies in this patient. Chromosomal analysis may be done in patients with IS with no obvious cause.

  2. Autosomal dominant congenital cataract in a Libyan Jewish family: cosegregation with a reciprocal chromosomal translocation [t(3;5)(p22.3; p15.1)

    OpenAIRE

    Zafer, Emre; Meck, Jeanne; Gerrad, Liora; Pras, Elon; Frydman, Moshe; Reish, Orit; Avni, Isaac; Pras, Eran

    2008-01-01

    Purpose To describe a Jewish family of Libyan ancestry in which autosomal dominant congenital cataract segregates with an apparently balanced reciprocal chromosomal translocation. Methods Detailed family history and clinical data were recorded. Cytogenetic studies were performed on 13 family members. Results Embryonal cataracts cosegregated through three generations with a balanced chromosomal translocation [t(3;5)(p22.3; p15.1)] while the unbalanced translocation product, 46,XY,-5,+der(5)t(3...

  3. The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

    Directory of Open Access Journals (Sweden)

    Chao Agnes Hsiung

    2010-08-01

    Full Text Available Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11. This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11. A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20, allelic risk = 1.54, 95% Confidence Interval (CI 1.41-1.68. Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87, and 2.35 (95% CI: 1.95-2.83, respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

  4. Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans. A histologic and morphometric study

    Directory of Open Access Journals (Sweden)

    Arthur B. Novaes Jr

    2012-06-01

    Full Text Available Aim: The aim of this study was to analyze by histomorphometric parameters the use of acellular dermal matrix (ADM with or without anorganic bovine bone matrix (ABM / synthetic cell-binding peptide P-15 in the formation of bone in human alveoli. Materials and methods: Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15 or the control group (ADM only. Histomorphometric measurements and histological analysis were recorded about 6 months after ridge preservation procedures in ten patients. The amount of newly formed bone, the most recently formed bone, fibrous tissue plus marrow spaces and remaining graft particles were measured and analyzed. Results: At 6 months, the new bone area parameter and the percentage of fibrous tissue plus marrow space areas showed higher values to the control group, and statistically significant differences when compared with the test group (p=0.03. Conclusion: The ADM acted as a membrane. The association of ABM/P-15 with ADM resulted in new bone formation within the alveoli, but the results were not considered relevant when used in this indication.

  5. Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Xun, Wei Wei; Brennan, Paul; Tjonneland, Anne; Vogel, Ulla; Overvad, Kim; Kaaks, Rudolf; Canzian, Federico; Boeing, Heiner; Trichopoulou, Antonia; Oustoglou, Erifili; Giotaki, Zoi; Johansson, Mattias; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Lund, Eiliv; Kumle, Merethe; Rodriguez, Laudina; Agudo, Antonio; Sanchez, Maria-Jose; Arriola, Larraitz; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Hallmans, Goran; Rasmuson, Torgny; Khaw, Kay-Tee; Wareham, Nicholas; Key, Tim; Riboli, Elio; Vineis, Paolo

    2011-01-01

    The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in sma

  6. The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

    OpenAIRE

    Chao Agnes Hsiung; Qing Lan; Yun-Chul Hong; Chien-Jen Chen; H Dean Hosgood; I-Shou Chang; Nilanjan Chatterjee; Paul Brennan; Chen Wu; Wei Zheng; Gee-Chen Chang; Tangchun Wu; Jae Yong Park; Chin-Fu Hsiao; Yeul Hong Kim

    2010-01-01

    Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide as...

  7. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  8. The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse

    Directory of Open Access Journals (Sweden)

    Bayrak Aykut

    2003-05-01

    Full Text Available Abstract Background Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs. CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs. Method In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16. Results Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. However, p16 staining was stronger (++ in the oocytes of all primordial, and 57.4 ± 3.1% of primary follicles compared to the remaining primary and more advanced follicles (+. Interestingly, primary follicles with weaker (+ oocyte staining for p16 had significantly larger mean follicle diameter compared to the primary and primordial follicles with stronger (++ oocyte staining (55.6 ± 2.1 vs. 32.0 ± 1.0 and 26.5 ± 0.7 μm, respectively, p Conclusions These preliminary findings suggest that the initiation of oocyte growth, which seems to lead follicle growth, is associated with diminished p16 expression in the mouse ovary. Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth.

  9. Estudo clínico da aplicação de matriz inorgânica de osso associado a peptídeo sintético de adesão celular (MIO/P-15, PepGen P-15®, em lesões periodontais avançadas de cães Clinical study of effectiveness of an anorganic bone matrix and cell-binding peptide (ABM/P-15, PepGen-P15®: application in advanced periodontal lesions of dogs

    Directory of Open Access Journals (Sweden)

    Daniel G. Ferro

    2009-02-01

    Full Text Available Os mecanismos biológicos desenvolvidos para aumentar a qualidade da regeneração óssea e da reparação tecidual de sítios periodontais específicos continuam a ser um desafio e têm sido complementado pela capacidade de adesão celular do colágeno do tipo I, promovida por um peptídeo sintético de adesão celular (P-15, associado a uma matriz inorgânica de osso (MIO para formar MIO/P-15. O objetivo deste estudo foi avaliar a perda do nível clínico de inserção e a resposta da bolsa periodontal em dentes após 3 e 6 meses da aplicação de enxerto com MIO/P-15. Vinte e um cães do Hospital Veterinário da Universidade de São Paulo foram anestesiados para realização de tratamento periodontal e 132 faces dentais com perda de nível clínico de inserção foram tratadas, sendo que 36,4% (48 faces receberam o peptídeo de adesão celular e 63,6% (84 faces compuseram o grupo controle que recebeu tratamento convencional (retalho muco-gengival e aplainamento radicular. O procedimento foi documentado através de radiografia intra-oral e todas as sondagens de bolsas periodontais foram fotografadas. Depois de 3 e de 6 meses, os animais foram re-anestesiados a fim de se obter novas avaliações, radiografias, fotografias e sondagens periodontais. As 48 faces com perda de nível clínico de inserção que receberam material de enxertia apresentaram taxa de 40% de recuperação do nível clínico de inserção após 6 meses. O grupo controle de faces dentais não apresentou alteração do nível clínico de inserção. A face palatina foi a que apresentou melhor taxa de regeneração (40% e os dentes caninos e molares mostraram as melhores respostas (57,14% e 65%, respectivamente. Não houve sinais de infecção pós-cirúrgica relacionadas à falta de higienização oral dos animais. Pode-se concluir que o MIO/P-15 auxilia na regeneração e re-aderência das estruturas periodontais, incluindo osso alveolar. Sua aplicação mostrou-se fácil e

  10. A rare case of a three way complex variant positive Philadelphia translocation involving chromosome (9;11;22)(q34;p15;q11) in chronic myeloid leukemia: A case report

    Science.gov (United States)

    Asif, Muhammad; Hussain, Abrar; Rasool, Mahmood

    2016-01-01

    The t(9;22)(q34;q11) translocation is present in 90–95% of patients with chronic myeloid leukemia (CML). Variant complex translocations have been observed in 5–8% of CML patients, in which a third chromosome other than (9;22) is involved. Imatinib mesylate is the first line breakpoint cluster region-Abelson gene (BCR/ABL)-targeted oral therapy for CML, and may produce a complete response in 70–80% of CML patients in the chronic phase. In the present study, a bone marrow sample was used for conventional cytogenetic analysis, and the fluorescence in situ hybridization (FISH) test was used for BCR/ABL gene detection. A hematological analysis was also performed to determine the white blood cell (WBC) count, red blood cell count, hemoglobin levels, packed and mean cell volumes, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and platelet values of the patient. The hematological analysis of the patient indicated the increased WBC of 186.5×103 cells/µl, and decreased hemoglobin levels of 11.1 g/dl. The FISH test revealed that 67% cells demonstrated BCR/ABL gene translocation. The patient was treated with 400 mg imatinib mesylate daily, and was monitored at various intervals over a 6-month period. The present study reports the rare case of a patient that demonstrates a three-way Philadelphia chromosome-positive translocation involving 46XY,t(9;11;22)(q34;p15;q11)[10], alongside CML in the chronic phase. The translocation was analyzed using cytogenetic and FISH tests. PMID:27602125

  11. Epigenetic mechanisms in the initiation of hematological malignancies

    Directory of Open Access Journals (Sweden)

    Ali Maleki

    2011-10-01

    Full Text Available Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs. Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS, CDKN2B (alias, P15, a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+ cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors are approved for the treatment of MDS.Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments

  12. Miz1 deficiency in the mammary gland causes a lactation defect by attenuated Stat5 expression and phosphorylation.

    Directory of Open Access Journals (Sweden)

    Adrián Sanz-Moreno

    Full Text Available Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4 or Cdkn1a (p21(Cip1. The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1ΔPOZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR and ErbB4, both critical for Stat5 phosphorylation (pStat5 or pStat5 nuclear translocation, was decreased in Miz1ΔPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype.

  13. 利用14N(d,p)15N核反应对各品系小麦种子中蛋白质含量分析初探%THE ANALYSES OF PROTEIN CONTENTS IN WHEAT SEEDS BY USING 14N(d, p)15N REACTION

    Institute of Scientific and Technical Information of China (English)

    罗小兵; 宣朴; 等

    2000-01-01

    The rates of 14N/12/C in wheat seeds wene measured by using 14N(d, p)15N and 12C(d,p) 13C reactions induced by 13.4MeV deuterons which wene produced by a cylotron. According to the measured 14N/12C rates, the relative protein contents in different wheat sorts were defermined and compared with the results obtained by the Kjeldahl method.

  14. Experimental resolution of deuterium and hydrogen depth profiling with the nuclear reactions D(3He,p)α and p(15N,α,γ)12C

    International Nuclear Information System (INIS)

    In this paper well defined test samples are used to show how the analysis depth and the matrix material influence the depth resolution of nuclear reaction analysis. The reaction D(3He,p)α is used to detect deuterium. By covering 10 nm thin deuterated amorphous carbon (a–C:D) films on silicon with tungsten (ZW = 74) and titanium (ZTi = 22) of various thicknesses between 500 nm and 8 μm the influence of the atomic number and the overlayer thickness on the depth resolution is studied. The most probable depth profiles are calculated from the experimental data with the program NRADC, which implements Bayesian statistics. The resulting apparent layer width of the deuterium containing layer broadens with increasing thickness of the coating and this broadening is more pronounced for coatings with higher Z. These apparent layer widths are a measure for the experimentally achievable depth resolution. Their absolute values are in the same range as the theoretical optimum calculated with RESOLNRA. To investigate the depth resolution of the p(15N,α,γ)12C reaction, a 12 nm thin hydrogenated amorphous carbon (a–C:H) film on silicon and a pure tungsten sample are analysed. The width of the instrument function of this method is deduced from the surface hydrogen peak of the pure tungsten sample. The two methods are compared

  15. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver–Russell and Beckwith–Wiedemann syndrome

    Science.gov (United States)

    Eggermann, Katja; Bliek, Jet; Brioude, Frédéric; Algar, Elizabeth; Buiting, Karin; Russo, Silvia; Tümer, Zeynep; Monk, David; Moore, Gudrun; Antoniadi, Thalia; Macdonald, Fiona; Netchine, Irène; Lombardi, Paolo; Soellner, Lukas; Begemann, Matthias; Prawitt, Dirk; Maher, Eamonn R; Mannens, Marcel; Riccio, Andrea; Weksberg, Rosanna; Lapunzina, Pablo; Grønskov, Karen; Mackay, Deborah JG; Eggermann, Thomas

    2016-01-01

    Molecular genetic testing for the 11p15-associated imprinting disorders Silver–Russell and Beckwith–Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014 and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer-reviewed and published data, as well as observations of the authors in their practice. However, these guidelines can only provide a snapshot of current knowledge at the time of manuscript submission and readers are advised to keep up with the literature. PMID:27165005

  16. Non-destructive testing of proteins in single seeds using the 14N(d,p)15N and 14N(d,∝)12C reactions

    International Nuclear Information System (INIS)

    A non-destructive nuclear technique aimed for the analysis of proteins in single seeds using the 14N(d,p)15N and 14N(d,∝)12C reactions is implemented. This work was performed at the ININ's Tandem Van der Graaff facility, using a 6 MeV deuteron beam and a surface barrier solid state detector with its associated electronics for the pulse height analysis of the charged particles backscattered from the samples. Well defined populations of five varieties of wheat, and four of corn were used as samples in order to optimize the experimental conditions for the analysis, these results were compared with those obtained using an analytical chemical method (Kjeldahl). The linear regression coefficient (''r'') obtained from the results of these two methods was: r = 0.9 in the case of wheat, and r = 0.7 in the case of corn, which we consider adequate figures for using the non-destructive nuclear technique as an aid or support in agricultural seed protein improvement programs. In adequate geometrical conditions the analysis per seed can take a few seconds, and the exposure to the germ can be as low as ≅1 Rad. (author)

  17. Two families with isolated cat cry without the cri-du-chat syndrome phenotype have an inherited 5p15.3 deletion: Delineation of the larynx malformation region

    Energy Technology Data Exchange (ETDEWEB)

    Gersh, M.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Pasztor, L.M. [Children`s Mercy Hospital, Kansas City, MO (United States)] [and others

    1994-09-01

    The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p). Patients present with a cat-like cry at birth that is usually considered diagnostic of this syndrome. Additional features of the syndrome include failure to thrive, microcephaly, hypertelorism, epicanthal folds, hypotonia, and severe mental retardation. We report on two families in which the patients with 5p deletions have only the characteristic cat-like cry with normal to mildly delayed development. One family has three children with varying levels of developmental delay and a deletion of 5p15.3 that was inherited from the father. The second family has a mother and daughter both presenting with a cat-like cry and normal intelligence. A de novo deletion in a patient with isolated cat cry and mild developmental delay was also identified. The precise locations of the deletions in each family were determined by fluorescent in situ hybridization using lambda phage, cosmids, and YAC clones. Cryptic translocations and mosaicism were not detected in the parents transmitting the deletion. All of the deletion breakpoints map distal to the previously defined cri-du-chat critical region. A YAC contig has been constructed for the chromosomal region implicated in the larynx malformation. DNA clones mapping in this region will be useful diagnostic tools for delineating 5p deletions that result in the typical features of cri-du-chat syndrome with deletions that result in the isolated cat-like cry feature which is associated with a better prognosis.

  18. Molecular epidemiology of rotavirus in children and animals and characterization of an unusual G10P[15] strain associated with bovine diarrhea in south India.

    Science.gov (United States)

    Rajendran, Priya; Kang, Gagandeep

    2014-08-11

    Rotaviruses are enteric pathogens causing acute, watery, dehydrating diarrhea in various host species, including birds and mammals. This study collected data on the disease burden and strain prevalence of Group A rotavirus in animals and humans in Vellore and investigated interspecies transmission by comparison of circulating genotypes. Stool samples from children aged less than 5 years, admitted to the hospital between January 2003 and May 2006 for diarrhea and diarrheal samples from animals that were collected from a veterinary clinic and several dairy farms near Vellore between February 2007 and May 2008 were processed and subjected to RNA extraction and reverse-transcription PCR for genotyping of VP7 and VP4. Of 394 children with diarrhea, 158 (40%) were positive for rotavirus and the common G types identified were G1 (47, 29.7%), G2 (43, 27.2%), G9 (22, 13.9%), G10 (2, 1.2%), G12 (1, 0.6%) and mixed infections (27, 17.8%). The common P types were P[4] accounting for 57 (36%) samples, P[8] 57 (36%), P[11] 3 (1.8%) and P[6] 2 (1.2%). Of 627 animals, 35 (1 bullock, 2 goats, 32 cows) were found to be infected with rotavirus (5.5%). The common G types identified in order of frequency were G6 (17, 48.5%), G2 (10, 28%), G10 (4, 11%), G8 (2, 5.7%) and mixed infections (2, 5.7%). The common P types were P[6] accounting for 16 (46%) samples, P[4] 7 (20%), P[1] 3 (8.5%) and P[8] 3 (8.5%). An unusual P type P[15] was seen in one sample in combination with G10. The finding of G2 infections which are rarely identified in animals implies anthroponotic transmission since this genotype is predominantly associated with infection in humans. PMID:25091687

  19. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  20. A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

    NARCIS (Netherlands)

    Surakka, Ida; Isaacs, Aaron; Karssen, Lennart C.; Laurila, Pirkka-Pekka P.; Middelberg, Rita P. S.; Tikkanen, Emmi; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke-Jan; Lagou, Vasiliki; van der Harst, Pim; Mateo Leach, Irene; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nicholas W.; Struchalin, Maksim V.; Sarin, Antti-Pekka; Kangas, Antti J.; Viikari, Jorma S.; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kristin; Soininen, Pasi; Johansson, Asa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theodore; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Florian; Doering, Angela; Rivadeneira, Fernando; Montgomery, Grant W.; Whitfield, John B.; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson B.; Willemsen, Gonneke; de Geus, Eco J. C.; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn M.; Metspalu, Andres; Stumvoll, Michael; Uitterlinden, Andre G.; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.; Taskinen, Marja-Riitta; Ala-Korpela, Mika; Kaprio, Jaakko; Kyvik, Kirsten O.; Boomsma, Dorret I.; Pedersen, Nancy L.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Peter P.; Spector, Tim D.; Witteman, Jacqueline C. M.; Eriksson, Johan G.; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli T.; Wichmann, H. -Erich; Gieger, Christian; Jaervelin, Marjo-Riitta; Martin, Nicholas G.; Hofman, Albert; McCarthy, Mark I.; Peltonen, Leena; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Ripatti, Samuli

    2011-01-01

    Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for v

  1. A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol

    NARCIS (Netherlands)

    I. Surakka (Ida); A.J. Isaacs (Aaron); L.C. Karssen (Lennart); P.-P.P. Laurila; R.P.S. Middelberg (Rita); E. Tikkanen (Emmi); J.S. Ried (Janina); C. Lamina (Claudia); M. Mangino (Massimo); W. Igl (Wilmar); J.J. Hottenga (Jouke Jan); V. Lagou (Vasiliki); P. van der Harst (Pim); I.M. Leach (Irene Mateo); T. Esko (Tõnu); Z. Kutalik (Zoltán); N.W. Wainwright (Nicholas); M.V. Struchalin (Maksim); A.-P. Sarin; A.J. Kangas (Antti); J. Viikari (Jorma); M. Perola (Markus); T. Rantanen (Taina); A.K. Petersen; P. Soininen (Pasi); A. Johansson (Åsa); N. Soranzo (Nicole); A.C. Heath (Andrew); T. Papamarkou (Theodore); I. Prokopenko (Inga); A. Tönjes (Anke); F. Kronenberg (Florian); A. Döring (Angela); F. Rivadeneira Ramirez (Fernando); G.W. Montgomery (Grant); J.B. Whitfield (John); M. Kähönen (Mika); T. Lehtimäki (Terho); N.B. Freimer (Nelson); G.A.H.M. Willemsen (Gonneke); E.J.C. de Geus (Eco); A. Palotie (Aarno); M.S. Sandhu (Manj); D. Waterworth (Dawn); A. Metspalu (Andres); M. Stumvoll (Michael); A.G. Uitterlinden (André); A. Jula (Antti); G. Navis (Gerjan); C. Wijmenga (Cisca); B.H.R. Wolffenbuttel (Bruce); M.-R. Taskinen; M. Ala-Korpela (Mika); J. Kaprio (Jaakko); K.O. Kyvik (Kirsten Ohm); D.I. Boomsma (Dorret); N.L. Pedersen (Nancy); U. Gyllensten (Ulf); J.F. Wilson (James); I. Rudan (Igor); H. Campbell (Harry); P.P. Pramstaller (Peter Paul); T.D. Spector (Timothy); J.C.M. Witteman (Jacqueline); J.G. Eriksson (Johan); V. Salomaa (Veikko); B.A. Oostra (Ben); O. Raitakari (Olli); H.E. Wichmann (Heinz Erich); C. Gieger (Christian); M.R. Järvelin; N.G. Martin (Nicholas); A. Hofman (Albert); M.I. McCarthy (Mark); Y.S. Aulchenko (Yurii); L. Peltonen (Leena Johanna); P. Tikka-Kleemola (Päivi); S. Ripatti (Samuli)

    2011-01-01

    textabstractRecent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ~25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for

  2. 染色体平衡易位46,XY,t(4;7)(q21;p15)致生长激素缺乏症的临床综合分析%Aggregate clinical analysis of growth hormone deficiency caused by balanced chromosomal translocation of 46, XY, t (4; 7) (q21; p15)

    Institute of Scientific and Technical Information of China (English)

    田莉; 李黎; 杜艳; 陈萍; 沈长新; 张建武

    2012-01-01

    目的 探讨平衡易位携带者对子代的影响.方法 患者及家系成员外周血淋巴细胞常规培养制备染色体,进行核型分析.对患者进行复合刺激试验,采用化学发光法检测生长激素(GH)、促卵泡生成素( FSH)和促黄体生成激素(LH)水平,同时检测其他代谢相关生化指标及相关影象检查.结果 患者核型为46,XY,t(4; 7) (q21; p15),患者母亲核型为46,XX,t(4;7) (q21; p15),其他成员核型正常.患者复合刺激试验示GH分泌反应低下,FSH、LH反应 正常,血清胰岛素样生长因子-Ⅰ (IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP -3)、促肾上腺皮质激素(ACTH)、硫酸去氢表雄酮( DHEA -S)、总睾酮(T)低于参考范围的下限.骨龄11岁,垂体MRI排除脑组织异常.结论 患者的异常表型是由于生长激素缺乏所致,常染色体平衡易位可致子代生长激素缺乏症.%Objective: To investigate the influence of Balanced Chromosomal Translocation Carriers to the filial generation. Methods: The Chromosome was extracted from the peripheral blood lymphocyte of the patient and the family members, karyotype analysis were performed. Compound stimulation experiment was performed on the patient, the expression level of GH, FSH, and LF were detected using chemiluminescence, the expression of some other metabolism related biochemical indicators and image analysis were also performed. Results-. The karyotype of the patient and his mother is 46, XY, t (4;7) (q21;p15) and46, XX, t (4; 7) (q21; pl5) respectively, whereas the karyotypes are normal in the other family members. Compound stimulation experiment showed that in the patient, GH secretion respond is lower, whereas the level of FSH, LH are normal. IGF - 1, IGFBP - 3, ACTH, andrusol, DHEA - S and testosterone are lower than the low limit of reference scope. Bone age is eleven. Brain abnomal was excluded by hypophysis MRI. Conclusion: the abnormal phenotype was due to growth hormone deficiency. We

  3. Role of heme oxygenase-1 in demethylating effects on SKM-1 cells induced by decitabine.

    Science.gov (United States)

    Gao, R; Ma, D; Wang, P; Sun, J; Wang, J S; Fang, Q

    2015-12-22

    We evaluated the influence of heme oxygenase-1 (HO-1) gene inhibition in myelodysplastic syndrome (MDS) cell line SKM-1 on enhancement of the demethylating effects of decitabine on p15, and explored the possible mechanism. DNMT1 gene expression in SKM-1 cells was silenced by being transfected by a constructed siRNA with liposomes. The proliferation inhibition rates after drug treatment were detected by cell counting kit-8 assay. The apoptotic rates were detected by Annexin V/PI assay with flow cytometry. The expressions of p16, p15, TP73, CDH1, ESR1, and PDLIM4 mRNAs were detected by real-time PCR, and those of HO-1, DNMT1, DNMT3A, DNMT3B, HDAC, and p15 proteins were measured by western blot. The degree of methylation of the p15 gene was analyzed by using methylation-specific PCR (MSP). CCK-8 assay showed that after HO-1 gene expression was inhibited; the proliferation rate of SKM-1 cells treated by decitabine (70.91 ± 0.05%) was significantly higher than that of the control group (53.67 ± 0.05%). Flow cytometry showed that the apoptotic rate of SKM- 1 cells treated by decitabine in combination with HO-1 expression inhibition (44.25 ± 0.05%) exceeded that of the cells treated by this drug alone (37.70 ± 0.05%). MSP showed that inhibiting HO-1 expression significantly increased the degree of methylation of the p15 gene. As suggested by western blot, the degree of methylation of the p15 protein was changed after decitabine treatment when the expression of the HO-1 protein was changed, being associated with the affected DNMT1 expression. Inhibited HO-1 expression attenuated the hypermethylation of CDKN2B by suppressing DNMT1, which was conducive to treatment by cooperating with decitabine. In conclusion, the findings of this study provide valuable experimental evidence for targeted MDS therapy, and a theoretical basis for further studies.

  4. Associations of High-Grade Glioma With Glioma Risk Alleles and Histories of Allergy and Smoking

    OpenAIRE

    Lachance, Daniel H.; Yang, Ping; Johnson, Derek R.; Decker, Paul A.; Kollmeyer, Thomas M.; McCoy, Lucie S.; Rice, Terri; Xiao, Yuanyuan; Ali-Osman, Francis; Wang, Frances; Stoddard, Shawn M.; Sprau, Debra J.; Kosel, Matthew L.; Wiencke, John K.; Wiemels, Joseph L.

    2011-01-01

    Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997–2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). Th...

  5. A childhood acute lymphoblastic leukemia (ALL case with t(3;17(q23;p13,t(5;12(q31;p13,inv(11(p15q12

    Directory of Open Access Journals (Sweden)

    Ayse Cirakoglu

    2008-09-01

    Full Text Available It is known that clonal chromosomal changes in childhood ALL are nonrandom and important markers for diagnosis, prognosis and relaps. In this report we present 4 year-old boy with ALL-L1 who has complex chromosomal rearrangements. Chromosome analysis was performed on bone marrow aspiration sample in relaps after one year from diagnosis and induction chemotherapy. The karyotype was; 46,XY,t(3;17(q23;p13,t(5;12(q31;p13,inv(11(p15q12 [11]/46,XY[8

  6. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

    OpenAIRE

    Petersen, Gloria M.; Amundadottir, Laufey; Fuchs, Charles S; Kraft, Peter; Stolzenberg-Solomon, Rachael Z; Jacobs, Kevin B.; Arslan, Alan A.; Bueno-de-Mesquita, H Bas; Gallinger, Steven; Gross, Myron; Helzlsouer, Kathy; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P; LaCroix, Andrea

    2010-01-01

    We conducted a genome-wide association study (GWAS) of pancreatic cancer in 3,851 cases and 3,934 controls drawn from twelve prospective cohort studies and eight case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P=3.27×10−11; per allele odds ra...

  7. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

    Science.gov (United States)

    Petersen, Gloria M.; Amundadottir, Laufey; Fuchs, Charles S.; Kraft, Peter; Stolzenberg-Solomon, Rachael Z.; Jacobs, Kevin B.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gallinger, Steven; Gross, Myron; Helzlsouer, Kathy; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Li, Donghui; Mandelson, Margaret T.; Olson, Sara H.; Risch, Harvey A.; Zheng, Wei; Albanes, Demetrius; Bamlet, William R.; Berg, Christine D.; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Bracci, Paige M.; Canzian, Federico; Clipp, Sandra; Cotterchio, Michelle; de Andrade, Mariza; Duell, Eric J.; Gaziano, J. Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hassan, Manal; Howard, Barbara; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Kaaks, Rudolf; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; Lynch, Shannon M.; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Parikh, Hemang; Patel, Alpa V.; Peeters, Petra H.M.; Rajkovic, Aleksandar; Riboli, Elio; Rodriguez, Laudina; Seminara, Daniela; Shu, Xiao-Ou; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Van Den Eeden, Stephen K.; Virtamo, Jarmo; Wactawski-Wende, Jean; Wang, Zhaoming; Wolpin, Brian M.; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Fraumeni, Joseph F.; Hoover, Robert N.; Hartge, Patricia; Chanock, Stephen J.

    2010-01-01

    We conducted a genome-wide association study (GWAS) of pancreatic cancer in 3,851 cases and 3,934 controls drawn from twelve prospective cohort studies and eight case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P=3.27×10−11; per allele odds ratio, OR 1.26, 95% CI=1.18-1.35) and rs9564966 (P=5.86×10−8; per allele OR 1.21, 95% CI=1.13-1.30) map to a non-genic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2; the strongest signal was rs3790844 (P=2.45×10−10; per allele OR 0.77, 95% CI=0.71-0.84). A single SNP, rs401681 (P=3.66×10−7; per allele OR 1.19, 95% CI=1.11-1.27) maps to the CLPTM1L-TERT locus on 5p15.33, associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies. PMID:20101243

  8. Multiplex FISH telomere integrity assay identifies an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three mentally retarded individuals.

    Science.gov (United States)

    Granzow, M; Popp, S; Keller, M; Holtgreve-Grez, H; Brough, M; Schoell, B; Rauterberg-Ruland, I; Hager, H D; Tariverdian, G; Jauch, A

    2000-07-01

    Cryptic rearrangements involving the terminal regions of chromosomes are suspected to be the cause of idiopathic mental retardation in a significant number of cases. This finding highlights the necessity of a primary screening test for such chromosome aberrations. Here we present a multiplex fluorescence in situ hybridization telomere integrity assay which allows the detection of submicroscopic aberrations in the telomeric regions of all chromosomes. This novel approach identified an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three cases of unexplained mental retardation and dysmorphic features. The symptoms of the patients represent neither the classical dup(3q)- nor cri du chat syndrome, although all affected individuals demonstrate several features of both syndromes. The identification of two balanced translocation carriers emphasizes the significance of the telomere integrity assay for genetic counseling and prenatal diagnosis. PMID:10982035

  9. Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

    DEFF Research Database (Denmark)

    Nagasawa, T; Zhang, Q; Raghunath, P N;

    2006-01-01

    To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-express...

  10. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  11. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  12. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Directory of Open Access Journals (Sweden)

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  13. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    International Nuclear Information System (INIS)

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  14. Immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

  15. Gene expression

    International Nuclear Information System (INIS)

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn2+ or Cd2+. We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  16. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

    Energy Technology Data Exchange (ETDEWEB)

    Owerbach, D.; Gabbay, K.H. (Baylor College of Medicine, Houston, TX (United States))

    1994-05-01

    Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.

  17. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  18. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela; Goedegebuur, Frits; Van Solingen, Pieter; Ward, Michael

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  19. Gene therapy.

    OpenAIRE

    Mota Biosca, Anna

    1992-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases.

  20. New common variants affecting susceptibility to basal cell carcinoma

    OpenAIRE

    Stacey, Simon N.; Sulem, Patrick; Masson, Gisli; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Jakobsdottir, Margret; Sigurdsson, Asgeir; Daniel F Gudbjartsson; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Scherer, Dominique; Hemminki, Kari; Rudnai, Peter

    2009-01-01

    In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC)1, we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10−9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10−9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10−10...

  1. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  2. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  3. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  4. [Language gene].

    Science.gov (United States)

    Takahashi, Hiroshi

    2006-11-01

    The human capacity for acquiring speech and language must derive, at least in part, from the genome. Recent advance in the field of molecular genetics finally discovered 'Language Gene'. Disruption of FOXP2 gene, the firstly identified 'language gene' causes severe speech and language disorder. To elucidate the anatomical basis of language processing in the brain, we examined the expression pattern of FOXP2/Foxp2 genes in the monkey and rat brains through development. We found the preferential expression of FOXP2/Foxp2 in the striosomal compartment of the developing striatum. Thus, we suggest the striatum, particularly striosomal system may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/ procedural model of language proposed by Ullman (1997, 2001), which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex, and the declarative memory-dependent mental lexicon is rooted in the temporal lobe. PMID:17432197

  5. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment.

  6. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment. PMID:26872600

  7. Genes and Psoriasis

    Science.gov (United States)

    ... Diet Tips" to find out more! Email * Zipcode Genes and Psoriasis Genes hold the key to understanding ... is responsible for causing psoriatic disease. How do genes work? Genes control everything from height to eye ...

  8. Genes and Hearing Loss

    Science.gov (United States)

    ... Meeting Calendar Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  9. Gene gymnastics

    Science.gov (United States)

    Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

    2013-01-01

    Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

  10. The utility of quantitative methylation assays at imprinted genes for the diagnosis of fetal and placental disorders.

    Science.gov (United States)

    Bourque, D K; Peñaherrera, M S; Yuen, R K C; Van Allen, M I; McFadden, D E; Robinson, W P

    2011-02-01

    An imbalance of imprinted gene expression within 11p15.5 is observed in Beckwith-Wiedemann syndrome (BWS), as well as in a variety of placental abnormalities including complete hydatidiform mole (CHM), placental mesenchymal dysplasia (PMD) and triploidy. To facilitate the diagnosis of epigenetic errors and chromosomal imbalance of 11p15.5, we validated a pyrosequencing assay to measure methylation at KvDMR1 using blood samples from 13 BWS cases, 8 of which showed reduced methylation as compared to control blood. An imbalance between maternal and paternal genomes as is found in triploidy, CHM or PMD was also associated with altered KvDMR1 methylation. A reciprocal pattern of methylation was obtained in the triploid cases by assaying the proximal 11p15.5 ICR associated with H19. To distinguish chromosome 11 specific alterations from whole genome imbalance, other imprinted differentially methylated regions (DMRs) can be utilized. Thus, pyrosequencing assays for DMRs associated with SGCE, SNRPN, and MEST were also compared for their utility in diagnosing parental imbalance in placental samples. While each of these assays could successfully distinguish parental origin of triploidy, SGCE showed the clearest separation between groups. The combined use of a chromosome 11p15.5 assay (e.g. KvDMR1 or H19-ICR) and non-chromosome 11 assay (e.g. SGCE) provides a potentially valuable diagnostic tool in the rapid screening of methylation errors in placental disorders. These results also show the maintenance of imprinting status at these loci in the human placenta, even in the presence of abnormal pathology.

  11. Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11

    Directory of Open Access Journals (Sweden)

    Bader Scott

    2005-07-01

    Full Text Available Abstract Background Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11. Results In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene. Conclusion Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.

  12. Association of MC3R gene polymorphisms with body weight in the red fox and comparative gene organization in four canids.

    Science.gov (United States)

    Skorczyk, A; Flisikowski, K; Szydlowski, M; Cieslak, J; Fries, R; Switonski, M

    2011-02-01

    There are five genes encoding melanocortin receptors. Among canids, the genes have mainly been studied in the dog (MC1R, MC2R and MC4R). The MC4R gene has also been analysed in the red fox. In this report, we present a study of chromosome localization, comparative sequence analysis and polymorphism of the MC3R gene in the dog, red fox, arctic fox and Chinese raccoon dog. The gene was localized by FISH to the following chromosome: 24q24-25 in the dog, 14p16 in the red fox, 18q13 in the arctic fox and NPP4p15 in the Chinese raccoon dog. A high identity level of the MC3R gene sequences was observed among the species, ranging from 96.0% (red fox--Chinese raccoon dog) to 99.5% (red fox--arctic fox). Altogether, eight polymorphic sites were found in the red fox, six in the Chinese raccoon dog and two in the dog, while the arctic fox appeared to be monomorphic. In addition, association of several polymorphisms with body weight was analysed in red foxes (the number of genotyped animals ranged from 319 to 379). Two polymorphisms in the red fox, i.e. a silent substitution c.957A>C and c.*185C>T in the 3'-flanking sequence, showed a significant association (P < 0.01) with body weight.

  13. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  14. Organization of immunoglobulin genes.

    Science.gov (United States)

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  15. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k+) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k+ gene expression where the H S V-1 t k+ gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([18 F]F H P G; [18 F]-A C V), and pyrimidine- ([123/131 I]I V R F U; [124/131I]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [123/131I]I V R F U imaging with the H S V-1 t k+ reporter gene will be presented

  16. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  17. Identifying Gene Interaction Enrichment for Gene Expression Data

    OpenAIRE

    Jigang Zhang; Jian Li; Hong-Wen Deng

    2009-01-01

    Gene set analysis allows the inclusion of knowledge from established gene sets, such as gene pathways, and potentially improves the power of detecting differentially expressed genes. However, conventional methods of gene set analysis focus on gene marginal effects in a gene set, and ignore gene interactions which may contribute to complex human diseases. In this study, we propose a method of gene interaction enrichment analysis, which incorporates knowledge of predefined gene sets (e.g. gene ...

  18. Autism and Genes

    Science.gov (United States)

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  19. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.;

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes we...

  20. Principles of gene therapy

    Directory of Open Access Journals (Sweden)

    Mammen Biju

    2007-01-01

    Full Text Available Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics and future percepts and the technical and ethical issues of using gene therapy.

  1. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression

    Directory of Open Access Journals (Sweden)

    Mansukhani Mahesh

    2006-05-01

    Full Text Available Abstract Background Cervical Cancer (CC exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo. These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers. Results To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression. Conclusion Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i play a role in CC development, (ii further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii form epigenetic signatures to identify precancerous lesions at risk to progression.

  2. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Science.gov (United States)

    Zhang, Jie Ting; Weng, Zhi Hui; Tsang, Kam Sze; Tsang, Lai Ling; Chan, Hsiao Chang; Jiang, Xiao Hua

    2016-01-01

    The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  3. Known glioma risk loci are associated with glioma with a family history of brain tumours

    DEFF Research Database (Denmark)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika;

    2013-01-01

    family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies...... and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain...... tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically...

  4. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jie Ting Zhang

    Full Text Available The biologic studies of human neural crest stem cells (hNCSCs are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs. For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  5. Gene doping in sports.

    Science.gov (United States)

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement.

  6. Gene therapy in periodontics

    OpenAIRE

    Anirban Chatterjee; Nidhi Singh; Mini Saluja

    2013-01-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person′s genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ′the use of genes as medicine′. It...

  7. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  8. CHROMATIN LOOPS, GENE POSITIONING AND GENE EXPRESSION

    Directory of Open Access Journals (Sweden)

    Sjoerd eHolwerda

    2012-10-01

    Full Text Available Technological developments and intense research over the last years have led to a better understanding of the three-dimensional structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the α- and β-globin gene loci, the antigen receptor loci, the imprinted H19-Igf2 locus and the Hox gene clusters. Collectively, these studies show that regulatory DNA sequences physically contact genes to control their transcription. Proteins set up the three-dimensional configuration of the genome and we will discuss the roles of the key structural organizers CTCF and cohesin, the nuclear lamina and the transcription machinery. Finally, genes adopt non-random positions in the nuclear interior. We will review studies on gene positioning and propose that cell-specific genome conformations can juxtapose a regulatory sequence on one chromosome to a responsive gene on another chromosome to cause altered gene expression in subpopulations of cells.

  9. Immunogenetic Study in Chinese Population with Ankylosing Spondylitis: Are There Specific Genes Recently Disclosed?

    Directory of Open Access Journals (Sweden)

    Jiayu Zhai

    2013-01-01

    Full Text Available Purpose. Ankylosing spondylitis (AS is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population. Recent Findings. In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC, ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions. Summary. This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.

  10. Cochlear Gene Therapy

    OpenAIRE

    Lustig, Lawrence R.; Akil, Omar

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  11. Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer.

    Directory of Open Access Journals (Sweden)

    Martha L Slattery

    Full Text Available BACKGROUND: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. METHODS: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls and rectal (n = 754 cases, 959 controls cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH, SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208. Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300. Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR and rectal cancer (SepX1 increased HRR. CONCLUSIONS: Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is

  12. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  13. Discovering genes underlying QTL

    International Nuclear Information System (INIS)

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  14. Reading and Generalist Genes

    Science.gov (United States)

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  15. A Pilot Study of Gene/Gene and Gene/Environment Interactions in Alzheimer Disease

    OpenAIRE

    Ghebranious, Nader; Mukesh, Bickol; Giampietro, Philip F.; Glurich, Ingrid; Mickel, Susan F.; Waring, Stephen C.; Catherine A McCarty

    2011-01-01

    Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD.

  16. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  17. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko

    2006-01-01

    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  18. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  19. P15.16EVOLUTION OF THE FUNCTIONAL INDEPENDENCE IN GLIOBLASTOMA PATIENTS

    Science.gov (United States)

    Sacko, A.; Hou, M.; Temgoua, M.; Ursu-Billot, R.; Marantidou, A.; Doridam, J.; Coman, I.; Belin, C.; Levy-Piedbois, C.; Carpentier, A.F.

    2014-01-01

    INTRODUCTION: Functional independence in glioblastoma (GBM) patients is a key factor to maintain quality of life. Progression free survival (PFS) and overall survival (OS) have been largely described in the literature. However, the evolution over time of the performance status remains poorly known. OBJECTIVE: To study the time to deterioration of the Karnosky Perfomance Status (KPS) below 70% in an homogeneous population of GBM patients. METHODS: We analyzed all patients treated in our institution between 2008 and 2012. Patients were included if they met the following criteria: age >18 years, histologically confirmed GBM, supratentorial location, post-surgical KPS ≥70%, initial treatment with concomitant radiotherapy (RT) and Temozolomide (no Bevacizumab). Age, tumor location, surgical procedure, steroid dose at RT onset, KPS at 1 month after RT, then every 2 months until death, were collected in all patients. RESULTS: Within the 63 patients studied, median age was 61 years and 75 % underwent surgical resection at time of diagnosis. Forty-eight patients received one or several lines of chemotherapy at recurrence, and 34 patients (54%) were treated with Bevacizumab at one point during their evolution. The median PFS was 8.9 months and the median OS was 17.4 months. Interestingly, the median survival with KPS ≥70 (OS-70%) was 12 months, thus exceeding the median PFS by more than 3 months. OS-70% exceeded PFS by 6 months in 27% of the patients. Deterioration of KPS <70% occurred before progression in only 39% of the patients. Only surgical resection and low dose steroids (<30 mg equivalent prednisone) at RT onset, but not age ( 60 years), initial KPS, tumor location (frontal vs others), or seizures, were statistically associated with increased OS-70% (14,8 vs 4,5 months, p = 0.017; 16,2 vs 7,2 months, p = 0.001, respectively). DISCUSSION: In our series, the first recurrence after the initial treatment with RT and Temozolomide was not associated with loss of functional independence, which usually occurred later during evolution. Surgical resection and low dose steroids, but not age or KPS, appeared as prognosis factors for OS-70%. The impact of Bevacizumab on KPS beyond first progression is currently under study. CONCLUSION: Median survival with KPS ≥70 (OS-70%) and PFS are poorly correlated, OS-70% exceeded PFS by 3 months in half of the patients and by 6 months in a quarter of the patients. Surgical resection and low steroid requirements before RT appear associated with increased OS-70%.

  20. P15.16EVOLUTION OF THE FUNCTIONAL INDEPENDENCE IN GLIOBLASTOMA PATIENTS

    OpenAIRE

    Sacko, A; Hou, M.; Temgoua, M.; Ursu-Billot, R.; Marantidou, A.; Doridam, J.; Coman, I.; Belin, C; Levy-Piedbois, C.; Carpentier, A F

    2014-01-01

    INTRODUCTION: Functional independence in glioblastoma (GBM) patients is a key factor to maintain quality of life. Progression free survival (PFS) and overall survival (OS) have been largely described in the literature. However, the evolution over time of the performance status remains poorly known. OBJECTIVE: To study the time to deterioration of the Karnosky Perfomance Status (KPS) below 70% in an homogeneous population of GBM patients. METHODS: We analyzed all patients treated in our instit...

  1. Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression

    Directory of Open Access Journals (Sweden)

    Farruk M. Lutful Kabir

    2015-12-01

    Full Text Available Breast cancer represents the second most frequent neoplasm in humans and sexually intact female dogs after lung and skin cancers, respectively. Many similar features in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression and response to conventional therapies have supported development of this comparative model as an alternative to mice. The highly conserved similarities between canine and human genomes are also key to this comparative analysis, especially when compared to the murine genome. Studies with canine mammary tumor (CMT models have shown a strong genetic correlation with their human counterparts, particularly in terms of altered expression profiles of cell cycle regulatory genes, tumor suppressor and oncogenes and also a large group of non-coding RNAs or microRNAs (miRNAs. Because CMTs are considered predictive intermediate models for human breast cancer, similarities in genetic alterations and cancer predisposition between humans and dogs have raised further interest. Many cancer-associated genetic defects critical to mammary tumor development and oncogenic determinants of metastasis have been reported and appear to be similar in both species. Comparative analysis of deregulated gene sets or cancer signaling pathways has shown that a significant proportion of orthologous genes are comparably up- or down-regulated in both human and dog breast tumors. Particularly, a group of cell cycle regulators called cyclin-dependent kinase inhibitors (CKIs acting as potent tumor suppressors are frequently defective in CMTs. Interestingly, comparative analysis of coding sequences has also shown that these genes are highly conserved in mammals in terms of their evolutionary divergence from a common ancestor. Moreover, co-deletion and/or homozygous loss of the INK4A/ARF/INK4B (CDKN2A/B locus, encoding three members of the CKI tumor suppressor gene families (p16/INK4A, p14ARF and p15

  2. Evaluating gene × gene and gene × smoking interaction in rheumatoid arthritis using candidate genes in GAW15

    OpenAIRE

    Mei Ling; Li Xiaohui; Yang Kai; Cui Jinrui; Fang Belle; Guo Xiuqing; Rotter Jerome I

    2007-01-01

    Abstract We examined the potential gene × gene interactions and gene × smoking interactions in rheumatoid arthritis (RA) using the candidate gene data sets provided by Genetic Analysis Workshop 15 Problem 2. The multifactor dimensionality reduction (MDR) method was used to test gene × gene interactions among candidate genes. The case-only sample was used to test gene × smoking interactions. The best predictive model was the single-locus model with single-nucleotide polymorphism (SNP) rs247660...

  3. Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: potential role of C-peptide.

    Science.gov (United States)

    Chen, Guanjie; Adeyemo, Adebowale; Zhou, Jie; Chen, Yuanxiu; Huang, Hanxia; Doumatey, Ayo; Lashley, Kerrie; Agyenim-Boateng, Kofi; Eghan, Benjamin A; Acheampong, Joseph; Fasanmade, Olufemi; Johnson, Thomas; Okafor, Godfrey; Oli, Johnnie; Amoah, Albert; Rotimi, Charles

    2007-12-01

    C-peptide is a substance that the pancreas releases into the circulation in equimolar amounts to insulin and has demonstrated important physiological effects which relate to the vascular field, in particular the microcirculation. For this analysis, we included 321 full and 36 half sibling pairs affected with type 2 diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a total of 691 persons. Variance components based on multipoint linkage approach as implemented in SOLAR were performed for log C-peptide. Significant linkage evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p-value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score 2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p-value=0.0094). Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23. In conclusion, we identified four major genetic loci (10q23, 4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with T2D.

  4. A splicing mutation of the HMGA2 gene is associated with Silver-Russell syndrome phenotype.

    Science.gov (United States)

    De Crescenzo, Agostina; Citro, Valentina; Freschi, Andrea; Sparago, Angela; Palumbo, Orazio; Cubellis, Maria Vittoria; Carella, Massimo; Castelluccio, Pia; Cavaliere, Maria Luigia; Cerrato, Flavia; Riccio, Andrea

    2015-06-01

    Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and post-natal growth retardation, dysmorphic facial features and body asymmetry. About 50% of the patients carry (epi)genetic alterations involving chromosomes 7 or 11.The high proportion of patients with unidentified molecular etiology suggests the involvement of other genes. Interestingly, SRS patients share clinical features with the 12q14 microdeletion syndrome, characterized by several deletions with a 2.6 Mb region of overlap. Among the genes present in this interval, high mobility AT-hook 2 (HMGA2) appears to be the most likely cause of the growth deficiency, due to its described growth control function. To define the role of HMGA2 in SRS, we looked for 12q14 chromosome imbalances and HMGA2 mutations in a cohort of 45 patients with growth retardation and SRS-like phenotype but no 11p15 (epi)mutations or maternal uniparental disomy of chromosome 7 (matUPD7). We identified a novel 7 bp intronic deletion in HMGA2 present in heterozygosity in the proband and her mother both displaying the typical features of SRS. We demonstrated that the deletion affected normal splicing, indicating that it is a likely cause of HMGA2 deficiency. This study provides the first evidence that a loss-of-function mutation of HMGA2 can be associated with a familial form of SRS. We suggest that HMGA2 mutations leading to haploinsufficiency should be investigated in the SRS patients negative for the typical 11p15 (epi)mutations and matUPD7. PMID:25809938

  5. Delivery Systems in Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    Liu Hu; Anas El-Aneed; Cui Guohui

    2005-01-01

    1 Gene therapy Gene therapy includes the treatment of both genetically based and infectious diseases by introducing genetic materials which have therapeutic effects[1~3]. In its simplest terms, a wild type gene (which is non-functional in the cell leading to disease development) is introduced into the somatic cell lacking this gene to restore the normal gene function in this cell. Many gene therapy strategies, however, utilize genes to destroy specific cells.

  6. Gene Conversion and Evolution of Gene Families: An Overview

    OpenAIRE

    Tomoko Ohta

    2010-01-01

    The importance of gene conversion for the evolution of gene families is reviewed. Four problems concerning gene conversion, i.e., concerted evolution, generation of useful variation, deleterious effects, and relation to neofunctionalization, are discussed by surveying reported examples of evolving gene families. Emphasis is given toward understanding interactive effects of gene conversion and natural selection.

  7. Gene promoters dictate histone occupancy within genes.

    Science.gov (United States)

    Perales, Roberto; Erickson, Benjamin; Zhang, Lian; Kim, Hyunmin; Valiquett, Elan; Bentley, David

    2013-10-01

    Spt6 is a transcriptional elongation factor and histone chaperone that reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6 preferentially maintains nucleosomes within the first 500 bases of genes and helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6-depleted cells, H3 loss at 5' ends correlates with reduced pol II density suggesting enhanced transcription elongation. Consistent with its 'Suppressor of Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2 nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with similar pol II densities. More eviction occurred on genes with 'closed' promoters, associated with 'noisy' transcription. Moreover, swapping of 'open' and 'closed' promoters showed that they can specify distinct downstream patterns of histone eviction/deposition. These observations suggest a novel function for promoters in dictating histone dynamics within genes possibly through effects on transcriptional bursting or elongation rate.

  8. DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis

    Science.gov (United States)

    Jiang, Danjie; Li, Yirun; Hong, Qingxiao; Shen, Yusheng; Xu, Chunjing; Xu, Yan; Zhu, Huangkai; Dai, Dongjun; Ouyang, Guifang; Duan, Shiwei

    2016-01-01

    Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated. A total of 4,325 leukemia patients and 2,010 controls from 94 studies on 53 genes were included in this meta-analysis, and 47 genes were found to be aberrantly methylated in leukemia patients. A further subgroup meta-analysis by leukemia subtype demonstrated that hypermethylation of 5 genes, namely cyclin-dependent kinase (CDKN)2A, DNA-binding protein inhibitor-4, CDKN2B, glioma pathogenesis-related protein 1 and p73, contributed to the risk of various subtypes of leukemia. In addition, a strong association between CDKN2A and leukemia was identified in Chinese (Pleukemia in Chinese patients.

  9. Lamins and their genes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The nuclear lamina is an important nuclear structure. The studies on its peptides lamins and genes have made substantial progress in recent years. In this paper, the new achievements in studies of new lamin members and their functions, lamin genes and their origin and differentiation, are reviewed and discussed. Some research areas that deserve to be investigated further are put forward.

  10. Your Genes, Your Choices

    Science.gov (United States)

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  11. Delivery of cationic polymer-siRNA nanoparticles for gene therapies in neural regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Yanran [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Liu, Zhonglin, E-mail: zhonglinliu@126.com [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Shuai, Xintao; Wang, Weiwei [School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, People' s Republic of China (China); Liu, Jun [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Bi, Wei [Department of Neurology, The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Road, Guangzhou 510630, People' s Republic of China (China); Wang, Chuanming; Jing, Xiuna; Liu, Yunyun [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Tao, Enxiang, E-mail: taoenxiang@yahoo.com.cn [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Nogo receptor can inhibit growth of injured axons, thus affecting neural regeneration. Black-Right-Pointing-Pointer The delivery of siRNA is crucial to inhibit NgR expression in NSCs. Black-Right-Pointing-Pointer Non-viral vector PEG-PEI condensed siRNA targeting NgR into nanoscale particles. Black-Right-Pointing-Pointer PEG-PEI/siRNA at N/P = 15 displayed high transfection efficiency and low cytotoxicity. Black-Right-Pointing-Pointer PEG-PEI has great potential in carrying siRNA to diminish the gene expression in NSCs. -- Abstract: The therapeutic applications of neural stem cells (NSCs) have potential to promote recovery in many obstinate diseases in central nervous system. Regulation of certain gene expressions using siRNA may have significant influence on the fate of NSC. To achieve the optimum gene silencing effect of siRNA, non-viral vector polyethylene glycol-polyethyleneimine (PEG-PEI) was investigated in the delivery of siRNA to NSCs. The characteristics of PEG-PEI/siRNA polyplexes were detected by scanning electron microscopy (SEM). The effects of nanoparticles on cell viability were measured via CCK-8 assay. In addition, the transfection efficiency was evaluated by fluorescence microscope and flow cytometry, and real-time PCR and Western Blot were employed to detect the gene inhibition effect of siRNA delivered by PEG-PEI. The SEM micrographs showed that PEG-PEI could condense siRNA to form diffuse and spherical nanoparticles. The cytotoxicity of PEG-PEI/siRNA nanocomplexes (N/P = 15) was significantly lower when compared with that of Lipofectamine 2000/siRNA (P < 0.05). Moreover, the highest transfection efficiency of PEG-PEI/siRNA nanoparticles was obtained at an N/P ratio of 15, which was better than that achieved in the transfection using Lipofectamine 2000 (P < 0.05). Finally, the gene knockdown effect of PEG-PEI/siRNA nanoparticles was verified at the levels of mRNA and protein. These results suggest that

  12. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function

    OpenAIRE

    Warde-Farley, David; Sylva L. Donaldson; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George

    2010-01-01

    GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis t...

  13. Greig cephalopolysyndactyly syndrome: Altered phenotype of a contiguous gene syndrome by the presence of a chromosomal deletion

    Energy Technology Data Exchange (ETDEWEB)

    Hersh, J.H.; Williams, P.G.; Yen, F.F. [Univ. of Louisville, KY (United States)] [and others

    1994-09-01

    Greig cephalopolysyndactyly syndrome (GCPS) is characterized by craniofacial anomalies, broad thumbs and halluces, polydactyly of the hands and feet, and variable syndactyly. Intellectual abilities are usually normal. Inheritance is in an autosomal dominant fashion. The disorder has been mapped to chromosome 7p13, suggesting that the condition represents a contiguous gene syndrome (CGS). A male infant presented with multiple congenital anomalies, including omphalocele, dysgenesis of the corpus callosum, hydrocephalus, esotropia, broad thumbs and halluces, syndactyly, polydactyly of one foot, hypotonia and developmental delay. A de novo interstitial deletion of chromosome 7p was detected, 46,XY,del(7)(p13p15). Although clinical findings in this case were reminiscent of GCPS, and the chromosomal abnormality included the region assigned to the candidate gene for this syndrome, additional physical abnormalities were present, as well as cognitive deficits. Some of these features have been previously described in patients with chromosomal deletions of 7p. The chromosomal abnormality in our case provides supportive evidence of the gene locus in GCPS, and that GCPS represents a new CGS. However, a larger deletion, extending beyond the limits of the gene, significantly altered the phenotype. Isolation of the gene responsible for GCPS, and identification of additional patients with chromosomal abnormalities in this region of chromosome 7, should help to provide more accurate genotype-phenotype correlations.

  14. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  15. [Is gene technology immoral?].

    Science.gov (United States)

    Halter, H

    1994-10-01

    Since it came into being in the USA in the early 1970s, gene technology has always been fundamentally controversial, especially in the German-speaking countries. The optimistic--or critical--supporters of gene technology are convinced that, in view of gene technology's not otherwise attainable advantages for human and animal health, for food production and other important aims, it would be ethically unacceptable to restrict to the minimum or even ban it. On the other hand, the radical critics are convinced that gene technology, in view of its anthropologically false starting-point, the questionable interests behind it, and above all its unforeseeable, serious negative implications for mankind and environment, is unacceptable on ethical grounds. Critical reflexion on these polarized arguments must start from the question why precisely gene technology is so controversial, and what are the criteria for ethical assessment. These reflexions presuppose that the prior judgement of gene technology as a technology in the ideological field is rooted in life attitudes, history and nature in general, and this is true not only of gene technology's opponents but also its supporters. It is thus a question of one ideology vs. another. Chief importance here attaches to the mankind-nature relationship and the need to take seriously the fundamental ambivalence of all (!) human action with unforeseeable consequences. The conclusion is that neither to demonize nor to glorify gene technology, as a matter of principle, does justice to its wide and varied positive or negative potential. The ethical assessment of gene technology must be differentiated according to the aims and possible implications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7939540

  16. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  17. High-resolution analysis of aberrant regions in autosomal chromosomes in human leukemia THP-1 cell line

    Directory of Open Access Journals (Sweden)

    Suzuki Takahiro

    2009-07-01

    Full Text Available Abstract Background THP-1 is a human monocytic leukemia cell line derived from a patient with acute monocytic leukemia. The cell line differentiates into macrophage-like cells by stimulation with phorbol myristate acetate (PMA. Although it has been used frequently as a model for macrophage differentiation in research including the FANTOM4/Genome Network Project, there are few reports on its genomic constitution. Therefore, we attempted to reveal the genomic aberrations in these cells with the microarray-based comparative genomic hybridization (aCGH technique. Findings We report large aberrations, including deletions 6p, 12p, 17p, and trisomy 8, and revealed breakpoints in the MLL and MLLT3 genes. Moreover, we found novel genomic aberrations such as a hemizygous narrow deletion partially containing the TP73 gene and homozygous deletions, including the CDKN2A, CDKN2B and PTEN genes. Conclusion In this study, we identified 119 aberrant regions in autosomal chromosomes, and at least 16 of these aberrations were less than 100 kb, most of which were undetectable in the previous works. We also revealed a total of 4.6 Mb of homozygous deleted regions. Our results will provide a base to precisely understand studies involving the THP-1 cell line, especially the huge amount of data generated from the FANTOM4/Genome Network Project.

  18. New common variants affecting susceptibility to basal cell carcinoma.

    Science.gov (United States)

    Stacey, Simon N; Sulem, Patrick; Masson, Gisli; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Jakobsdottir, Margret; Sigurdsson, Asgeir; Gudbjartsson, Daniel F; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Scherer, Dominique; Hemminki, Kari; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Botella-Estrada, Rafael; Soriano, Virtudes; Juberias, Pablo; Saez, Berta; Gilaberte, Yolanda; Fuentelsaz, Victoria; Corredera, Cristina; Grasa, Matilde; Höiom, Veronica; Lindblom, Annika; Bonenkamp, Johannes J; van Rossum, Michelle M; Aben, Katja K H; de Vries, Esther; Santinami, Mario; Di Mauro, Maria G; Maurichi, Andrea; Wendt, Judith; Hochleitner, Pia; Pehamberger, Hubert; Gudmundsson, Julius; Magnusdottir, Droplaug N; Gretarsdottir, Solveig; Holm, Hilma; Steinthorsdottir, Valgerdur; Frigge, Michael L; Blondal, Thorarinn; Saemundsdottir, Jona; Bjarnason, Hjördis; Kristjansson, Kristleifur; Bjornsdottir, Gyda; Okamoto, Ichiro; Rivoltini, Licia; Rodolfo, Monica; Kiemeney, Lambertus A; Hansson, Johan; Nagore, Eduardo; Mayordomo, José I; Kumar, Rajiv; Karagas, Margaret R; Nelson, Heather H; Gulcher, Jeffrey R; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Olafsson, Jon H; Kong, Augustine; Stefansson, Kari

    2009-08-01

    In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma. PMID:19578363

  19. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  20. What Is a Gene?

    Science.gov (United States)

    ... Quizzes Kids' Dictionary of Medical Words En Español What Other Kids Are Reading Back-to-School Butterflies? ... Got Homework? Here's Help White House Lunch Recipes What Is a Gene? KidsHealth > For Kids > What Is ...

  1. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  2. Effects of si-DNMT1 to Methylation of Tumor Suppressor Genes of Hilar Cholangiocarcinoma%si-DNMT1对肝门部胆管癌细胞抑癌基因甲基化的作用

    Institute of Scientific and Technical Information of China (English)

    向吉锋; 罗放; 王济明; 李修红

    2011-01-01

    Objective To study the effect of RNA interference on hypermethylation of tumor suppressor genes of hilar cholangiocarcinoma cell line QBC939,to explore its value in the treatment of rholangiocarcinoma. Methods hairpin siRNA expression vector targeting hDNMTl was constructed ,and then transfected into hilar cholangiocareinoma cell line QBC939 using liposome. The expression level of hDNMTl,CDH1 , pl5 was detected by RT-PCR at different time points. The methylation status of tumor suppressor genes CDH1 ,p15 was detected by MSP. The cell proliferation ability was detected by MTT. Results 1 ) Targeted gene knockout of hDNMTl restored the expression level of tumor suppressor genes CDH1 and pl5. 2 ) The expression silencing of CDH1 ,pl5 is caused by promoter hypermethylation. 3 ) Transfection with hairpin siR-NA plasmid expression vector targeting hDNMTl can effectively inhibit the cell proliferation ability of QBC939. Conclusion The transfection of hairpin siRNA plasmid expression vector targeting hDNMTl can play a effective,sustainable and stable role on gene silencing,and restore the expression level of tumor suppressor,thereby,inhibit the proliferation of QBC939.%目的 研究RNA干扰对肝门部胆管癌细胞株QBC939抑癌基因甲基化的影响,初步探讨其在胆管癌治疗中的价值.方法 构建靶向hDNMT1的发夹式siRNA表达载体;运用脂质体介导法将其转染人胆管癌细胞QBC939;RT-PCR法检测不同时间点hDNMT1、CDH1、p15的表达水平;MSP方法检测转染前后抑癌基因CDH1、p15的甲基化状态;MTT检测各组细胞的增殖能力.结果1) hDNMT1的基因沉默恢复了抑癌基因CDH1、p15的表达水平;2)CDH1、p15的表达沉默是由启动予高甲基化导致的;3)转染靶向hDNMT1的发夹式siRNA表达载体能有效地抑制QBC939的增殖能力.结论 靶向hDNMT1的发夹式siRNA表达载体能有效、持续、稳定发挥对hDNMT1的基因沉默作用,恢复抑癌基因CDH1、p15

  3. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  4. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin(IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha(TNF-α), C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

  5. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.;

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  6. Hox genes and study of Hox genes in crustacean

    Institute of Scientific and Technical Information of China (English)

    HOU Lin; CHEN Zhijuan; XU Mingyu; LIN Shengguo; WANG Lu

    2004-01-01

    Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

  7. GeneCards Version 3: the human gene integrator.

    Science.gov (United States)

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  8. GeneCards Version 3: the human gene integrator.

    Science.gov (United States)

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  9. TAGCNA: a method to identify significant consensus events of copy number alterations in cancer.

    Science.gov (United States)

    Yuan, Xiguo; Zhang, Junying; Yang, Liying; Zhang, Shengli; Chen, Baodi; Geng, Yaojun; Wang, Yue

    2012-01-01

    Somatic copy number alteration (CNA) is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs) from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4) and tumor suppressor genes (e.g. CDKN2A, CDKN2B), and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/. PMID:22815924

  10. Integrated analysis of germline and somatic variants in ovarian cancer.

    Science.gov (United States)

    Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles; McLellan, Michael D; Leiserson, Mark D M; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F; Wyczalkowski, Matthew A; Larson, David E; Schmidt, Heather K; Miller, Christopher A; Fulton, Robert S; Spellman, Paul T; Mardis, Elaine R; Druley, Todd E; Graubert, Timothy A; Goodfellow, Paul J; Raphael, Benjamin J; Wilson, Richard K; Ding, Li

    2014-01-01

    We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways. PMID:24448499

  11. TAGCNA: a method to identify significant consensus events of copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Xiguo Yuan

    Full Text Available Somatic copy number alteration (CNA is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4 and tumor suppressor genes (e.g. CDKN2A, CDKN2B, and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/.

  12. Gene therapy for brain tumors.

    Science.gov (United States)

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  13. Introns in higher plant genes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The intron is an important component of eukaryotic gene. Extensive studies have been conducted to get a better understanding of its structure and function. This paper presents a brief review of the structure and function of introns in higher plant genes. It is shown that higher plant introns possess structural properties shared by all eukaryotic introns, however, they also exhibit a striking degree of diversity. The process of intron splicing in higher plant genes involves interaction between multiple cis-acting elements and trans-acting factors, such as 5′ splicing site, 3′ splicing site and many protein factors. The process of intron splicing is an important level at which gene expression is regulated. Especially alternative splicing of intron can regulate time and space of gene expression. In addition, some introns in higher plant genes also regulate gene expression by affecting the pattern of gene expression, enhancing the level of gene expression and driving the gene expression.

  14. Association between common germline genetic variation in 94 candidate genes or regions and risks of invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Quaye, Lydia; Tyrer, Jonathan; Ramus, Susan J;

    2009-01-01

    BACKGROUND: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant....... To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA. RESULTS: After adjusting for population stratification by genomic...... control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide...

  15. Radionuclide reporter gene imaging for cardiac gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Inubushi, Masayuki [Hokkaido University Graduate School of Medicine, Department of Molecular Imaging, Sapporo (Japan); Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan)

    2007-06-15

    In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)

  16. A review on microcephaly genes

    Directory of Open Access Journals (Sweden)

    Irshad S.

    2012-06-01

    Full Text Available This review aims to summarize the recent findings regarding microcephaly genes. We have discussed the molecular genetics studies of microcephaly genes including a comprehensive appraisal of the seven mapped loci (MCPH1–MCPH7, their corresponding genes and protein products of the genes, their likely role in normal brain development and the details of the mutations reported in these genes.

  17. Gene therapy: progress and predictions

    OpenAIRE

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of ...

  18. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  19. Correlating Expression Data with Gene Function Using Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    LIU,Qi; DENG,Yong; WANG,Chuan; SHI,Tie-Liu; LI,Yi-Xue

    2006-01-01

    Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions.However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.

  20. The gene tree delusion.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  1. The gene tree delusion.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  2. Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes

    Directory of Open Access Journals (Sweden)

    Rolf I. Skotheim

    2006-01-01

    Full Text Available Introduction: Testicular germ cell tumors of adolescent and young adult men (TGCTs generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified. Materials and Methods: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH, and integrated the data with transcriptome profiles of the same samples. Results: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes. Conclusion: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.

  3. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong;

    2003-01-01

    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistently...... low false-negative rate. The incorporation of similarity information is meant to reduce the false-positive rate, but in doing so it increases the false-negative rate. The crucial variable is gene size (including introns)--genes of the most extreme sizes, especially very large genes, are most likely to...

  4. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  5. GENES BEHIND SMOKE ACTION

    Directory of Open Access Journals (Sweden)

    Vilmos Soós

    2008-09-01

    Full Text Available Smoke can break dormancy and promote seed germination of many plant species. We investigated changes in the gene expression changes after imbibition of light-sensitive Lactuca sativa L. cv. Grand Rapids achenes with dilute smoke water compared to water control samples kept in dark or continuous light. Although no difference was detected in the smoke water vs. water control samples germinated in light, smoke water treatment resulted in the differential display of several expressed sequence tags (ESTs when compared to water control samples kept in dark. The most pronounced fragments isolated correspond to known genes with functions related to cell wall expansion, abscisic acid regulation, regulation of translation, the cell division cycle, carbohydrate metabolism and desiccation tolerance. These data clearly indicate that the smoke water, which stimulates germination of light-sensitive Grand Rapids lettuce seeds in the dark, rapidly affects genes that are essential for cell division, cell wall expansion and mobilization and utilization of nutrients for the resumption of embryo growth. Although the master genes remained unknown, our hope is that the using of maize microarray will reveal the whole molecular background of smoke action.

  6. Ultrasound mediated gene transfection

    Science.gov (United States)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

    2002-05-01

    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  7. Old genes experience stronger translational selection than young genes.

    Science.gov (United States)

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. PMID:27259662

  8. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  9. Industrial scale gene synthesis.

    Science.gov (United States)

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery.

  10. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V;

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  11. Entrez Gene: gene-centered information at NCBI.

    Science.gov (United States)

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2007-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp. PMID:17148475

  12. Tumor-specific gene expression patterns with gene expression profiles

    Institute of Scientific and Technical Information of China (English)

    RUAN Xiaogang; LI Yingxin; LI Jiangeng; GONG Daoxiong; WANG Jinlian

    2006-01-01

    Gene expression profiles of 14 common tumors and their counterpart normal tissues were analyzed with machine learning methods to address the problem of selection of tumor-specific genes and analysis of their differential expressions in tumor tissues. First, a variation of the Relief algorithm, "RFE_Relief algorithm" was proposed to learn the relations between genes and tissue types. Then, a support vector machine was employed to find the gene subset with the best classification performance for distinguishing cancerous tissues and their counterparts. After tissue-specific genes were removed, cross validation experiments were employed to demonstrate the common deregulated expressions of the selected gene in tumor tissues. The results indicate the existence of a specific expression fingerprint of these genes that is shared in different tumor tissues, and the hallmarks of the expression patterns of these genes in cancerous tissues are summarized at the end of this paper.

  13. Phylogenetic analysis of VP2 gene of canine parvovirus and comparison with Indian and world isolates.

    Science.gov (United States)

    Kaur, G; Chandra, M; Dwivedi, P N

    2016-03-01

    Canine parvovirus (CPV) causes hemorrhagic enteritis, especially in young dogs, leading to high morbidity and mortality. It has four main antigenic types CPV-2, CPV-2a, CPV-2b and CPV-2c. Virus protein 2 (VP2) is the main capsid protein and mutations affecting VP2 gene are responsible for the evolution of various antigenic types of CPV. Full length VP2 gene from field isolates was amplified and cloned for sequence analysis. The sequences were submitted to the GenBank and were assigned Acc. Nos., viz. KP406928.1 for P12, KP406927.1 for P15, KP406930.1 for P32, KP406926.1 for Megavac-6 and KP406929.1 for NobivacDHPPi. Phylogenetic analysis indicated that the samples were forming a separate clad with vaccine strains. When the samples were compared with the world and Indian isolates, it was observed that samples formed a separate node indicating regional genetic variation in CPV.

  14. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  15. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  16. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Odelta dos Santos

    Full Text Available Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR, one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  17. Dominance from the perspective of gene-gene and gene-chemical interactions.

    Science.gov (United States)

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe. PMID:26613610

  18. Dominance from the perspective of gene-gene and gene-chemical interactions.

    Science.gov (United States)

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.

  19. Gene doping in modern sport.

    Directory of Open Access Journals (Sweden)

    MAREK SAWCZUK

    2009-01-01

    Full Text Available Background: The subject of this paper is gene doping, which should be understood as "he non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". The authors of this work, based on the review of literature and previous research, make an attempt at wider characterization of gene doping and the discussion of related potential threats.Methods: This is a comprehensive survey of literature on the latest applications of molecular biology in medicine. The analysis involves a dozen scientific databases examined in order to find genes used in gene therapy and potentially useful in gene doping. Results: The obtained results enable better recognition of gene doping and indicate genes used in medicine that could be used in gene doping. This paper describes potential effects of their use and associated risk, and predicts the possible developments of gene doping in the future. Conclusion: Gene doping is undoubtedly a part of modern sport. Although WADA included gene doping on the list of banned methods as early as 2004, as previously stated above, it has not managed to develop efficient methods of detection.

  20. High-resolution Whole-Genome Analysis of Skull Base Chordomas Implicates FHIT Loss in Chordoma Pathogenesis

    Directory of Open Access Journals (Sweden)

    Roberto Jose Diaz

    2012-09-01

    Full Text Available Chordoma is a rare tumor arising in the sacrum, clivus, or vertebrae. It is often not completely resectable and shows a high incidence of recurrence and progression with shortened patient survival and impaired quality of life. Chemotherapeutic options are limited to investigational therapies at present. Therefore, adjuvant therapy for control of tumor recurrence and progression is of great interest, especially in skull base lesions where complete tumor resection is often not possible because of the proximity of cranial nerves. To understand the extent of genetic instability and associated chromosomal and gene losses or gains in skull base chordoma, we undertook whole-genome single-nucleotide polymorphism microarray analysis of flash frozen surgical chordoma specimens, 21 from the clivus and 1 from C1 to C2 vertebrae. We confirm the presence of a deletion at 9p involving CDKN2A, CDKN2B, and MTAP but at a much lower rate (22% than previously reported for sacral chordoma. At a similar frequency (21%, we found aneuploidy of chromosome 3. Tissue microarray immunohistochemistry demonstrated absent or reduced fragile histidine triad (FHIT protein expression in 98% of sacral chordomas and 67%of skull base chordomas. Our data suggest that chromosome 3 aneuploidy and epigenetic regulation of FHIT contribute to loss of the FHIT tumor suppressor in chordoma. The finding that FHIT is lost in a majority of chordomas provides new insight into chordoma pathogenesis and points to a potential new therapeutic target for this challenging neoplasm.

  1. Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung

    Directory of Open Access Journals (Sweden)

    Alexander Salskov

    2011-01-01

    Full Text Available It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%, CCND2 (21%, CDH1 (7%, and RARB (4% were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26% than in never-smokers (3%. CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41% and never-smokers (30%. BVES, CDH13, CDKN2A (p16, CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2% in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung.

  2. Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Jasmine Healy

    2010-01-01

    Full Text Available Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL. We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P=.017 and CDKN2B rs36229158 (P=.022 that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases.

  3. The gene coding for PGC-1α modifies age at onset in Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Oberkofler Hannes

    2009-01-01

    Full Text Available Abstract Huntington's disease (HD is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT, localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1α, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1α. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1α system on the course of Huntington's disease in humans.

  4. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    Science.gov (United States)

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  5. On atavisms and atavistic genes.

    Science.gov (United States)

    Cantú, J M; Ruiz, C

    1985-01-01

    The authors propose the term atavistic to designate a gene producing an ancestral phenotype (atavism). Several examples are presented, and the possible origin of atavistic genes, as well as their pathological implications discussed. PMID:3879145

  6. Genes That Influence Blood Pressure

    Science.gov (United States)

    ... Research Matters NIH Research Matters September 26, 2011 Genes that Influence Blood Pressure In one of the ... 16 previously unknown variations. Six were found in genes already suspected of regulating blood pressure. The remaining ...

  7. Genes and human brain evolution

    OpenAIRE

    Geschwind, Daniel H.; Konopka, Genevieve

    2012-01-01

    Several genes were duplicated during human evolution. It seems that one such duplication gave rise to a gene that may have helped to make human brains bigger and more adaptable than those of our ancestors.

  8. Gene Testing for Hereditary Ataxia

    Science.gov (United States)

    FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Gene Testing for Hereditary Ataxia This fact sheet provides an overview of gene testing for ataxia. It also addresses commonly asked ...

  9. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  10. Human housekeeping genes are compact

    OpenAIRE

    Eisenberg, Eli; Erez Y. Levanon

    2003-01-01

    We identify a set of 575 human genes that are expressed in all conditions tested in a publicly available database of microarray results. Based on this common occurrence, the set is expected to be rich in "housekeeping" genes, showing constitutive expression in all tissues. We compare selected aspects of their genomic structure with a set of background genes. We find that the introns, untranslated regions and coding sequences of the housekeeping genes are shorter, indicating a selection for co...

  11. Gene therapy of liver cancer

    OpenAIRE

    Hernandez-Alcoceba, R. (Rubén); B. Sangro; Prieto, J.

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reac...

  12. Genes y especies

    Directory of Open Access Journals (Sweden)

    A. G. Sáez

    2009-01-01

    Full Text Available La posibilidad de secuenciar y manipular los genes sigue abriendo fronteras en el estudio de las especies y la especiación. En tiempos recientes particularmente en dos direcciones. Por un lado, la secuenciación del gen COI (y otros en miles de muestras de forma sistemática y masiva, el llamado "DNA barcoding", está revelando una gran cantidad de biodiversidad, en buena medida previamente no sospechada y correspondiente a especies crípticas (morfológicamente irreconocibles. En segundo lugar, el estudio de los genes responsables de los cambios morfológicos nos está haciendo volver a dar una creciente importancia a la selección como motor de la especiación y de la evolución, incluso en presencia de dosis importantes de flujo génico.

  13. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  14. Gene therapy for mucopolysaccharidosis

    OpenAIRE

    Ponder, Katherine P.; Haskins, Mark E.

    2007-01-01

    Mucopolysaccharidoses (MPS) are due to deficiencies in activities of lysosomal enzymes that degrade glycosaminoglycans. Some attempts at gene therapy for MPS in animal models have involved intravenous injection of vectors derived from an adeno-associated virus (AAV), adenovirus, retrovirus or a plasmid, which primarily results in expression in liver and secretion of the relevant enzyme into blood. Most vectors can correct disease in liver and spleen, although correction in other organs includ...

  15. Engineering prokaryotic gene circuits

    OpenAIRE

    Michalodimitrakis, Konstantinos; Isalan, Mark

    2009-01-01

    Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, t...

  16. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  17. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  18. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  19. Ascidian gene-expression profiles

    OpenAIRE

    William R Jeffery

    2002-01-01

    With the advent of gene-expression profiling, a large number of genes can now be investigated simultaneously during critical stages of development. This approach will be particularly informative in studies of ascidians, basal chordates whose genomes and embryology are uniquely suited for mapping developmental gene networks.

  20. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin;

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  1. Decationized polyplexes for gene delivery

    NARCIS (Netherlands)

    Novo, L.; Mastrobattista, E.; Nostrum, van C.F.; Lammers, T.G.G.M.; Hennink, W.E.

    2015-01-01

    Gene therapy has received much attention in the field of drug delivery. Synthetic, nonviral gene delivery systems have gained increasing attention as vectors for gene therapy mainly due to a favorable immunogenicity profile and ease of manufacturing as compared to viral vectors. The great majority o

  2. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  3. Gene therapy for thyroid cancer

    International Nuclear Information System (INIS)

    Gene therapy for thyroid cancer include immunotherapy, suicide gene therapy, tumor suppressor replacement, 131I therapy by sodium/iodide symporter and antisense therapy and so on. Gene therapy has wide perspectives, but there are many problems need to be solved for clinical application

  4. nanosheets for gene therapy

    Science.gov (United States)

    Kou, Zhongyang; Wang, Xin; Yuan, Renshun; Chen, Huabin; Zhi, Qiaoming; Gao, Ling; Wang, Bin; Guo, Zhaoji; Xue, Xiaofeng; Cao, Wei; Guo, Liang

    2014-10-01

    A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.

  5. Extracting gene-gene interactions through curve fitting.

    Science.gov (United States)

    Das, Ranajit; Mitra, Sushmita; Murthy, C A

    2012-12-01

    This paper presents a simple and novel curve fitting approach for generating simple gene regulatory subnetworks from time series gene expression data. Microarray experiments simultaneously generate massive data sets and help immensely in the large-scale study of gene expression patterns. Initial biclustering reduces the search space in the high-dimensional microarray data. The least-squares error between fitting of gene pairs is minimized to extract a set of gene-gene interactions, involving transcriptional regulation of genes. The higher error values are eliminated to retain only the strong interacting gene pairs in the resultant gene regulatory subnetwork. Next the algorithm is extended to a generalized framework to enhance its capability. The methodology takes care of the higher-order dependencies involving multiple genes co-regulating a single gene, while eliminating the need for user-defined parameters. It has been applied to the time-series Yeast data, and the experimental results biologically validated using standard databases and literature. PMID:22997274

  6. Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism

    OpenAIRE

    Ma, D Q; Whitehead, P. L.; Menold, M M; Martin, E. R.; Ashley-Koch, A. E.; Mei, H; Ritchie, M. D.; Delong, G R; Abramson, R.K.; Wright, H. H.; Cuccaro, M. L.; Hussman, J. P.; Gilbert, J.R.; Pericak-Vance, M A

    2005-01-01

    Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied...

  7. Gene Network Biological Validity Based on Gene-Gene Interaction Relevance

    OpenAIRE

    Francisco Gómez-Vela; Norberto Díaz-Díaz

    2014-01-01

    In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in...

  8. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  9. Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

    Science.gov (United States)

    Lachance, Daniel H; Yang, Ping; Johnson, Derek R; Decker, Paul A; Kollmeyer, Thomas M; McCoy, Lucie S; Rice, Terri; Xiao, Yuanyuan; Ali-Osman, Francis; Wang, Frances; Stoddard, Shawn M; Sprau, Debra J; Kosel, Matthew L; Wiencke, John K; Wiemels, Joseph L; Patoka, Joseph S; Davis, Faith; McCarthy, Bridget; Rynearson, Amanda L; Worra, Joel B; Fridley, Brooke L; O'Neill, Brian Patrick; Buckner, Jan C; Il'yasova, Dora; Jenkins, Robert B; Wrensch, Margaret R

    2011-09-01

    Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997-2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76, 95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma. PMID:21742680

  10. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  11. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  12. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... Willi syndrome. PDF version of this page (220K) Gene sequence Genome view see gene locations Entrez Gene ...

  13. Gene Therapy and Children (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Gene Therapy and Children KidsHealth > For Parents > Gene Therapy ... that don't respond to conventional therapies. About Genes Our genes help make us unique. Inherited from ...

  14. Genes and species

    OpenAIRE

    Sáez, Alberto G.

    2009-01-01

    La posibilidad de secuenciar y manipular los genes sigue abriendo fronteras en el estudio de las especies y la especiación. En tiempos recientes particularmente en dos direcciones. Por un lado, la secuenciación del gen COI (y otros) en miles de muestras de forma sistemática y masiva, el llamado "DNA barcoding", está revelando una gran cantidad de biodiversidad, en buena medida previamente no sospechada y correspondiente a especies crípticas (morfológicamente irreconocibles). En segundo lug...

  15. Computation in gene networks

    Science.gov (United States)

    Ben-Hur, Asa; Siegelmann, Hava T.

    2004-03-01

    Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.

  16. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  17. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function.

    Science.gov (United States)

    Warde-Farley, David; Donaldson, Sylva L; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George; Bader, Gary D; Morris, Quaid

    2010-07-01

    GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. PMID:20576703

  18. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  19. PROAPOPTOTIC FUNCTION OF FHIT GENE

    Institute of Scientific and Technical Information of China (English)

    QIU Zhe-fu; HAN De-min; ZHANG Luo; ZHANG Wei

    2006-01-01

    Tumor suppressor gene plays an important role in maintaining the homeostasis between cell loss and growth. Fragile in maintaining the homeostasis between cell loss and growth. Fragile histidine triad (FHIT) gene found recently was studied in a deep going way; it becomes the focus as a result of its roleof ep going way; it becomes the focus as a result of its roleof anti-tumor in human various type of tissue. Due to the high efficiency of FHIT gene benefiting the anti-tumor, it is proposed gh efficiency of FHIT gene benefiting the anti-tumor, it is proposed as a candidate of tumor suppressor gene though there are several opposite opinions.several opposite opinions. We stress the summary of some properties of FHIT gene on proapoptosis according to the published data which showed gene on proapoptosis according to the published data which showed the stronger proapoptotic function of FHIT gene; the apoptosis induced by FHIT depends on the expression level and status of ene; the apoptosis induced by FHIT depends on the expression level and status of FHIT; and FHIT gene can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process e can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process induced by FHIT has no relation to p53 gene. In a ward, in consideration of its multiple functions against malignancies, FHIT in consideration of its multiple functions against malignancies, FHIT gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical et for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.le histidine triad (FHIT) gene; Apoptosis; Tumorigenesis; Tumor suppressor gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.

  20. Identifying Driver Genes in Cancer by Triangulating Gene Expression, Gene Location, and Survival Data

    Science.gov (United States)

    Rouam, Sigrid; Miller, Lance D; Karuturi, R Krishna Murthy

    2014-01-01

    Driver genes are directly responsible for oncogenesis and identifying them is essential in order to fully understand the mechanisms of cancer. However, it is difficult to delineate them from the larger pool of genes that are deregulated in cancer (ie, passenger genes). In order to address this problem, we developed an approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic intersects). Here, we present a refinement of this approach incorporating a new scoring methodology to identify putative driver genes that are deregulated in cancer. TRIAGE triangulates – or integrates – three levels of information: gene expression, gene location, and patient survival. First, TRIAGE identifies regions of deregulated expression (ie, expression footprints) by deriving a newly established measure called the Local Singular Value Decomposition (LSVD) score for each locus. Driver genes are then distinguished from passenger genes using dual survival analyses. Incorporating measurements of gene expression and weighting them according to the LSVD weight of each tumor, these analyses are performed using the genes located in significant expression footprints. Here, we first use simulated data to characterize the newly established LSVD score. We then present the results of our application of this refined version of TRIAGE to gene expression data from five cancer types. This refined version of TRIAGE not only allowed us to identify known prominent driver genes, such as MMP1, IL8, and COL1A2, but it also led us to identify several novel ones. These results illustrate that TRIAGE complements existing tools, allows for the identification of genes that drive cancer and could perhaps elucidate potential future targets of novel anticancer therapeutics. PMID:25949096

  1. Genes of aging.

    Science.gov (United States)

    Hamet, Pavel; Tremblay, Johanne

    2003-10-01

    According to developmental genetics theories, aging is a genetically programmed and controlled continuum of development and maturation. Being dynamic and malleable processes, development and aging are controlled not only by genes but also by environmental and epigenetic influences that predominate in the second half of life. Genetic mutations affect many phenotypes in flies, worms, rodents, and humans which share several diseases or their equivalents, including cancer, neurodegeneration, and infectious disorders as well as their susceptibility to them. Life span and stress resistance are closely linked. Oxidative stress actually constitutes a defined hypothesis of aging in that macromolecule oxidative damage accumulates with age and tends to be associated with life expectancy. DNA methylation, a force in the regulation of gene expression, is also one of the biomarkers of genetic damage. The mitotic clock of aging is marked, if not guided, by telomeres, essential genetic elements stabilizing natural chromosomic ends. The dream of humans to live longer, healthy lives is being tested by attempts to modify longevity in animal models, frequently by dietary manipulation. The quest continues to understand the mechanisms of healthy aging, one of the most compelling areas of research in the 21st century. PMID:14577056

  2. Tetraspanin genes in plants.

    Science.gov (United States)

    Wang, Feng; Vandepoele, Klaas; Van Lijsebettens, Mieke

    2012-07-01

    Tetraspanins represent a four-transmembrane protein superfamily with a conserved structure and amino acid residues that are present in mammals, insects, fungi and plants. Tetraspanins interact with each other or with other membrane proteins to form tetraspanin-enriched microdomains that play important roles in development, pathogenesis and immune responses via facilitating cell-cell adhesion and fusion, ligand binding and intracellular trafficking. Here, we emphasize evolutionary aspects within the plant kingdom based on genomic sequence information. A phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed ancient and fast evolving clades. Tetraspanins were only present in multicellular plants, were often duplicated in the plant genomes and predicted by the electronic Fluorescent Pictograph for gene expression analysis to be either functionally redundant or divergent. Tetraspanins contain a large extracellular loop with conserved cysteines that provide the binding sites for the interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal proteome, suggesting a role in cell-cell communication during plant development.

  3. Immunity-related genes and gene families in Anopheles gambiae.

    Science.gov (United States)

    Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C

    2002-10-01

    We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. PMID:12364793

  4. Gene-targeting pharmaceuticals for single-gene disorders.

    Science.gov (United States)

    Beaudet, Arthur L; Meng, Linyan

    2016-04-15

    The concept of orphan drugs for treatment of orphan genetic diseases is perceived enthusiastically at present, and this is leading to research investment on the part of governments, disease-specific foundations and industry. This review attempts to survey the potential to use traditional pharmaceuticals as opposed to biopharmaceuticals to treat single-gene disorders. The available strategies include the use of antisense oligonucleotides (ASOs) to alter splicing or knock-down expression of a transcript, siRNAs to knock-down gene expression and drugs for nonsense mutation read-through. There is an approved drug for biallelic knock-down of the APOB gene as treatment for familial hypercholesterolemia. Both ASOs and siRNAs are being explored to knock-down the transthyretin gene to prevent the related form of amyloidosis. The use of ASOs to alter gene-splicing to treat spinal muscular atrophy is in phase 3 clinical trials. Work is progressing on the use of ASOs to activate the normally silent paternal copy of the imprinted UBE3A gene in neurons as a treatment for Angelman syndrome. A gene-activation or gene-specific ramp-up strategy would be generally helpful if such could be developed. There is exciting theoretical potential for converting biopharmaceutical strategies such gene correction and CRISPR-Cas9 editing to a synthetic pharmaceutical approach. PMID:26628634

  5. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer

    Directory of Open Access Journals (Sweden)

    Pistey Robert

    2008-03-01

    Full Text Available Abstract Background CDKN1C (also known as p57KIP2 is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1 have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. Methods We determined rates of allele imbalance or loss of heterozygosity (AI/LOH in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR, and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC. All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. Results AI/LOH at 11p15.5 occurred in 28/73 (38% informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19% cancers (p = ns. In contrast, CDKN1C mRNA levels were reduced in 9/10 (90% cancers (p Conclusion CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.

  6. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    Energy Technology Data Exchange (ETDEWEB)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  7. Gene polymorphisms in chronic periodontitis

    OpenAIRE

    Laine, Marja L; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in ...

  8. Hormones, genes, and behavior

    OpenAIRE

    Pfaff, Donald W.

    1997-01-01

    With assays of hormone-sensitive behaviors, it is possible to demonstrate both direct and indirect actions of genes on mammalian social behaviors. Direct effects of estrogen receptor gene expression and progesterone receptor gene expression figure prominently in well analyzed neuroendocrine mechanisms for sex behavior, operating through a neural circuit that has been delineated. Indirect effects, notably the consequences of sexual differentiation, display complex d...

  9. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  10. Gene therapy in pancreatic cancer

    OpenAIRE

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-01-01

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC...

  11. Testing for gene-gene interaction with AMMI models.

    Science.gov (United States)

    Barhdadi, Amina; Dubé, Marie-Pierre

    2010-01-01

    Studies have shown that many common diseases are influenced by multiple genes and their interactions. There is currently a strong interest in testing for association between combinations of these genes and disease, in particular because genes that affect the risk of disease only in the presence of another genetic variant may not be detected in marginal analysis. In this paper we propose the use of additive main effect and multiplicative interaction (AMMI) models to detect and to quantify gene-gene interaction effects for a quantitative trait. The objective of the present research is to demonstrate the practical advantages of these models to describe complex interaction between two unlinked loci. Although gene-gene interactions have often been defined as a deviance from additive genetic effects, the residual term has generally not been appropriately treated. The AMMI models allow for the analysis of a two way factorial data structure and combine the analysis of variance of the two main genotype effects with a principal component analysis of the residual multiplicative interaction. The AMMI models for gene-gene interaction presented here allow for the testing of non additivity between the two loci, and also describe how their interaction structure fits the existing non-additivity. Moreover, these models can be used to identify the specific two genotypes combinations that contribute to the significant gene-gene interaction. We describe the use of the biplot to display the structure of the interaction and evaluate the performance of the AMMI and the special cases of the AMMI previously described by Tukey and Mandel with simulated data sets. Our simulated study showed that the AMMI model is as powerful as general linear models when the interaction is not modeled in the presence of marginal effects. However, in the presence of pure epitasis, i.e. in the absence of marginal effects, the AMMI method was not found to be superior to other tested regression methods.

  12. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK

    2010-10-01

    Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

  13. ERGDB: Estrogen Responsive Genes Database.

    Science.gov (United States)

    Tang, Suisheng; Han, Hao; Bajic, Vladimir B

    2004-01-01

    ERGDB is an integrated knowledge database dedicated to genes responsive to estrogen. Genes included in ERGDB are those whose expression levels are experimentally proven to be either up-regulated or down-regulated by estrogen. Genes included are identified based on publications from the PubMed database and each record has been manually examined, evaluated and selected for inclusion by biologists. ERGDB aims to be a unified gateway to store, search, retrieve and update information about estrogen responsive genes. Each record contains links to relevant databases, such as GenBank, LocusLink, Refseq, PubMed and ATCC. The unique feature of ERGDB is that it contains information on the dependence of gene reactions on experimental conditions. In addition to basic information about the genes, information for each record includes gene functional description, experimental methods used, tissue or cell type, gene reaction, estrogen exposure time and the summary of putative estrogen response elements if the gene's promoter sequence was available. Through a web interface at http://sdmc.i2r.a-star.edu.sg/ergdb/ cgi-bin/explore.pl users can either browse or query ERGDB. Access is free for academic and non-profit users. PMID:14681475

  14. Deletions in chromosome 4 differentially associated with the development of cervical cancer: evidence of slit2 as a candidate tumor suppressor gene.

    Science.gov (United States)

    Singh, Ratnesh Kumar; Indra, Dipanjana; Mitra, Sraboni; Mondal, Ranajit Kumar; Basu, Partha Sarathi; Roy, Anup; Roychowdhury, Susanta; Panda, Chinmay Kumar

    2007-08-01

    The aim of this study was to locate the candidate tumor suppressor genes (TSGs) loci in the chromosomal 4p15-16, 4q22-23 and 4q34-35 regions associated with the development of uterine cervical carcinoma (CA-CX). Deletion mapping of the regions by microsatellite markers identified six discrete areas with high frequency of deletions, viz. 4p16.2 (D1: 40%), 4p15.31 (D2: 35-38%), 4p15.2 (D3: 37-40%), 4q22.2 (D4: 34%), 4q34.2-34.3 (D5: 37-59%) and 4q35.1 (D6: 40-50%). Significant correlation was noted among the deleted regions D1, D2 and D3. The deletions in D1, D2, D5 and D6 regions are suggested to be associated with the cervical intraepithelial neoplasia (CIN), and deletions in the D2, D3, D5 and D6 regions seems to be associated with progression of CA-CX. The deletions in the D2 and D6 regions showed significant prognostic implications (P = 0.001; 0.02). The expression of the candidate TSG SLIT2 mapped to D2 region gradually reduced from normal cervix uteri -->CIN --> CA-CX. SLIT2 promoter hypermethylation was seen in 28% CIN samples and significantly increased with tumor progression (P = 0.04). Significant correlation was seen between SLIT2 deletion and its promoter methylation (P = 0.001), indicating that both these phenomena could occur simultaneously to inactivate this gene. Immunohistochemical analysis showed reduced expression of SLIT2 in cervical lesions and CA-CX cell lines. Although no mutation was detected in the SLIT2 promoter region (-432 to + 55 bp), CC and AA haplotypes were seen in -227 and -195 positions, respectively. Thus, it indicates that inactivation of SLIT2-ROBO1 signaling pathway may have an important role in CA-CX development.

  15. Gene-environment interaction.

    Science.gov (United States)

    Manuck, Stephen B; McCaffery, Jeanne M

    2014-01-01

    With the advent of increasingly accessible technologies for typing genetic variation, studies of gene-environment (G×E) interactions have proliferated in psychological research. Among the aims of such studies are testing developmental hypotheses and models of the etiology of behavioral disorders, defining boundaries of genetic and environmental influences, and identifying individuals most susceptible to risk exposures or most amenable to preventive and therapeutic interventions. This research also coincides with the emergence of unanticipated difficulties in detecting genetic variants of direct association with behavioral traits and disorders, which may be obscured if genetic effects are expressed only in predisposing environments. In this essay we consider these and other rationales for positing G×E interactions, review conceptual models meant to inform G×E interpretations from a psychological perspective, discuss points of common critique to which G×E research is vulnerable, and address the role of the environment in G×E interactions.

  16. Angiogenin gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Dongsheng Fan; Yingshuang Zhang

    2013-01-01

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se-quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mel itus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa-tients) and 268 healthy controls. Al subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistical y significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  17. Genomic imbalances in esophageal carcinoma cell lines involve Wnt pathway genes

    Institute of Scientific and Technical Information of China (English)

    Jacqueline Brown; Hannelie Bothma; Robin Veale; Pascale Willem

    2011-01-01

    AIM: To identify molecular markers shared across South African esophageal squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy number analysis. METHODS: We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software. RESULTS: We detected common translocation breakpoints involving chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or interruption of the EPHA3 gene. The most significant amplifications involved the following chromosomal regions and genes: 11q13.3 ( CCND1, FGF3, FGF4, FGF19, MYEOV), 8q24.21( C-MYC, FAM84B), 11q22.1-q22.3 ( BIRC2, BIRC3), 5p15.2 ( CTNND2), 3q11.2-q12.2 ( MINA) and 18p11.32 ( TYMS, YES1). The significant deletions included 1p31.2-p31.1 ( CTH, GADD45α, DIRAS3), 2q22.1 ( LRP1B), 3p12.1-p14.2 ( FHIT), 4q22.1-q32.1 ( CASP6, SMAD1), 8p23.2-q11.1 ( BNIP3L) and 18q21.1-q21.2 ( SMAD4, DCC). The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC. CONCLUSION: The finding that a significant number of genes that were amplified (FGF3 , FGF4 , FGF19 , CCND1 and C-MYC ) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.

  18. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne;

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  19. Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis

    Directory of Open Access Journals (Sweden)

    Zhang Lisheng

    2002-11-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC presents one of the major health threats in China today. A better understanding of the molecular genetics underlying malignant transformation of hepatocytes is critical to success in the battle against this disease. The methylation state of C5 of the cytosine in the CpG di-nucleotide that is enriched within or near the promoter region of over 50 % of the polymerase II genes has a drastic effect on transcription of these genes. Changes in the methylation profile of the promoters represent an alternative to genetic lesions as causative factors for the tumor-specific aberrant expression of the genes. Methods We have used the methylation specific PCR method in conjunction with DNA sequencing to assess the methylation state of the promoter CpG islands of twenty genes. Aberrant expression of these genes have been attributed to the abnormal methylation profile of the corresponding promoter CpG islands in human tumors. Results While the following sixteen genes remained the unmethylated in all tumor and normal tissues: CDH1, APAF1, hMLH1, BRCA1, hTERC, VHL, RARβ, TIMP3, DAPK1, SURVIVIN, p14ARF, RB1, p15INK4b, APC, RASSF1c and PTEN, varying degrees of tumor specific hypermethylation were associated with the p16INK4a , RASSF1a, CASP8 and CDH13 genes. For instance, the p16INK4a was highly methylated in HCC (17/29, 58.6% and less significantly methylated in non-cancerous tissue (4/29. 13.79%. The RASSF1a was fully methylated in all tumor tissues (29/29, 100%, and less frequently methylated in corresponding non-cancerous tissue (24/29, 82.75%. Conclusions Furthermore, co-existence of methylated with unmethylated DNA in some cases suggested that both genetic and epigenetic (CpG methylation mechanisms may act in concert to inactivate the p16INK4a and RASSF1a in HCC. Finally, we found a significant association of cirrhosis with hypermethylation of the p16INK4a and hypomethylation of the CDH13 genes. For the

  20. STATE-OF-THE-ART HUMAN GENE THERAPY: PART I. GENE DELIVERY TECHNOLOGIES

    OpenAIRE

    Wang, Dan; Gao, Guangping

    2014-01-01

    Safe and effective gene delivery is a prerequisite for successful gene therapy. In the early age of human gene therapy, setbacks due to problematic gene delivery vehicles plagued the exciting therapeutic outcome. However, gene delivery technologies rapidly evolved ever since. With the advancement of gene delivery techniques, gene therapy clinical trials surged during the past decade. As the first gene therapy product has obtained regulatory approval and reached clinic, human gene therapy fina...

  1. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  2. A study on tumor suppressor genes mutations associated with different pathological colorectal lesions

    International Nuclear Information System (INIS)

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the Western world. In Egypt; there is an increasing incidence of the disease, especially among patients ≤40 years age. While CRC have been reported in low incidence rate in developing countries, it is the third most common tumor in male and the fifth common tumor in females in Egypt. Early diagnosis and surgical interference guarantee long survival of most CRC patients. Early diagnosis is impeded by the disease onset at young age and imprecise symptoms at the initial stages of the disease. As in most solid tumors, the malignant transformation of colonic epithelial cells is to arise through a multistep process during which they acquire genetic changes involving the activation of proto-oncogenes and the loss of tumor suppressor genes. Recently, a candidate tumor suppressor gene, KLF6, which is mapped to chromosome 10p, was found to be frequently mutated in a number of cancers. There are some evidences suggesting that the disruption of the functional activity of KLF6 gene products may be one of the early events in tumor genesis of the colon. The main objective of the present study was to detect mutational changes of KLF6 tumor suppressor gene and to study the loss of heterozygosity (LOH) markers at chromosome 10p15 (KLF6 locus) in colorectal lesions and colorectal cancer in Egyptian patients. The patients included in this study were 83 presented with different indications for colonoscopic examination. Selecting patients with colorectal pre-cancerous lesions or colorectal cancer was done according to the results of tissue biopsy from lesion and adjacent normal. The patients were classified into three main groups; (G I) Cancerous group, (G II) polyps group including patients with adenomatous polyps (AP), familial adenomatous polyps (FAP) and hyperplastic polyps (HP) and (G III) Inflammatory Bowel Diseases (IBD) including patients with ulcerative colitis (UC) and Crohn's disease (CD

  3. Erg gene: a human gene related to the ets oncogene

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, E.S.P.; Rao, V.N.; Papas, T.S.

    1987-09-01

    The authors have isolated a cDNA clone representing the complete coding sequence of a human gene named erg, related to the ets oncogene. Nucleotide sequence analysis of this cDNA (4.6 kilobases long) revealed that this gene encodes a 363-residue protein whose predicted amino acid sequence showed a homology of approx. = 40% and 70% to two domains corresponding to the 5' and 3' regions of v-ets oncogene, respectively. A 3.2- to 3.6-kilobase and approx. = 5-kilobase transcript of the erg gene, which differ in size from those of the previously described Hu-ets 1 and Hu-ets 2 genes, were observed in different cells. These results suggest that the erg gene is a member of the ets oncogen family.

  4. Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

    OpenAIRE

    Wang, Ming-Hsi; FIOCCHI, CLAUDIO; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

    2013-01-01

    Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust...

  5. Evidence Based Selection of Housekeeping Genes

    OpenAIRE

    de Jonge, Hendrik J.M.; Fehrmann, Rudolf S. N.; Eveline S. J. M. de Bont; Hofstra, Robert M. W.; Gerbens, Frans; Kamps, Willem A.; Vries, Elisabeth G. E.; van der Zee, Ate G.J.; te Meerman, Gerard J.; ter Elst, Arja

    2007-01-01

    For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e.g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental conditions and therefore their use for normalization is limited. We performed a meta-analysis of 13,629 human gene array samples in order to identify the most stable expressed genes. Here we show n...

  6. Advancement and prospects of tumor gene therapy

    OpenAIRE

    Zhang, Chao; Wang, Qing-Tao; Liu, He; Zhang, Zhen-Zhu; Huang, Wen-Lin

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA inter...

  7. P15: The expression of Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders

    Science.gov (United States)

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (PTc17 cells in MG/AD group was significantly higher than that in Tm, was statistically significant (PTc17 cells have risen trend in Tm groups and MG/AD group. Conclusions (I) CD8+ cells, CD4+/CD8+ T ratio, immunoglobulin, CRP and complement C3 levels can be used as indicators of evaluation of the role of the immune status of patients with thymoma; (II) RORγt mRNA is the key factors of Th17/Tcl7 cells differentiation, it may play an important role in thymoma accompany with autoimmune diseases or autoimmune disorders; (III) all these authenticate that Th17/Tcl7 cells are involved in the antitumor immunity and autoimmune disorders, which may offer evidence to a probability of immunotherapy.

  8. Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung.

    Directory of Open Access Journals (Sweden)

    Steven K Huang

    Full Text Available Excessive fibroproliferation is a central hallmark of idiopathic pulmonary fibrosis (IPF, a chronic, progressive disorder that results in impaired gas exchange and respiratory failure. Fibroblasts are the key effector cells in IPF, and aberrant expression of multiple genes contributes to their excessive fibroproliferative phenotype. DNA methylation changes are critical to the development of many diseases, but the DNA methylome of IPF fibroblasts has never been characterized. Here, we utilized the HumanMethylation 27 array, which assays the DNA methylation level of 27,568 CpG sites across the genome, to compare the DNA methylation patterns of IPF fibroblasts (n = 6 with those of nonfibrotic patient controls (n = 3 and commercially available normal lung fibroblast cell lines (n = 3. We found that multiple CpG sites across the genome are differentially methylated (as defined by P value less than 0.05 and fold change greater than 2 in IPF fibroblasts compared to fibroblasts from nonfibrotic controls. These methylation differences occurred both in genes recognized to be important in fibroproliferation and extracellular matrix generation, as well as in genes not previously recognized to participate in those processes (including organ morphogenesis and potassium ion channels. We used bisulfite sequencing to independently verify DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT; these methylation changes corresponded with differences in gene expression at the mRNA and protein level. These differences in DNA methylation were stable throughout multiple cell passages. DNA methylation differences may thus help to explain a proportion of the differences in gene expression previously observed in studies of IPF fibroblasts. Moreover, significant variability in DNA methylation was observed among individual IPF cell lines, suggesting that differences in DNA methylation may contribute to fibroblast heterogeneity among patients with IPF

  9. Candidate gene prioritization with Endeavour.

    Science.gov (United States)

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/. PMID:27131783

  10. Candidate genes for behavioural ecology

    NARCIS (Netherlands)

    Fitzpatrick, M.J.; Ben-Sahar, Y.; Smid, H.M.; Vet, L.E.M.; Robinson, G.E.; Sokolowski, M.B.

    2005-01-01

    In spite of millions of years of evolutionary divergence, the conservation of gene function is common across distant lineages. As such, genes that are known to influence behaviour in one organism are likely to influence similar behaviours in other organisms. Recent studies of the evolution of behavi

  11. Gene polymorphisms in chronic periodontitis

    NARCIS (Netherlands)

    M.L. Laine; B.G. Loos; W. Crielaard

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polym

  12. FunGeneClusterS

    DEFF Research Database (Denmark)

    Vesth, Tammi Camilla; Brandl, Julian; Andersen, Mikael Rørdam

    2016-01-01

    Secondary metabolites of fungi are receiving an increasing amount of interest due to their prolific bioactivities and the fact that fungal biosynthesis of secondary metabolites often occurs from co-regulated and co-located gene clusters. This makes the gene clusters attractive for synthetic biology...

  13. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  14. Multifunctional nanorods for gene delivery

    Science.gov (United States)

    Salem, Aliasger K.; Searson, Peter C.; Leong, Kam W.

    2003-10-01

    The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

  15. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...

  16. Phytochrome-regulated Gene Expression

    Institute of Scientific and Technical Information of China (English)

    Peter H. Quail

    2007-01-01

    Identification of all genes involved in the phytochrome (phy)-mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-regulated genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an initial subset of these genes. The data: (a) reveal considerable complexity in the channeling of the light signals through the different phy-family members (phyA to phyE) to responsive genes; (b) identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, and, therefore, as potentially important regulators in the transcriptional-network hierarchy; and (c) identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetiolation.

  17. Nonviral Vectors for Gene Delivery

    Science.gov (United States)

    Baoum, Abdulgader Ahmed

    2011-12-01

    The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was

  18. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder;

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...... known genes and 157 ESTs were found to be highly relevant for CRC. The alteration of known genes was confirmed in >70% of the cases by array analysis of 25 single samples. Two-way hierarchical average linkage cluster analysis clustered normal tissue together with Dukes' A, clustered Dukes' B with Dukes...

  19. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa....... Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until...... formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer...

  20. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  1. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... to describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can...... genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry based proteome...

  2. GeneMANIA Prediction Server 2013 Update

    OpenAIRE

    Zuberi, Khalid; Franz, Max; Rodriguez, Harold; Montojo, Jason; Lopes, Christian Tannus; Bader, Gary D.; Morris, Quaid

    2013-01-01

    GeneMANIA (http://www.genemania.org) is a flexible user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. GeneMANIA can also be used in a function predict...

  3. Gene expression profiling: can we identify the right target genes?

    Directory of Open Access Journals (Sweden)

    J. E. Loyd

    2008-12-01

    Full Text Available Gene expression profiling allows the simultaneous monitoring of the transcriptional behaviour of thousands of genes, which may potentially be involved in disease development. Several studies have been performed in idiopathic pulmonary fibrosis (IPF, which aim to define genetic links to the disease in an attempt to improve the current understanding of the underlying pathogenesis of the disease and target pathways for intervention. Expression profiling has shown a clear difference in gene expression between IPF and normal lung tissue, and has identified a wide range of candidate genes, including those known to encode for proteins involved in extracellular matrix formation and degradation, growth factors and chemokines. Recently, familial pulmonary fibrosis cohorts have been examined in an attempt to detect specific genetic mutations associated with IPF. To date, these studies have identified families in which IPF is associated with mutations in the gene encoding surfactant protein C, or with mutations in genes encoding components of telomerase. Although rare and clearly not responsible for the disease in all individuals, the nature of these mutations highlight the importance of the alveolar epithelium in disease pathogenesis and demonstrate the potential for gene expression profiling in helping to advance the current understanding of idiopathic pulmonary fibrosis.

  4. Genes and gene networks implicated in aggression related behaviour.

    Science.gov (United States)

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

  5. Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse,fish,fly,and worm

    Institute of Scientific and Technical Information of China (English)

    Chun-Xia Wang; Andreas Teufel; Uta Cheruti; Joachim Gr(o)tzinger; Peter R Galle; Ansgar W Lohse; Johannes Herkel

    2006-01-01

    AIM: To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species.METHODS: By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse,zebrafish, fly, and worm.RESULTS: The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis (AIH) patients.CONCLUSION: The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evoluti n, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.

  6. Whole body analysis of the knockout gene mouse model for cystic fibrosis using thermal and fast neutron activation analysis

    International Nuclear Information System (INIS)

    A genetically engineered 'knockout gene' mouse model for human cystic fibrosis (CF) has been utilized to study bone mineralization. In CF, the so-called cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride ion channel, is either absent or defective. To produce the animal model the murine CFTR gene has been inactivated producing CF symptoms in the homozygotic progeny. CF results in abnormal intestinal absorption of minerals and nutrients which presumably results in substandard bone mineralization. The objective of this study was to determine the feasibility of using whole-body thermal and fast neutron activation analysis to determine mineral and trace-element differences between homozygote controls (+/+) and CF (-/-), murine siblings. Gender-matched juvenile +/+ and -/- litter mates were lyophilized and placed in a BN capsule to reduce thermal-neutron activation and irradiated for 10 seconds at φfast ∼ 1 x 1013 n x cm-2 x s-1 using the MURR pneumatic-tube facility. Phosphorus was measured via the 31P15(n,α)28Al13 reaction. After several days decay, the whole-body specimens were re-irradiated in the same facility, but without thermal-neutron shielding, for 5 seconds and the gamma-ray spectrum was recorded at two different decay periods allowing measurement of 77mSe, 24Na, 27mg, 38Cl, 42k, 49Ca, 56Mn, 66Cu and 80Br from the corresponding radiative-capture reactions. (author)

  7. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  8. Genes, Economics, and Happiness.

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Christakis, Nicholas A; Fowler, James H; Frey, Bruno S

    2012-11-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being.

  9. Genes and equality.

    Science.gov (United States)

    Farrelly, C

    2004-12-01

    The way people think about equality as a value will influence how they think genetic interventions should be regulated. In this paper the author uses the taxonomy of equality put forth by Derek Parfit and applies this to the issue of genetic interventions. It is argued that telic egalitarianism is untenable and that deontic egalitarianism collapses into prioritarianism. The priority view maintains that it is morally more important to benefit the people who are worse off. Once this precision has been given to the concerns egalitarians have, a number of diverse issues must be considered before determining what the just regulation of genetic interventions would be. Consideration must be given to the current situation of the least advantaged, the fiscal realities behind genetic interventions, the budget constraints on other social programmes egalitarians believe should receive scarce public funds, and the interconnected nature of genetic information. These considerations might lead egalitarians to abandon what they take to be the obvious policy recommendations for them to endorse regarding the regulation of gene therapies and enhancements. PMID:15574450

  10. Genes, Economics, and Happiness.

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Christakis, Nicholas A; Fowler, James H; Frey, Bruno S

    2012-11-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601

  11. Gene Electrotransfer: A Mechanistic Perspective.

    Science.gov (United States)

    Rosazza, Christelle; Meglic, Sasa Haberl; Zumbusch, Andreas; Rols, Marie-Pierre; Miklavcic, Damijan

    2016-01-01

    Gene electrotransfer is a powerful method of DNA delivery offering several medical applications, among the most promising of which are DNA vaccination and gene therapy for cancer treatment. Electroporation entails the application of electric fields to cells which then experience a local and transient change of membrane permeability. Although gene electrotransfer has been extensively studied in in vitro and in vivo environments, the mechanisms by which DNA enters and navigates through cells are not fully understood. Here we present a comprehensive review of the body of knowledge concerning gene electrotransfer that has been accumulated over the last three decades. For that purpose, after briefly reviewing the medical applications that gene electrotransfer can provide, we outline membrane electropermeabilization, a key process for the delivery of DNA and smaller molecules. Since gene electrotransfer is a multipart process, we proceed our review in describing step by step our current understanding, with particular emphasis on DNA internalization and intracellular trafficking. Finally, we turn our attention to in vivo testing and methodology for gene electrotransfer. PMID:27029943

  12. Genes: an Open Access Journal

    Directory of Open Access Journals (Sweden)

    J. Peter W. Young

    2009-11-01

    Full Text Available Genes have been in the scientific vocabulary for a hundred years. The term "gene" was proposed by the Danish plant scientist Wilhelm Johannsen in the first decade of the 20th century. For Johannsen, the gene remained an abstract concept, "free of any hypothesis" [1], but others were already pointing to chromosomes as the likely location of genes. The science of genetics was born at that time, and genes were rapidly connected with mutations, with patterns of inheritance, with development, with quantitative traits, with evolution and with biochemical pathways. All this was achieved without knowledge of the physical nature of genes, but this changed in mid-century with the discoveries of molecular biology. DNA was revealed as the genetic material, and the mechanisms were elucidated by which the information was encoded, and propagated, and linked to the phenotype. However, the concept of a "gene" did not become clearer. Quite the reverse, as the units of mutation, of recombination, of inheritance, of expression, of regulation, etc. did not necessarily coincide. [...

  13. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    Science.gov (United States)

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  14. GeneNet: a database on structure and functional organisation of gene networks

    OpenAIRE

    Ananko, E A; Podkolodny, N. L.; Stepanenko, I. L.; Ignatieva, E. V.; Podkolodnaya, O. A.; Kolchanov, N. A.

    2002-01-01

    The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 pr...

  15. Genes Might Explain Hispanics' Added Longevity

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160528.html Genes Might Explain Hispanics' Added Longevity Differences in 'genetic ... Services, or federal policy. More Health News on: Genes and Gene Therapy Hispanic American Health Recent Health ...

  16. Personalized Medicine: Matching Treatments to Your Genes

    Science.gov (United States)

    ... disclaimer . Subscribe Personalized Medicine Matching Treatments to Your Genes You’re one of a kind. It’s not ... personalized medicine begins with the unique set of genes you inherited from your parents. Genes are stretches ...

  17. Basics on Genes and Genetic Disorders

    Science.gov (United States)

    ... Help a Friend Who Cuts? The Basics on Genes and Genetic Disorders KidsHealth > For Teens > The Basics ... such as treating health problems. What Is a Gene? To understand how genes work, let's review some ...

  18. Gene Therapy for Diseases and Genetic Disorders

    Science.gov (United States)

    ... Mentor Submit Your Press Release Donate Home ASGCT Gene Therapy for Diseases Gene Therapy has made important ... Among the most notable advancements are the following: Gene Therapy for Genetic Disorders Severe Combined Immune Deficiency ( ...

  19. The Ensembl gene annotation system.

    Science.gov (United States)

    Aken, Bronwen L; Ayling, Sarah; Barrell, Daniel; Clarke, Laura; Curwen, Valery; Fairley, Susan; Fernandez Banet, Julio; Billis, Konstantinos; García Girón, Carlos; Hourlier, Thibaut; Howe, Kevin; Kähäri, Andreas; Kokocinski, Felix; Martin, Fergal J; Murphy, Daniel N; Nag, Rishi; Ruffier, Magali; Schuster, Michael; Tang, Y Amy; Vogel, Jan-Hinnerk; White, Simon; Zadissa, Amonida; Flicek, Paul; Searle, Stephen M J

    2016-01-01

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail.Database URL: http://www.ensembl.org/index.html. PMID:27337980

  20. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin;

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  1. Panspermia and horizontal gene transfer

    Science.gov (United States)

    Klyce, Brig

    2009-08-01

    Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

  2. [Pathogenicity and pneumococcal capsular genes].

    Science.gov (United States)

    García, E; García, P; López, R

    1994-01-01

    Pneumococci remain to be one of the most prominent human pathogens. Increasing efforts are being dedicated to the development of improved vaccines with wider specificity. Since a clear understanding of the genetics of capsular types in Streptococcus pneumoniae is missing, our efforts are oriented to characterize, at the molecular level, the genes involved in capsular polysaccharide biosynthesis. We have cloned and sequenced a chromosomal DNA fragment of a clinical isolate of type 3 pneumococcus and showed that it contains a type 3 specific gene as well as genes common to other serotypes.

  3. Parsimonious selection of useful genes in microarray gene expression data

    OpenAIRE

    González Navarro, Félix Fernando; Belanche Muñoz, Luis Antonio

    2011-01-01

    Machine Learning methods have of late made significant efforts to solving multidisciplinary problems in the field of cancer classification in microarray gene expression data. These tasks are characterized by a large number of features and a few observations, making the modeling a non-trivial undertaking. In this work we apply entropic filter methods for gene selection, in combination with several off-the-shelf classifiers. The introduction of bootstrap resampling techniques permits the achiev...

  4. Integrating Gene Ontology and Blast to predict gene functions

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-gang; MO Zhi-hong

    2007-01-01

    A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by wu-formatdb program. The GoBlast system includes three Bioperl modules in Perl: a data input module, a data process module and a data output module. A GoBlast query starts with an amino acid or nucleotide sequence. It ends with an output in an html page, presenting high scoring gene products which are of a high homology to the queried sequence and listing associated GO terms beside respective gene poducts. A simple click on a GO term leads to the detailed explanation of the specific gene function. This avails gene function prediction by Blast. GoBlast can be a very useful tool for functional genome research and is available for free at http://bioq.org/goblast.

  5. Viral vectors for vascular gene therapy

    OpenAIRE

    Fischer, Lukas; Preis, Meir; Weisz, Anat; Koren, Belly; Lewis, Basil S; Flugelman, Moshe Y

    2002-01-01

    Vascular gene therapy is the focus of multiple experimental and clinical research efforts. While several genes with therapeutic potential have been identified, the best method of gene delivery is unknown. Viral vectors have the capacity to transfer genes at high efficiency rates. Several viral-based vectors have been used in experimental vascular gene therapy for in vivo and ex vivo gene transfer. Adenoviral-based vectors are being used for the induction of angiogenesis in phase 1 and 2 clini...

  6. Evolution of the nuclear receptor gene superfamily.

    OpenAIRE

    Laudet, V; Hänni, C; Coll, J.; F. Catzeflis; Stéhelin, D

    1992-01-01

    Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplica...

  7. Evolution of alternative splicing after gene duplication

    OpenAIRE

    Su, Zhixi; Wang, Jianmin; Yu, Jun; Huang, Xiaoqiu; Gu, Xun

    2006-01-01

    Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice (AS) forms than single-copy genes, and that a negative correlation exists between the mean number of AS forms and the gene family size. Interestingly, we found that the loss of ...

  8. Activation of p21CIP1/WAF1 gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4α

    International Nuclear Information System (INIS)

    The F9 murine embryonal carcinoma cell line provides an attractive system for studying epithelial differentiation and antiproliferative processes. We have recently established F9 cells expressing doxycycline-inducible hepatocyte nuclear factor (HNF)-4α and shown that HNF-4α triggers the gene expression of tight-junction molecules, occludin, claudin-6, and claudin-7, as well as formation of functional tight junctions and polarized epithelial morphology (Exp. Cell Res. 286, [2003] 288). Since these events were very similar to those induced by retinoids, we investigated whether HNF-4α, like retinoid receptors, was involved in the control of cell proliferation. We herein show that HNF-4α up-regulates expression of the p21 gene, but not the p15, p16, p18, p19, or p27 gene, in a p53-independent manner, and inhibits cell growth in F9 cells. Similar results were observed in rat lung endothelial cells, in which expression of HNF-4α is conditionally induced by doxycycline. Furthermore, we demonstrate, by reporter assay, that HNF-4α significantly elevates the transcriptional activity of the p21 promoter. Since, HNF-4α is expressed not only in the liver but also in organs containing epithelial cells, such as kidney, intestine, pancreas, and stomach, it might also play critical roles in the regulation of epithelial morphogenesis and proliferation in these organs

  9. MADS-box gene evolution - structure and transcription patterns

    DEFF Research Database (Denmark)

    Johansen, Bo; Pedersen, Louise Buchholt; Skipper, Martin;

    2002-01-01

    Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs......Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs...

  10. Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.

    Science.gov (United States)

    Debray, François-Guillaume; Stümpfig, Claudia; Vanlander, Arnaud V; Dideberg, Vinciane; Josse, Claire; Caberg, Jean-Hubert; Boemer, François; Bours, Vincent; Stevens, René; Seneca, Sara; Smet, Joél; Lill, Roland; van Coster, Rudy

    2015-11-01

    Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect. Respiratory chain studies in skeletal muscle isolated from the proband revealed a combined deficiency of complexes I and II. In addition, western blotting indicated lack of protein lipoylation. The combination of these findings was suggestive for a defect in the iron-sulfur (Fe/S) protein assembly pathway. SNP array identified loss of heterozygosity in large chromosomal regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes, in 2p15-p11.2 and 1q31.1-q42.13, respectively. A homozygous c.436C > T (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing. Complementation studies in a HeLa cell line depleted for IBA57 showed that the mutant protein with the semi-conservative amino acid exchange was unable to restore the biochemical phenotype indicating a loss-of-function mutation of IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause autosomal recessive neurodegeneration associated with progressive leukodystrophy and fatal outcome at young age. In the affected patient, the biochemical phenotype was characterized by a defect in the respiratory chain complexes I and II and a decrease in mitochondrial protein lipoylation, both resulting from impaired assembly of Fe/S clusters.

  11. Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II.

    Science.gov (United States)

    Hühn, R; Stoermer, H; Klingele, B; Bausch, E; Fois, A; Farnetani, M; Di Rocco, M; Boué, J; Kirk, J M; Coleman, R; Scherer, G

    1998-03-01

    Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disorder of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. The disease results from deficiency in hepatic tyrosine aminotransferase (TAT). We have previously described one deletion and six different point mutations in four RHS patients. We have now analyzed the TAT genes in a further seven unrelated RHS families from Italy, France, the United Kingdom, and the United States. We have established PCR conditions for the amplification of all twelve TAT exons and have screened the products for mutations by direct sequence analysis or by first performing single-strand conformation polymorphism analysis. We have thus identified the presumably pathological mutations in eight RHS alleles, including two nonsense mutations (R57X, E411X) and four amino acid substitutions (R119W, L201R, R433Q, R433W). Only the R57X mutation, which was found in one Scottish and two Italian families, has been previously reported in another Italian family. Haplotype analysis indicates that this mutation, which involves a CpG dinucleotide hot spot, has a common origin in the three Italian families but arose independently in the Scottish family. Two polymorphisms have also been detected, viz., a protein polymorphism, P15S, and a silent substitution S103S (TCG-->TCA). Expression of R433Q and R433W demonstrate reduced activity of the mutant proteins. In all, twelve different TAT gene mutations have now been identified in tyrosinemia type II.

  12. Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.

    Science.gov (United States)

    Debray, François-Guillaume; Stümpfig, Claudia; Vanlander, Arnaud V; Dideberg, Vinciane; Josse, Claire; Caberg, Jean-Hubert; Boemer, François; Bours, Vincent; Stevens, René; Seneca, Sara; Smet, Joél; Lill, Roland; van Coster, Rudy

    2015-11-01

    Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect. Respiratory chain studies in skeletal muscle isolated from the proband revealed a combined deficiency of complexes I and II. In addition, western blotting indicated lack of protein lipoylation. The combination of these findings was suggestive for a defect in the iron-sulfur (Fe/S) protein assembly pathway. SNP array identified loss of heterozygosity in large chromosomal regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes, in 2p15-p11.2 and 1q31.1-q42.13, respectively. A homozygous c.436C > T (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing. Complementation studies in a HeLa cell line depleted for IBA57 showed that the mutant protein with the semi-conservative amino acid exchange was unable to restore the biochemical phenotype indicating a loss-of-function mutation of IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause autosomal recessive neurodegeneration associated with progressive leukodystrophy and fatal outcome at young age. In the affected patient, the biochemical phenotype was characterized by a defect in the respiratory chain complexes I and II and a decrease in mitochondrial protein lipoylation, both resulting from impaired assembly of Fe/S clusters. PMID:25971455

  13. Systematic association mapping identifies NELL1 as a novel IBD disease gene.

    Directory of Open Access Journals (Sweden)

    Andre Franke

    Full Text Available Crohn disease (CD, a sub-entity of inflammatory bowel disease (IBD, is a complex polygenic disorder. Although recent studies have successfully identified CD-associated genetic variants, these susceptibility loci explain only a fraction of the heritability of the disease. Here, we report on a multi-stage genome-wide scan of 393 German CD cases and 399 controls. Among the 116,161 single-nucleotide polymorphisms tested, an association with the known CD susceptibility gene NOD2, the 5q31 haplotype, and the recently reported CD locus at 5p13.1 was confirmed. In addition, SNP rs1793004 in the gene encoding nel-like 1 precursor (NELL1, chromosome 11p15.1 showed a consistent disease-association in independent German population- and family-based samples (942 cases, 1082 controls, 375 trios. Subsequent fine mapping and replication in an independent sample of 454 French/Canadian CD trios supported the authenticity of the NELL1 association. Further confirmation in a large German ulcerative colitis (UC sample indicated that NELL1 is a ubiquitous IBD susceptibility locus (combined p<10(-6; OR = 1.66, 95% CI: 1.30-2.11. The novel 5p13.1 locus was also replicated in the French/Canadian sample and in an independent UK CD patient panel (453 cases, 521 controls, combined p<10(-6 for SNP rs1992660. Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream, GRM8 (downstream, OR5V1 (downstream, PPP3R2 (downstream, NM_152575 (upstream and HNF4G (intron.

  14. The evolution of resistance gene in plants

    Institute of Scientific and Technical Information of China (English)

    BEN Haiyan; LIU Xuemin; LI Lijun; LIU Li

    2007-01-01

    Resistance genes enable plants to fight against plant pathogens. Plant resistance genes (R gene) are organized complexly in genome. Some resistance gene sequence data enable an insight into R gene structure and gene evolution. Some sites like Leucine-Rich Repeat (LRR) are of specific interest since homologous recombination can happen. Crossing over, transposon insertion and excision and mutation can produce new specificity. Three models explaining R gene evolution were discussed. More information needed for dissection of R gene evolution though some step can be inferred from genetic and sequence analysis.

  15. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer

    2012-01-01

    Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

  16. Gene discovery in Triatoma infestans

    Directory of Open Access Journals (Sweden)

    de Burgos Nelia

    2011-03-01

    Full Text Available Abstract Background Triatoma infestans is the most relevant vector of Chagas disease in the southern cone of South America. Since its genome has not yet been studied, sequencing of Expressed Sequence Tags (ESTs is one of the most powerful tools for efficiently identifying large numbers of expressed genes in this insect vector. Results In this work, we generated 826 ESTs, resulting in an increase of 47% in the number of ESTs available for T. infestans. These ESTs were assembled in 471 unique sequences, 151 of which represent 136 new genes for the Reduviidae family. Conclusions Among the putative new genes for the Reduviidae family, we identified and described an interesting subset of genes involved in development and reproduction, which constitute potential targets for insecticide development.

  17. Gene therapy in lung transplantation.

    Science.gov (United States)

    Sato, Masaaki; Keshavjee, Shaf

    2006-08-01

    Lung transplantation is effective life-saving therapy for the treatment of a variety of end-stage lung diseases. However, the application of lung transplantation is hindered by multiple factors such as the shortage of organ donors, early graft failure and chronic graft dysfunction. These problems are related to various lung injuries before and after transplantation including donor brain-death-related lung injury, ischemia, reperfusion and immune-mediated injuries. Gene transfection presents a potential molecular therapeutic solution to modify the transplanted organ such that it is better able to deal with these obstacles. In fact, in many ways lung transplantation is an ideal situation for gene therapy in that: 1) the targeted injuries are predictable (e.g. IR injury), 2) only transient gene expression is needed in many instances, 3) the immunosuppressive regimen necessary to prevent rejection of the transplanted organ attenuates vector-induced inflammation and the immune response to the vectors or the transgene products, and thus effectively augments and prolongs gene expression; 4) the anatomical structure of the lung enables trans-airway access and local gene delivery - as well as re-transfection. A number of issues need to be considered to develop a strategy of gene delivery in lung transplantation: administration route (intra-airway, trans-vascular, intravenous, intramuscular), timing (donor in-vivo, ex-vivo organ transfection or recipient), vector selection and gene selection. Based on our work and the work of others, over the last decade, we present the state of art of in gene therapy in lung transplantation and exciting future directions in the field. PMID:16918334

  18. Shuffling Yeast Gene Expression Data

    OpenAIRE

    Bilke, Sven

    2000-01-01

    A new method to sort gene expression patterns into functional groups is presented. The method is based on a sorting algorithm using a non-local similarity score, which takes all other patterns in the dataset into account. The method is therefore very robust with respect to noise. Using the expression data for yeast, we extract information about functional groups. Without prior knowledge of parameters the cell cycle regulated genes in yeast can be identified. Furthermore a second, independent ...

  19. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  20. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  1. Gemini surfactants as gene carriers

    Directory of Open Access Journals (Sweden)

    Teresa Piskorska

    2010-03-01

    Full Text Available Gemini surfactants are a new class of amphiphilic compounds built from two classic surfactant moieties bound together by a special spacer group. These compounds appear to be excellent for creating complexes with DNA and are effective in mediating transfection. Thanks to their construction, DNA carrier molecules built from gemini surfactants are able to deliver genes to cells of almost any DNA molecule size, unattainable when using viral gene delivery systems. Moreover, they are much safer for living organisms.

  2. Gene therapy in clinical medicine

    OpenAIRE

    Selkirk, S

    2004-01-01

    Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Over the next decade, the relevance of gene therapy to medical practices will increase and it will become important for physicians to understand the basic principles and st...

  3. Vascular gene expression: a hypothesis

    OpenAIRE

    Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

    2013-01-01

    The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular ti...

  4. Rice's Salt Tolerance Gene Cloned

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ In cooperation with US colleagues, CAS researchers have made significant progress in their studies into functional genes for key agronomic traits by cloning SKC1, a salt-tolerant functional gene of rice and making clear its biological functions and mechanisms. This pioneering work,which was reported in the Oct. issue of Nature Genetics (37:1141-1146), is believed to hold promise to increase the output of the crop plant in this country.

  5. Gene Polymorphisms in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Marja L. Laine

    2010-01-01

    Full Text Available We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP.

  6. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  7. Immunoglobulin genes of the turtles.

    Science.gov (United States)

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  8. Origin and evolution of new genes

    Institute of Scientific and Technical Information of China (English)

    LI Xin; YANG Shuang; PENG Lixin; CHEN Hong; WANG Wen

    2004-01-01

    Organisms have variable genome sizes andcontain different numbers of genes. This difference demonstrates that new gene origination is a fundamental process in evolutionary biology. Though the study of the origination of new genes dated back more than half a century ago, it is not until the 1990s when the first young genejingwei was found that empirical investigation of the molecular mechanisms of origination of new genes became possible. In the recent years,several young genes were identified and the studies on these genes have greatly enriched the knowledge of this field. Yet more details in a general picture of new genes origination are to be clarified. We have developed a systematic approach to searching for young genes at the genomic level, in the hope to summarize a general pattern of the origination and evolution of new genes, such as the rate of new gene appearance, impact of new genes on their host genomes, etc.

  9. Noninvasive tracking of gene transcript and neuroprotection after gene therapy.

    Science.gov (United States)

    Ren, J; Chen, Y I; Liu, C H; Chen, P-C; Prentice, H; Wu, J-Y; Liu, P K

    2016-01-01

    Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine. PMID:26207935

  10. Sequencing and Gene Expression Analysis of Leishmania tropica LACK Gene.

    Directory of Open Access Journals (Sweden)

    Nour Hammoudeh

    2014-12-01

    Full Text Available Leishmania Homologue of receptors for Activated C Kinase (LACK antigen is a 36-kDa protein, which provokes a very early immune response against Leishmania infection. There are several reports on the expression of LACK through different life-cycle stages of genus Leishmania, but only a few of them have focused on L.tropica.The present study provides details of the cloning, DNA sequencing and gene expression of LACK in this parasite species. First, several local isolates of Leishmania parasites were typed in our laboratory using PCR technique to verify of Leishmania parasite species. After that, LACK gene was amplified and cloned into a vector for sequencing. Finally, the expression of this molecule in logarithmic and stationary growth phase promastigotes, as well as in amastigotes, was evaluated by Reverse Transcription-PCR (RT-PCR technique.The typing result confirmed that all our local isolates belong to L.tropica. LACK gene sequence was determined and high similarity was observed with the sequences of other Leishmania species. Furthermore, the expression of LACK gene in both promastigotes and amastigotes forms was confirmed.Overall, the data set the stage for future studies of the properties and immune role of LACK gene products.

  11. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar

    2013-11-01

    Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  12. Characterizing gene-gene interactions in a statistical epistasis network of twelve candidate genes for obesity

    OpenAIRE

    Rishika; Hu, Ting; Moore, Jason H.; Gilbert-Diamond, Diane

    2015-01-01

    Background Recent findings have reemphasized the importance of epistasis, or gene-gene interactions, as a contributing factor to the unexplained heritability of obesity. Network-based methods such as statistical epistasis networks (SEN), present an intuitive framework to address the computational challenge of studying pairwise interactions between thousands of genetic variants. In this study, we aimed to analyze pairwise interactions that are associated with Body Mass Index (BMI) between SNPs...

  13. Methylation of multiple genes in hepatitis C virus associated hepatocellular carcinoma.

    Science.gov (United States)

    Zekri, Abdel-Rahman N; Bahnasy, Abeer A; Shoeab, Fatma Elzahraa M; Mohamed, Waleed S; El-Dahshan, Dina H; Ali, Fahmey T; Sabry, Gilane M; Dasgupta, Nairajana; Daoud, Sayed S

    2014-01-01

    We studied promoter methylation (PM) of 11 genes in Peripheral Blood Lymphocytes (PBLs) and tissues of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) and chronic hepatitis (CH) Egyptian patients. The present study included 31 HCC with their ANT, 38 CH and 13 normal hepatic tissue (NHT) samples. In all groups, PM of APC, FHIT, p15, p73, p14, p16, DAPK1, CDH1, RARβ, RASSF1A, O(6)MGMT was assessed by methylation-specific PCR (MSP). APC and O6-MGMT protein expression was assessed by immunohistochemistry (IHC) in the studied HCC and CH (20 samples each) as well as in a different HCC and CH set for confirmation of MSP results. PM was associated with progression from CH to HCC. Most genes showed high methylation frequency (MF) and the methylation index (MI) increased with disease progression. MF of p14, p73, RASSF1A, CDH1 and O(6)MGMT was significantly higher in HCC and their ANT. MF of APC was higher in CH. We reported high concordance between MF in HCC and their ANT, MF in PBL and CH tissues as well as between PM and protein expression of APC and O(6)MGMT. A panel of 4 genes (APC, p73, p14, O(6)MGMT) classifies the cases independently into HCC and CH with high accuracy (89.9%), sensitivity (83.9%) and specificity (94.7%). HCV infection may contribute to hepatocarcinogenesis through enhancing PM of multiple genes. PM of APC occurs early in the cascade while PM of p14, p73, RASSF1A, RARB, CDH1 and O(6)MGMT are late changes. A panel of APC, p73, p14, O6-MGMT could be used in monitoring CH patients for early detection of HCC. Also, we found that, the methylation status is not significantly affected by whether the tissue was from the liver or PBL, indicating the possibility of use PBL as indicator to genetic profile instead of liver tissue regardless the stage of disease. PMID:25685469

  14. Methylation of multiple genes in hepatitis C virus associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Abdel-Rahman N. Zekri

    2014-01-01

    Full Text Available We studied promoter methylation (PM of 11 genes in Peripheral Blood Lymphocytes (PBLs and tissues of hepatitis C virus (HCV associated hepatocellular carcinoma (HCC and chronic hepatitis (CH Egyptian patients. The present study included 31 HCC with their ANT, 38 CH and 13 normal hepatic tissue (NHT samples. In all groups, PM of APC, FHIT, p15, p73, p14, p16, DAPK1, CDH1, RARβ, RASSF1A, O6MGMT was assessed by methylation-specific PCR (MSP. APC and O6-MGMT protein expression was assessed by immunohistochemistry (IHC in the studied HCC and CH (20 samples each as well as in a different HCC and CH set for confirmation of MSP results. PM was associated with progression from CH to HCC. Most genes showed high methylation frequency (MF and the methylation index (MI increased with disease progression. MF of p14, p73, RASSF1A, CDH1 and O6MGMT was significantly higher in HCC and their ANT. MF of APC was higher in CH. We reported high concordance between MF in HCC and their ANT, MF in PBL and CH tissues as well as between PM and protein expression of APC and O6MGMT. A panel of 4 genes (APC, p73, p14, O6MGMT classifies the cases independently into HCC and CH with high accuracy (89.9%, sensitivity (83.9% and specificity (94.7%. HCV infection may contribute to hepatocarcinogenesis through enhancing PM of multiple genes. PM of APC occurs early in the cascade while PM of p14, p73, RASSF1A, RARB, CDH1 and O6MGMT are late changes. A panel of APC, p73, p14, O6-MGMT could be used in monitoring CH patients for early detection of HCC. Also, we found that, the methylation status is not significantly affected by whether the tissue was from the liver or PBL, indicating the possibility of use PBL as indicator to genetic profile instead of liver tissue regardless the stage of disease.

  15. Seven Novel and Stable Translocations Associated with Oncogenic Gene Expression in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ichiro Okamoto

    2005-04-01

    Full Text Available Cytogenetics has not only precipitated the discovery of several oncogenes, but has also led to the molecular classification of numerous malignancies. The correct identification of aberrations in many tumors has, however, been hindered by extensive tumor complexity and the limitations of molecular cytogenetic techniques. In this study, we have investigated five malignant melanoma (MM cell lines from at least three different passages using high-resolution R-banding and the recently developed methods of comparative genomic hybridization and multicolor or multiplex fluorescence in situ hybridization. We subsequently detected nine consistent translocations, seven of which were novel: dic(1;11(p10;q14, der(9t(3;9(p12;p11, der(4t(9;4;7(q33::p15-q23::q21, der(14t(5;14 (q12;q32, der(9t(9;22(p21;q11, der(19t(19;20(p13.3;p11, der(10t(2;12;7;10(q31::p12→pter::q11.2→q31::q21,der(19t(10;19(q23;q13, and der(20t(Y;20(q11.23;q13.3. Furthermore, using the human HG-U133A Gene-Chip, positive expression levels of oncogenes or tumor-related genes located at the regions of chromosomal breakpoints were identified, including AKT1, BMI1, CDK6, CTNNB1, E2F1, GPNMB, GPRK7, KBRAS2, LDB2, LIMK1, MAPK1, MEL, MP1, MUC18, NRCAM, PBX3, RAB22A, RAB38, SNK, and STK4, indicating an association between chromosomal breakpoints and altered gene expression. Moreover, we also show that growth of all five cell lines can be significantly reduced by downregulating CDK6 gene expression with small interfering RNA (siRNA. Because the majority of these breakpoints have been reported previously in MM, our results support the idea of commonmechanisms in this disease.

  16. A gene sets approach for identifying prognostic gene signatures for outcome prediction

    OpenAIRE

    Kim Yong Sung; Kim Seon-Young

    2008-01-01

    Abstract Background Gene expression profiling is a promising approach to better estimate patient prognosis; however, there are still unresolved problems, including little overlap among similarly developed gene sets and poor performance of a developed gene set in other datasets. Results We applied a gene sets approach to develop a prognostic gene set from multiple gene expression datasets. By analyzing 12 independent breast cancer gene expression datasets comprising 1,756 tissues with 2,411 pr...

  17. How Gene Patents May Inhibit Scientific Research

    Directory of Open Access Journals (Sweden)

    Campo-Engelstein, Lisa

    2015-02-01

    Full Text Available In this paper, we point out three possible ways gene patents could impede scientific research. First, gene patent laws might exacerbate the culture of secrecy ubiquitous in science. Second, gene patents may limit researchers’ ability to study poly or multigenic diseases without access to all genetic etiologies. Third, gene patents could result in a “patent thicket”.

  18. Analysis of Duplicate Genes in Soybean

    Institute of Scientific and Technical Information of China (English)

    C.M. Cai; K.J. Van; M.Y. Kim; S.H. Lee

    2007-01-01

    @@ Gene duplication is a major determinant of the size and gene complement of eukaryotic genomes (Lockton and Gaut, 2005). There are a number of different ways in which duplicate genes can arise (Sankoff, 2001), but the most spectacular method of gene duplication may be whole genome duplication via polyploidization.

  19. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric;

    2010-01-01

    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology.......In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  20. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S;

    2011-01-01

    The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere...... as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a...

  1. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne;

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... investigated by microarray analysis, and descriptive statistics were performed to evaluate the effects of 1) electroporation, 2) DNA injection, and 3) time after treatment. The biological significance of the results was assessed by gene annotation and supervised cluster analysis.Generally, electroporation...

  2. Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Seçme, Mücahit; Eroğlu, Canan; Dodurga, Yavuz; Bağcı, Gülseren

    2016-07-01

    Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was detected as 350μM at 48th hours. It is determined that oleuropein causes cell cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up-regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and caspase-3 gene expressions. Apoptotic cell ratio was found 36.4±3.27% in oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and suppressed colony numbers in ratio of 53.6±4.71%.Our results demonstrated that oleuropein can be a therapeutic agent in the treatment of neuroblastoma. PMID:27032461

  3. Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Seçme, Mücahit; Eroğlu, Canan; Dodurga, Yavuz; Bağcı, Gülseren

    2016-07-01

    Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was detected as 350 μM at 48th hours. It is determined that oleuropein causes cell cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up-regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and caspase-3 gene expressions. Apoptotic cell ratio was found 36.4 ± 3.27% in oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and suppressed colony numbers in ratio of 53.6 ± 4.71%.Our results demonstrated that oleuropein can be a therapeutic agent in the treatment of neuroblastoma.

  4. Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes in human coronary artery smooth muscle cells.

    Science.gov (United States)

    Minta, Joe; Jungwon Yun, James; St Bernard, Rosanne

    2010-01-01

    Recent studies suggest that circulating LDL (low-density lipoproteins) play a central role in the pathogenesis of atherosclerosis, and the oxidized form (ox-LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell formation and the transition of quiescent and contractile vascular SMCs (smooth muscle cells) to the migratory and proliferative phenotype. SMC phenotype transition and hyperplasia are the pivotal events in the pathogenesis of atherosclerosis. To comprehend the complex molecular mechanisms involved in ox-LDL-mediated SMC phenotype transition, we have compared the differential gene expression profiles of cultured quiescent human coronary artery SMCs with cells induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray chips. Assignment of the regulated genes into functional groups indicated that several genes involved in metabolism, membrane transport, cell-cell interactions, signal transduction, transcription, translation, cell migration, proliferation and apoptosis were differentially expressed. Our data suggests that the interaction of ox-LDL with its cognate receptors on SMCs modulates the induction of several growth factors and cytokines, which activate a variety of intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine, Rho kinase pathways) that contribute to SMC transition from the quiescent and contractile phenotype to the proliferative and migratory phenotype. Our study has also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1, MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC phenotype transition and substantially extends the list of potential candidate genes involved in atherogenesis.

  5. Altered microRNA Expression Profiles and Regulation of INK4A/CDKN2A Tumor Suppressor Genes in Canine Breast Cancer Models.

    Science.gov (United States)

    Lutful Kabir, Farruk Mohammad; DeInnocentes, Patricia; Bird, Richard Curtis

    2015-12-01

    microRNA (miRNA) expression profiling of cancer versus normal cells may reveal the characteristic regulatory features that can be correlated to altered gene expression in both human and animal models of cancers. In this study, the comprehensive expression profiles of the 277 highly characterized miRNAs from the canine genome were evaluated in spontaneous canine mammary tumor (CMT) models harboring defects in a group of cell cycle regulatory and potent tumor suppressor genes of INK4/CDKN2 family including p16/INK4A, p14ARF, and p15/INK4B. A large number of differentially expressed miRNAs were identified in three CMT cell lines to potentially target oncogenes, tumor suppressor genes and cancer biomarkers. A group of the altered miRNAs were identified by miRNA target prediction tools for regulation of the INK4/CDKN2 family tumor suppressor genes. miRNA-141 was experimentally validated for INK4A 3'-UTR target binding in the CMT cell lines providing an essential mechanism for the post-transcriptional regulation of the INK4A tumor suppressor gene in CMT models. A well-recognized group of miRNAs including miR-21, miR-155, miR-9, miR-34a, miR-143/145, and miR-31 were found to be altered in both CMTs and human breast cancer. These altered miRNAs might serve as potential targets for advancing the development of future therapeutic reagents. These findings further strengthen the validity and use of canine breast cancers as appropriate models for the study of human breast cancers. PMID:26095675

  6. Gene therapy and radiotherapy in malignant tumor

    International Nuclear Information System (INIS)

    Tumor treatment is one of the most important fields in medical research. Nowadays, a novel method which is combined gene therapy with radiotherapy plays an important role in the field of cancer research, and mainly includes immune gene therapy combined with radiotherapy, suicide gene therapy or tumor suppressor gene therapy combined with radiotherapy, antiangiogenesis gene therapy combined with radiotherapy and protective gene therapy combined with radiotherapy based on the technical features. This review summarized the current status of combined therapies of gene therapy and radiotherapy and possible mechanism. (authors)

  7. FINDING GENERIFS VIA GENE ONTOLOGY ANNOTATIONS

    OpenAIRE

    Lu, Zhiyong; Cohen, K Bretonnel; Hunter, Lawrence

    2006-01-01

    A Gene Reference Into Function (GeneRIF) is a concise phrase describing a function of a gene in the Entrez Gene database. Applying techniques from the area of natural language processing known as automatic summarization, it is possible to link the Entrez Gene database, the Gene Ontology, and the biomedical literature. A system was implemented that automatically suggests a sentence from a PubMed/MEDLINE abstract as a candidate GeneRIF by exploiting a gene’s GO annotations along with location f...

  8. Molecular Studies on Preproinsulin Gene

    Directory of Open Access Journals (Sweden)

    Sabir Sarah

    2016-01-01

    Full Text Available Insulin plays an important role in maintaining the blood glucose level of the body. The β-cells of pancreas produce insulin in the form of precursor that is preproinsulin. The gene of preproinsulin provides an interesting system for addressing question related to molecular evolution. Recombinant DNA technology has made it possible to isolate and sequence the chromosomal genes coding for unique protein products. Although preproinsulin of various organism has been isolated and cloned, but there is no report from buffalo (Bubalus bubalis that is our major livestock. The genomic DNA of buffalo was isolated using Laura-Lee-Boodram method. The part of preproinsulin gene (596bp and 520bp using BPPI-UPS and bpiful_F as forward and BC1-C as reverse primer was amplified. Cloning of amplified fragments of gene were performed in pCR 2.1 vector. Positive clones were screened on the basis of blue white selection. The band obtained on 596bp and 520bp after colony PCR confirmed the successful cloning of preproinsulin gene in pCR 2.1 vector.

  9. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  10. Clock Genes in Glia Cells

    Science.gov (United States)

    Chi-Castañeda, Donají

    2016-01-01

    Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes’ transcription, collectively known as “clock-controlled genes.” Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called “glial clocks,” since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications. PMID:27666286

  11. Advancement and prospects of tumor gene therapy

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Qing-Tao Wang; He Liu; Zhen-Zhu Zhang; Wen-Lin Huang

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucieotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.

  12. Genes Contributing to the Development of Alcoholism

    OpenAIRE

    Edenberg, Howard J

    2012-01-01

    Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. However, identifying those genes and the specific variations involved is challenging. Researchers have used both case–control and family studies to identify genes related to alcoholism risk. In addition, different strategies such as candidate gene analyses and genome-wide association studies have been used. The strongest effects have been found for specific variants of genes that...

  13. Switching on the Lights for Gene Therapy

    OpenAIRE

    Alexandra Winkeler; Miguel Sena-Esteves; Paulis, Leonie E.M.; Hongfeng Li; Yannic Waerzeggers; Benedikt Rückriem; Uwe Himmelreich; Markus Klein; Parisa Monfared; Rueger, Maria A.; Michael Heneka; Stefan Vollmar; Mathias Hoehn; Cornel Fraefel; Rudolf Graf

    2007-01-01

    Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transductio...

  14. Activities of Human Gene Nomenclature Committee

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-16

    The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

  15. Repetitive sequence environment distinguishes housekeeping genes

    OpenAIRE

    Eller, C. Daniel; Regelson, Moira; Merriman, Barry; Nelson, Stan,; Horvath, Steve; Marahrens, York

    2006-01-01

    Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear E...

  16. Concerted evolution of human amylase genes.

    OpenAIRE

    Gumucio, D L; Wiebauer, K; Caldwell, R M; Samuelson, L C; Meisler, M H

    1988-01-01

    Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, we have identified two pancreatic amylase genes and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, du...

  17. Progress in Gene Therapy for Prostate Cancer

    OpenAIRE

    KamranAliAhmed; BrianJamesDavis; TorrenceMWilson; GregoryAWiseman; MarkJFederspiel; JohnCMorris

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our...

  18. Gene Therapy in Human Breast Cancer

    OpenAIRE

    Abaan, Ogan D.

    2002-01-01

    Gene therapy, being a novel treatment for many diseases, is readily applicable for the treatment of cancer patients. Breast cancer is the most common cancer among women. There are many clinical protocols for the treatment of breast cancer, and gene therapy is now being considered within current protocols. This review will focus on the basic concepts of cancer gene therapy strategies (suicide gene, tumor suppressor gene, anti-angiogenesis, immunotherapy, oncolytic viruses and ribozyme/antisens...

  19. Gene functional similarity search tool (GFSST)

    OpenAIRE

    Russo James J; Sheng Huitao; Zhang Jinghui; Zhang Peisen; Osborne Brian; Buetow Kenneth

    2006-01-01

    Abstract Background With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. Increasing amounts of data about genes, gene products and their functions have been stored in databases. To facilitate selection of candidate genes for gene-disease research, genetic as...

  20. Novel algorithms for in vitro gene synthesis

    OpenAIRE

    Thachuk, Chris

    2007-01-01

    Methods for reliable synthesis of long genes offer great promise for novel protein synthesis via expression of synthetic genes. Current technologies use computational methods for design of short oligos, which can then be reliably synthesized and assembled into the desired target gene. A precursor to this process is optimization of the gene sequence for improved protein expression. In this thesis, we provide the first results on the computational complexity of oligo design for gene synthesis. ...

  1. Gene networks and haloperidol-induced catalepsy

    OpenAIRE

    Iancu, O. D.; Darakjian, P.; Malmanger, B.; Walter, N. A. R.; McWeeney, S.; Hitzemann, R

    2011-01-01

    The current study examined the changes in striatal gene network structure induced by short-term selective breeding from a heterogeneous stock for haloperidol response. Brain (striatum) gene expression data were obtained using the Illumina WG 8.2 array, and the datasets from responding and non-responding selected lines were independently interrogated using a weighted gene coexpression network analysis (WGCNA). We detected several gene modules (groups of coexpressed genes) in each dataset; the ...

  2. Modelling Nonstationary Gene Regulatory Processes

    Directory of Open Access Journals (Sweden)

    Marco Grzegorcyzk

    2010-01-01

    Full Text Available An important objective in systems biology is to infer gene regulatory networks from postgenomic data, and dynamic Bayesian networks have been widely applied as a popular tool to this end. The standard approach for nondiscretised data is restricted to a linear model and a homogeneous Markov chain. Recently, various generalisations based on changepoint processes and free allocation mixture models have been proposed. The former aim to relax the homogeneity assumption, whereas the latter are more flexible and, in principle, more adequate for modelling nonlinear processes. In our paper, we compare both paradigms and discuss theoretical shortcomings of the latter approach. We show that a model based on the changepoint process yields systematically better results than the free allocation model when inferring nonstationary gene regulatory processes from simulated gene expression time series. We further cross-compare the performance of both models on three biological systems: macrophages challenged with viral infection, circadian regulation in Arabidopsis thaliana, and morphogenesis in Drosophila melanogaster.

  3. The plant ADH gene family.

    Science.gov (United States)

    Strommer, Judith

    2011-04-01

    The structures, evolution and functions of alcohol dehydrogenase gene families and their products have been scrutinized for half a century. Our understanding of the enzyme structure and catalytic activity of plant alcohol dehydrogenase (ADH-P) is based on the vast amount of information available for its animal counterpart. The probable origins of the enzyme from a simple β-coil and eventual emergence from a glutathione-dependent formaldehyde dehydrogenase have been well described. There is compelling evidence that the small ADH gene families found in plants today are the survivors of multiple rounds of gene expansion and contraction. To the probable original function of their products in the terminal reaction of anaerobic fermentation have been added roles in yeast-like aerobic fermentation and the production of characteristic scents that act to attract animals that serve as pollinators or agents of seed dispersal and to protect against herbivores.

  4. Gene Technology in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Xiao-Dan Sun

    2006-01-01

    Full Text Available Scaffold, cells and signaling factors are regarded as the three essential components in tissue engineering. With the development of molecular and cell biology, gene technology is beginning to show a promising position in tissue engineering as it can influence these essential components at DNA-level. By introducing plasmid DNA or genes encoding certain signaling factors (growth factors/cytokines into the cells, required growth factors/cytokines can be expressed and secreted spatially and temporally by the transfected cells, which will promote the differentiation, proliferation and organization of the cells on the scaffold. Protein-based scaffolds which have specific structures can also be prepared genetically to induce attachment and spreading of the cells. This paper reviews research work of gene technology developed in tissue engineering.

  5. Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast

    NARCIS (Netherlands)

    Medema, Marnix H.; Takano, Eriko; Breitling, Rainer; Nowick, Katja

    2013-01-01

    The genes encoding many biomolecular systems and pathways are genomically organized in operons or gene clusters. With MultiGeneBlast, we provide a user-friendly and effective tool to perform homology searches with operons or gene clusters as basic units, instead of single genes. The contextualizatio

  6. EasyGene – a prokaryotic gene finder that ranks ORFs by statistical significance

    DEFF Research Database (Denmark)

    Larsen, Thomas Schou; Krogh, Anders Stærmose

    2003-01-01

    annotated as genes.Results: In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM) that is automatically estimated for a new genome. Using extensions of similarities...

  7. Gene Therapy for Coagulation Disorders.

    Science.gov (United States)

    Swystun, Laura L; Lillicrap, David

    2016-04-29

    Molecular genetic details of the human coagulation system were among the first successes of the genetic revolution in the 1980s. This information led to new molecular diagnostic strategies for inherited disorders of hemostasis and the development of recombinant clotting factors for the treatment of the common inherited bleeding disorders. A longer term goal of this knowledge has been the establishment of gene transfer to provide continuing access to missing or defective hemostatic proteins. Because of the relative infrequency of inherited coagulation factor disorders and the availability of safe and effective alternative means of management, the application of gene therapy for these conditions has been slow to realize clinical application. Nevertheless, the tools for effective and safe gene transfer are now much improved, and we have started to see examples of clinical gene therapy successes. Leading the way has been the use of adeno-associated virus-based strategies for factor IX gene transfer in hemophilia B. Several small phase 1/2 clinical studies using this approach have shown prolonged expression of therapeutically beneficial levels of factor IX. Nevertheless, before the application of gene therapy for coagulation disorders becomes widespread, several obstacles need to be overcome. Immunologic responses to the vector and transgenic protein need to be mitigated, and production strategies for clinical grade vectors require enhancements. There is little doubt that with the development of more efficient and facile strategies for genome editing and the application of other nucleic acid-based approaches to influence the coagulation system, the future of genetic therapies for hemostasis is bright. PMID:27126652

  8. Electroporation-mediated gene delivery.

    Science.gov (United States)

    Young, Jennifer L; Dean, David A

    2015-01-01

    Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models.

  9. Genomics of local adaptation with gene flow.

    Science.gov (United States)

    Tigano, Anna; Friesen, Vicki L

    2016-05-01

    Gene flow is a fundamental evolutionary force in adaptation that is especially important to understand as humans are rapidly changing both the natural environment and natural levels of gene flow. Theory proposes a multifaceted role for gene flow in adaptation, but it focuses mainly on the disruptive effect that gene flow has on adaptation when selection is not strong enough to prevent the loss of locally adapted alleles. The role of gene flow in adaptation is now better understood due to the recent development of both genomic models of adaptive evolution and genomic techniques, which both point to the importance of genetic architecture in the origin and maintenance of adaptation with gene flow. In this review, we discuss three main topics on the genomics of adaptation with gene flow. First, we investigate selection on migration and gene flow. Second, we discuss the three potential sources of adaptive variation in relation to the role of gene flow in the origin of adaptation. Third, we explain how local adaptation is maintained despite gene flow: we provide a synthesis of recent genomic models of adaptation, discuss the genomic mechanisms and review empirical studies on the genomics of adaptation with gene flow. Despite predictions on the disruptive effect of gene flow in adaptation, an increasing number of studies show that gene flow can promote adaptation, that local adaptations can be maintained despite high gene flow, and that genetic architecture plays a fundamental role in the origin and maintenance of local adaptation with gene flow.

  10. GeneMANIA prediction server 2013 update.

    Science.gov (United States)

    Zuberi, Khalid; Franz, Max; Rodriguez, Harold; Montojo, Jason; Lopes, Christian Tannus; Bader, Gary D; Morris, Quaid

    2013-07-01

    GeneMANIA (http://www.genemania.org) is a flexible user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. GeneMANIA can also be used in a function prediction setting: given a query gene, GeneMANIA finds a small set of genes that are most likely to share function with that gene based on their interactions with it. Enriched Gene Ontology categories among this set can sometimes point to the function of the gene. Seven organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens, Rattus norvegicus and Saccharomyces cerevisiae), and hundreds of data sets have been collected from GEO, BioGRID, IRefIndex and I2D, as well as organism-specific functional genomics data sets. Users can customize their search by selecting specific data sets to query and by uploading their own data sets to analyze. PMID:23794635

  11. A gene-based information gain method for detecting gene-gene interactions in case-control studies.

    Science.gov (United States)

    Li, Jin; Huang, Dongli; Guo, Maozu; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Zhang, Ruijie; Jiang, Yongshuai; Lv, Hongchao; Wang, Limei

    2015-11-01

    Currently, most methods for detecting gene-gene interactions (GGIs) in genome-wide association studies are divided into SNP-based methods and gene-based methods. Generally, the gene-based methods can be more powerful than SNP-based methods. Some gene-based entropy methods can only capture the linear relationship between genes. We therefore proposed a nonparametric gene-based information gain method (GBIGM) that can capture both linear relationship and nonlinear correlation between genes. Through simulation with different odds ratio, sample size and prevalence rate, GBIGM was shown to be valid and more powerful than classic KCCU method and SNP-based entropy method. In the analysis of data from 17 genes on rheumatoid arthritis, GBIGM was more effective than the other two methods as it obtains fewer significant results, which was important for biological verification. Therefore, GBIGM is a suitable and powerful tool for detecting GGIs in case-control studies.

  12. From gene to disease; hypophosphataemic rickets and the PHEX gene

    NARCIS (Netherlands)

    Jansen, M; van Dael, C.M.L.; Verrijn Stuart, A.A.; van der Hout, A.H.; Rump, P.

    2006-01-01

    X-linked hypophosphataemic rickets is associated with mutations in the PHEX gene on the short arm of the X chromosome, encoding a membrane-bound endoprotease which is predominantly expressed in osteoblasts. Defective PHEX function leaves phosphaturic peptides such as FGF23 uncleaved, enabling these

  13. Shuffling Yeast Gene Expression Data

    CERN Document Server

    Bilke, S

    2000-01-01

    A new method to sort gene expression patterns into functional groups is presented. The method is based on a sorting algorithm using a non-local similarity score, which takes all other patterns in the dataset into account. The method is therefore very robust with respect to noise. Using the expression data for yeast, we extract information about functional groups. Without prior knowledge of parameters the cell cycle regulated genes in yeast can be identified. Furthermore a second, independent cell clock is identified. The capability of the algorithm to extract information about signal flow in the regulatory network underlying the expression patterns is demonstrated.

  14. Zipf's Law in Gene Expression

    CERN Document Server

    Furusawa, C; Furusawa, Chikara; Kaneko, Kunihiko

    2002-01-01

    Using data from gene expression databases on various organisms and tissues, including yeast, nematodes, human normal and cancer tissues, and embryonic stem cells, we found that the abundances of expressed genes exhibit a power-law distribution with an exponent close to -1, i.e., they obey Zipf's law. Furthermore, by simulations of a simple model with an intra-cellular reaction network, we found that Zipf's law of chemical abundance is a universal feature of cells where such a network optimizes the efficiency and faithfulness of self-reproduction. These findings provide novel insights into the nature of the organization of reaction dynamics in living cells.

  15. Concerted evolution of human amylase genes

    Energy Technology Data Exchange (ETDEWEB)

    Gumucio, D.L.; Wiebauer, K.; Caldwell, R.M.; Samuelson, L.C.; Meisler, M.H.

    1988-03-01

    Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, the authors have identified two pancreatic amylase gene and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversion, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide - 160 and the cap site. Two sequence elements througth to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' lanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.

  16. Evidence based selection of housekeeping genes.

    Directory of Open Access Journals (Sweden)

    Hendrik J M de Jonge

    Full Text Available For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes is required. It is known that commonly used housekeeping genes (e.g. ACTB, GAPDH, HPRT1, and B2M vary considerably under different experimental conditions and therefore their use for normalization is limited. We performed a meta-analysis of 13,629 human gene array samples in order to identify the most stable expressed genes. Here we show novel candidate housekeeping genes (e.g. RPS13, RPL27, RPS20 and OAZ1 with enhanced stability among a multitude of different cell types and varying experimental conditions. None of the commonly used housekeeping genes were present in the top 50 of the most stable expressed genes. In addition, using 2,543 diverse mouse gene array samples we were able to confirm the enhanced stability of the candidate novel housekeeping genes in another mammalian species. Therefore, the identified novel candidate housekeeping genes seem to be the most appropriate choice for normalizing gene expression data.

  17. Genes and Syndromic Hearing Loss.

    Science.gov (United States)

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  18. Ethics of Gene Therapy Debated.

    Science.gov (United States)

    Borman, Stu

    1991-01-01

    Presented are the highlights of a press conference featuring biomedical ethicist LeRoy Walters of Georgetown University and attorney Andrew Kimbrell of the Foundation on Economic Trends. The opposing points of view of these two speakers serve to outline the pros and cons of the gene therapy issue. (CW)

  19. Codon Adaptation of Plastid Genes

    Science.gov (United States)

    Suzuki, Haruo; Morton, Brian R.

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  20. Codon Adaptation of Plastid Genes.

    Directory of Open Access Journals (Sweden)

    Haruo Suzuki

    Full Text Available Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes.

  1. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based indu...

  2. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology. PMID:27052691

  3. Positional cloning of deafness genes

    NARCIS (Netherlands)

    Kremer, H.; Cremers, F.P.M.

    2009-01-01

    The identification of the majority of the known causative genes involved in nonsyndromic sensorineural hearing loss (NSHL) started with linkage analysis as part of a positional cloning procedure. The human and mouse genome projects in combination with technical developments on genotyping, transcript

  4. What drives plant stress genes?

    NARCIS (Netherlands)

    Aarts, M.G.M.; Fiers, M.W.E.J.

    2003-01-01

    Currently, there is a lot of interest in the plant stress response. Using large-scale genomics approaches, more and more genes are being identified that are involved in or even regulate this complex process. The recent boost in expression profile analyses for several plant stress responses has enabl

  5. Gene Expression in Trypanosomatid Parasites

    Directory of Open Access Journals (Sweden)

    Santiago Martínez-Calvillo

    2010-01-01

    Full Text Available The parasites Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids. In silico analyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

  6. Statistical Approach to Gene Evolution

    CERN Document Server

    Chattopadhyay, S; Chakrabarti, J; Chattopadhyay, Sujay; Kanner, William A.; Chakrabarti, Jayprokas

    2001-01-01

    The evolution in coding DNA sequences brings new flexibility and freedom to the codon words, even as the underlying nucleotides get significantly ordered. These curious contra-rules of gene organisation are observed from the distribution of words and the second moments of the nucleotide letters. These statistical data give us the physics behind the classification of bacteria.

  7. Genes, Environment, and Human Behavior.

    Science.gov (United States)

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  8. Codon Adaptation of Plastid Genes.

    Science.gov (United States)

    Suzuki, Haruo; Morton, Brian R

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  9. Buffering in cyclic gene networks

    Science.gov (United States)

    Glyzin, S. D.; Kolesov, A. Yu.; Rozov, N. Kh.

    2016-06-01

    We consider cyclic chains of unidirectionally coupled delay differential-difference equations that are mathematical models of artificial oscillating gene networks. We establish that the buffering phenomenon is realized in these system for an appropriate choice of the parameters: any given finite number of stable periodic motions of a special type, the so-called traveling waves, coexist.

  10. RCDB: Renal Cancer Gene Database

    Directory of Open Access Journals (Sweden)

    Ramana Jayashree

    2012-05-01

    Full Text Available Abstract Background Renal cell carcinoma or RCC is one of the common and most lethal urological cancers, with 40% of the patients succumbing to death because of metastatic progression of the disease. Treatment of metastatic RCC remains highly challenging because of its resistance to chemotherapy as well as radiotherapy, besides surgical resection. Whereas RCC comprises tumors with differing histological types, clear cell RCC remains the most common. A major problem in the clinical management of patients presenting with localized ccRCC is the inability to determine tumor aggressiveness and accurately predict the risk of metastasis following surgery. As a measure to improve the diagnosis and prognosis of RCC, researchers have identified several molecular markers through a number of techniques. However the wealth of information available is scattered in literature and not easily amenable to data-mining. To reduce this gap, this work describes a comprehensive repository called Renal Cancer Gene Database, as an integrated gateway to study renal cancer related data. Findings Renal Cancer Gene Database is a manually curated compendium of 240 protein-coding and 269 miRNA genes contributing to the etiology and pathogenesis of various forms of renal cell carcinomas. The protein coding genes have been classified according to the kind of gene alteration observed in RCC. RCDB also includes the miRNAsdysregulated in RCC, along with the corresponding information regarding the type of RCC and/or metastatic or prognostic significance. While some of the miRNA genes showed an association with other types of cancers few were unique to RCC. Users can query the database using keywords, category and chromosomal location of the genes. The knowledgebase can be freely accessed via a user-friendly web interface at http://www.juit.ac.in/attachments/jsr/rcdb/homenew.html. Conclusions It is hoped that this database would serve as a useful complement to the existing public

  11. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  12. Delineating an Epigenetic Continuum for Initiation, Transformation and Progression to Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kang Mei; Stephen, Josena K. [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Raju, Usha [Department of Pathology, Henry Ford Hospital, Detroit, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Worsham, Maria J., E-mail: mworsha1@hfhs.org [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States)

    2011-03-29

    Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised 17 breast cancer patients with multiple benign and/or in situ lesions concurrently present with invasive carcinoma within a tumor biopsy. DNA from tumor tissue, normal breast epithelium when present, benign lesions (fibroadenoma, hyperplasia, papilloma, sclerosing adenosis, apocrine metaplasia, atypical lobular hyperplasia or atypical ductal hyperplasia), and in situ lesions of lobular carcinoma and ductal carcinoma were interrogated for promoter methylation status in 22 tumor suppressor genes using the multiplex ligation-dependent probe amplification assay (MS-MLPA). Methylation specific PCR was performed to confirm hypermethylation detected by MS-MLPA. Promoter methylation was detected in 11/22 tumor suppressor genes in 16/17 cases. Hypermethylation of RASSF1 was most frequent, present in 14/17 cases, followed by APC in 12/17, and GSTP1 in 9/17 cases with establishment of an epigenetic monocloncal progression continuum to invasive breast cancer. Hypermethylated promoter regions in normal breast epithelium, benign, and premalignant lesions within the same tumor biopsy implicate RASSF1, APC, GSTP1, TIMP3, CDKN2B, CDKN2A, ESR1, CDH13, RARB, CASP8, and TP73 as early events. DNA hypermethylation underlies the pathogenesis of step-wise transformation along a monoclonal continuum from normal to preneoplasia to invasive breast cancer.

  13. Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR

    OpenAIRE

    Thein Swee; Jiang Jie; Best Steve; Silver Nicholas

    2006-01-01

    Abstract Background Control genes, which are often referred to as housekeeping genes, are frequently used to normalise mRNA levels between different samples. However, the expression level of these genes may vary among tissues or cells and may change under certain circumstances. Thus, the selection of housekeeping genes is critical for gene expression studies. To address this issue, 7 candidate housekeeping genes including several commonly used ones were investigated in isolated human reticulo...

  14. Discovering Implicit Entity Relation with the Gene-Citation-Gene Network

    OpenAIRE

    Min Song; Nam-Gi Han; Yong-Hwan Kim; Ying Ding; Tamy Chambers

    2013-01-01

    In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG) network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG) network constructed over the same corpus but which uses gene pairs explicitly connected through traditional c...

  15. Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps

    OpenAIRE

    An, Li; Obradovic, Zoran; Smith, Desmond; Bodenreider, Olivier; Megalooikonomou, Vasileios

    2009-01-01

    Association rules mining methods have been recently applied to gene expression data analysis to reveal relationships between genes and different conditions and features. However, not much effort has focused on detecting the relation between gene expression maps and related gene functions. Here we describe such an approach to mine association rules among gene functions in clusters of similar gene expression maps on mouse brain. The experimental results show that the detected association rules ...

  16. Gene expression profiles in skeletal muscle after gene electrotransfer

    Directory of Open Access Journals (Sweden)

    Eriksen Jens

    2007-06-01

    Full Text Available Abstract Background Gene transfer by electroporation (DNA electrotransfer to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 μs followed by a long low voltage pulse (LV, 100 V/cm, 400 ms; a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP and excised at 4 hours, 48 hours or 3 weeks after treatment. Results Differentially expressed genes were investigated by microarray analysis, and descriptive statistics were performed to evaluate the effects of 1 electroporation, 2 DNA injection, and 3 time after treatment. The biological significance of the results was assessed by gene annotation and supervised cluster analysis. Generally, electroporation caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related with the control muscles. Most interestingly, no changes in the expression of proteins involved in inflammatory responses or muscle regeneration was detected, indicating limited muscle damage and regeneration. Histological analysis revealed structural changes with loss of cell integrity and striation pattern in some fibres after DNA+HV+LV treatment, while HV+LV pulses alone showed preservation of cell integrity. No difference in the force generation capacity was observed in

  17. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  18. Transferring alien genes to wheat

    International Nuclear Information System (INIS)

    In broad terms an alien gene can be considered to be any gene transferred to wheat from a related species. As described above by Maan (section 7D) the genus Triticum contains a broad range of species, some of which cross readily with the cultivated tetraploid (T. Turgidum L.) or hexaploid (T. aestivum L.) wheats, and others only with great difficulty. In addition, wheat will also cross with species in a number of other genera including Agropyron, Elymus, Elytrigia (=Agropyron), Haynaldia, Hordeum, and Secale (Riley and Kimber, 1966; Knobloch, 1968; Feldman and Sears, 1981). In discussing the Triticum and Aegilops spp., the classification by Kimber and Sears, section SA-I, above, will be followed. For the Agropyron and related species the classification described by Dewey (1983) will be used. To avoid confusion, in referring to the literature the designations used by the authors will be given, followed by the new designation. The wild relatives of wheat are adapted to a broad range of environments and carry a large reservoir of useful genes (Zohary et al., 1969; Kerber and Dyck, 1973; Brezhnev, 1977; Feldman and Sears, 1981; Limin and Fowler, 1981; Sharma et aI., 1981; McGuire and Dvorak, 1981). Initially they were considered to be primarily sources of disease resistance, but more recently they have been recognized as potential sources of genes for high protein, cold tolerance, salt tolerance, drought tolerance, lodging resistance, early maturity, and even yield. Extensive screening of the wild relatives of wheat needs to be done before their useful genes can be fully utilized

  19. Msx homeobox gene family and craniofacial development

    Institute of Scientific and Technical Information of China (English)

    SYLVIA ALAPPAT; ZUN YI ZHANG; YI PING CHEN

    2003-01-01

    Vertebrate Msx genes are unlinked,homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene.These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development.Inductive interactions mediated by the Msx genes are essential for normal craniofacial,limb and ectodermal organ morphogenesis,and are also essential to survival in mice,as manifested by the phenotypic abnormalities shown in knockout mice and in humans.This review summarizes studies on the expression,regulation,and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice.

  20. Gene doping: the hype and the harm.

    Science.gov (United States)

    McKanna, Trudy A; Toriello, Helga V

    2010-06-01

    "Gene doping" is the term used to describe the potential abuse of gene therapy as a performance-enhancing agent. Gene doping would apply the techniques used in gene therapy to provide altered expression of genes that would promote physical superiority. For example, insulin-like growth factor 1 (IGF-1) is a primary target for growth hormone; overexpression of IGF-1 can lead to increased muscle mass and power. Although gene doping is still largely theoretical, its implications for sports, health, ethics, and medical genetics are significant.

  1. Delivery of genes into the CF airway.

    Science.gov (United States)

    Gill, Deborah R; Hyde, Stephen C

    2014-10-01

    Gene therapy was suggested as a potential treatment for cystic fibrosis (CF), even before the identification of the CFTR gene. Initial enthusiasm has been tempered as it became apparent that reintroduction of the CFTR gene into the cells of the lung is more difficult than anticipated. Here, we review the major gene delivery vectors evaluated clinically, and suggest that advances in either plasmid DNA design and/or hybrid lentivirus biology may finally facilitate lung gene transfer with efficiencies sufficient for CF gene therapy to offer clinical benefit. PMID:25015239

  2. Gene doping: the hype and the harm.

    Science.gov (United States)

    McKanna, Trudy A; Toriello, Helga V

    2010-06-01

    "Gene doping" is the term used to describe the potential abuse of gene therapy as a performance-enhancing agent. Gene doping would apply the techniques used in gene therapy to provide altered expression of genes that would promote physical superiority. For example, insulin-like growth factor 1 (IGF-1) is a primary target for growth hormone; overexpression of IGF-1 can lead to increased muscle mass and power. Although gene doping is still largely theoretical, its implications for sports, health, ethics, and medical genetics are significant. PMID:20538153

  3. Gene therapy and its implications in Periodontics

    Directory of Open Access Journals (Sweden)

    Mahale Swapna

    2009-01-01

    Full Text Available Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here.

  4. The P450 gene superfamily: recommended nomenclature.

    Science.gov (United States)

    Nebert, D W; Adesnik, M; Coon, M J; Estabrook, R W; Gonzalez, F J; Guengerich, F P; Gunsalus, I C; Johnson, E F; Kemper, B; Levin, W

    1987-02-01

    A nomenclature for the P450 gene superfamily is proposed based on evolution. Recommendations include Roman numerals for distinct gene families, capital letters for subfamilies, and Arabic numerals for individual genes. An updating of this list, which presently includes 65 entries, will be required every 1-2 years. Assignment of orthologous genes is presently uncertain in some cases--between widely diverged species and especially in the P450II family due to the large number of genes. As more is known, it might become necessary to change some gene assignments that are based on our present knowledge. PMID:3829886

  5. The Nme gene family in fish.

    OpenAIRE

    Desvignes, T.; FOSTIER, A.; Fauvel, C.; Bobe, J

    2013-01-01

    The Nme gene family, also known as Nm23 or NDPK, is a very ancient gene family that can be found in all kingdoms of life. In the late eighties, a gene of the Nme family, NME1, was identified as the first metastatic suppressor gene, resulting in a major interest for this family. Due to the complexity of the family, the need for a unified and evolutionary-supported gene nomenclature was recently stressed by the scientific community. Based on a complete evolutionary history study of the gene fam...

  6. Polypeptide composition and gag gene-coded products of type-D oncovirus from HEp-2 cells.

    Science.gov (United States)

    Morozov, V A

    1982-01-01

    The protein composition of type-D oncovirus HEp-2, isolated from cell-free medium of continuous human HEp-2 cell line, has been investigated using electrophoresis on gradient polyacrylamide gels with sodium dodecyl sulfate (SDS). Labeling with 14C-amino acids revealed five viral polypeptides with molecular weights of 70 000 (gp70), 27 000 (p27), 19 000 (p19), 15 000 (p15), 12 000-10 000 (p12-10). The 70 000 dalton protein was shown to be the only glycoprotein by incorporation of radioactive glucosamine. A polypeptide with molecular weight of 78 000 has been specifically precipitated from pulse-labeled type-D oncovirus producing HEp-2 cells with goat anti Mason-Pfizer p27 serum. This protein was shown to be gag gene-coded polyprotein precursor (Pr78gag) of the major virus polypeptide p27. Pulse-labeled HEp-2 and Mason-Pfizer infected Tu 197 cells were rinsed, lysed, clarified and precipitated with goat anti Mason-Pfizer p27 serum. In both cases Pr78gag was detected.

  7. Detection of gene expression pattern in the early stage after spinal cord injury by gene chip

    Institute of Scientific and Technical Information of China (English)

    刘成龙; 靳安民; 童斌辉

    2003-01-01

    Objective: To study the changes of the gene expression pattern of spinal cord tissues in the early stage after injury by DNA microarray (gene chip). Methods: The contusion model of rat spinal cord was established according to Allen's falling strike method and the gene expression patterns of normal and injured spinal cord tissues were studied by gene chip. Results: The expression of 45 genes was significantly changed in the early stage after spinal cord injury, in which 22 genes up-regulated and 23 genes down-regulated. Conclusions: The expression of some genes changes significantly in the early stage after spinal cord injury, which indicates the complexity of secondary spinal cord injury.

  8. GenePRIMP: A GENE PRediction IMprovement Pipeline for Prokaryotic genomes

    Energy Technology Data Exchange (ETDEWEB)

    Pati, Amrita; Ivanova, Natalia N.; Mikhailova, Natalia; Ovchinnikova, Galina; Hooper, Sean D.; Lykidis, Athanasios; Kyrpides, Nikos C.

    2010-04-01

    We present 'gene prediction improvement pipeline' (GenePRIMP; http://geneprimp.jgi-psf.org/), a computational process that performs evidence-based evaluation of gene models in prokaryotic genomes and reports anomalies including inconsistent start sites, missed genes and split genes. We found that manual curation of gene models using the anomaly reports generated by GenePRIMP improved their quality, and demonstrate the applicability of GenePRIMP in improving finishing quality and comparing different genome-sequencing and annotation technologies.

  9. Y-chromosomal diversity in Haiti and Jamaica: contrasting levels of sex-biased gene flow.

    Science.gov (United States)

    Simms, Tanya M; Wright, Marisil R; Hernandez, Michelle; Perez, Omar A; Ramirez, Evelyn C; Martinez, Emanuel; Herrera, Rene J

    2012-08-01

    Although previous studies have characterized the genetic structure of populations from Haiti and Jamaica using classical and autosomal STR polymorphisms, the patrilineal influences that are present in these countries have yet to be explored. To address this lacuna, the current study aims to investigate, for the first time, the potential impact of different ancestral sources, unique colonial histories, and distinct family structures on the paternal profile of both groups. According to previous reports examining populations from the Americas, island-specific demographic histories can greatly impact population structure, including various patterns of sex-biased gene flow. Also, given the contrasting autosomal profiles provided in our earlier study (Simms et al.: Am J Phys Anthropol 142 (2010) 49-66), we hypothesize that the degree and directionality of gene flow from Europeans, Africans, Amerindians, and East Asians are dissimilar in the two countries. To test this premise, 177 high-resolution Y-chromosome binary markers and 17 Y-STR loci were typed in Haiti (n = 123) and Jamaica (n = 159) and subsequently utilized for phylogenetic comparisons to available reference collections encompassing Africa, Europe, Asia (East and South), and the New World. Our results reveal that both studied populations exhibit a predominantly South-Saharan paternal component, with haplogroups A1b-V152, A3-M32, B2-M182, E1a-M33, E1b1a-M2, E2b-M98, and R1b2-V88 comprising 77.2% and 66.7% of the Haitian and Jamaican paternal gene pools, respectively. Yet, European derived chromosomes (i.e., haplogroups G2a*-P15, I-M258, R1b1b-M269, and T-M184) were detected at commensurate levels in Haiti (20.3%) and Jamaica (18.9%), whereas Y-haplogroups indicative of Chinese [O-M175 (3.8%)] and Indian [H-M69 (0.6%) and L-M20 (0.6%)] ancestry were restricted to Jamaica. PMID:22576450

  10. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

    Science.gov (United States)

    Choi, Y-W; Bae, S M; Kim, Y-W; Lee, H N; Kim, Y W; Park, T C; Ro, D Y; Shin, J C; Shin, S J; Seo, J-S; Ahn, W S

    2007-01-01

    Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

  11. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".

    Directory of Open Access Journals (Sweden)

    Sharon E Johnatty

    2010-07-01

    Full Text Available We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC. In the discovery stage, cases with epithelial ovarian cancer (n=675 and controls (n=1,162 were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-alleleor=0.5. However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele=0.03. Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04-1.24 p=0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.

  12. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  13. GENE THERAPY AND ITS IMPLICATIONS IN SPORTS

    Directory of Open Access Journals (Sweden)

    Biljana Vitošević

    2011-06-01

    Full Text Available Thanks to the very successful Human Genome Project and the identification of genes involved in genetic disease, we now have the ability to treat many conditions. However, the identification of the genes which code certain phenotype characteristics has opened the way for abuse in the fields of sport and physical exercise. The principles of gene therapy and the ways in which genes are transferred have completely been copied from gene therapy and are now being used to increase the physical abilities of athletes. The genes most frequently used by athletes include: the the ACE gene, the ACTN3 gene, myostatin, the erythropoietin gene, PPAR-delta and the like. The misuse of these genes with the aim of increasing physical abilities has already become part of sport and is extremely difficult to identify, since genes and gene sequences entering the human body are proteins that are already struc-tural and functional parts of the organism. On the other hand, viral vectors as the instruments for gene transfer attack and destroy the human immune system, and the reaction of the human body can be negative, with a danger of insertional mutagenesis and the appearance of oncogenes. Gene ther-apy might actually be much more useful in treating sports injuries, but even these procedures are still far from clinical practice. There is a fine line between gene therapy and gene doping in athletes. A number of growth factors will enhance repair, but it happen that expression of these factors increase the strength of bones and tendons, so that giving an adventage to competitors. First of all, it is neces-sary to acquaint athletes as much as possible with the negative consequences of using gene therapy. However victory and glory may be strong achievements, the health of these young people, and respect for fundamental and ethical principles, humanity, and fair play game have a more lasting value and represent the heavier weight on the scales.

  14. Thesaurus-based disambiguation of gene symbols

    Directory of Open Access Journals (Sweden)

    Wain Hester M

    2005-06-01

    Full Text Available Abstract Background Massive text mining of the biological literature holds great promise of relating disparate information and discovering new knowledge. However, disambiguation of gene symbols is a major bottleneck. Results We developed a simple thesaurus-based disambiguation algorithm that can operate with very little training data. The thesaurus comprises the information from five human genetic databases and MeSH. The extent of the homonym problem for human gene symbols is shown to be substantial (33% of the genes in our combined thesaurus had one or more ambiguous symbols, not only because one symbol can refer to multiple genes, but also because a gene symbol can have many non-gene meanings. A test set of 52,529 Medline abstracts, containing 690 ambiguous human gene symbols taken from OMIM, was automatically generated. Overall accuracy of the disambiguation algorithm was up to 92.7% on the test set. Conclusion The ambiguity of human gene symbols is substantial, not only because one symbol may denote multiple genes but particularly because many symbols have other, non-gene meanings. The proposed disambiguation approach resolves most ambiguities in our test set with high accuracy, including the important gene/not a gene decisions. The algorithm is fast and scalable, enabling gene-symbol disambiguation in massive text mining applications.

  15. Structures of two molluscan hemocyanin genes: significance for gene evolution.

    Science.gov (United States)

    Lieb, B; Altenhein, B; Markl, J; Vincent, A; van Olden, E; van Holde, K E; Miller, K I

    2001-04-10

    We present here the description of genes coding for molluscan hemocyanins. Two distantly related mollusks, Haliotis tuberculata and Octopus dofleini, were studied. The typical architecture of a molluscan hemocyanin subunit, which is a string of seven or eight globular functional units (FUs, designated a to h, about 50 kDa each), is reflected by the gene organization: a series of eight structurally related coding regions in Haliotis, corresponding to FU-a to FU-h, with seven highly variable linker introns of 174 to 3,198 bp length (all in phase 1). In Octopus seven coding regions (FU-a to FU-g) are found, separated by phase 1 introns varying in length from 100 bp to 910 bp. Both genes exhibit typical signal (export) sequences, and in both cases these are interrupted by an additional intron. Each gene also contains an intron between signal peptide and FU-a and in the 3' untranslated region. Of special relevance for evolutionary considerations are introns interrupting those regions that encode a discrete functional unit. We found that five of the eight FUs in Haliotis each are encoded by a single exon, whereas FU-f, FU-g, and FU-a are encoded by two, three and four exons, respectively. Similarly, in Octopus four of the FUs each correspond to an uninterrupted exon, whereas FU-b, FU-e, and FU-f each contain a single intron. Although the positioning of the introns between FUs is highly conserved in the two mollusks, the introns within FUs show no relationship either in location nor phase. It is proposed that the introns between FUs were generated as the eight-unit polypeptide evolved from a monomeric precursor, and that the internal introns have been added later. A hypothesis for evolution of the ring-like quaternary structure of molluscan hemocyanins is presented. PMID:11287637

  16. Sequence and gene expression evolution of paralogous genes in willows.

    Science.gov (United States)

    Harikrishnan, Srilakshmy L; Pucholt, Pascal; Berlin, Sofia

    2015-12-22

    Whole genome duplications (WGD) have had strong impacts on species diversification by triggering evolutionary novelties, however, relatively little is known about the balance between gene loss and forces involved in the retention of duplicated genes originating from a WGD. We analyzed putative Salicoid duplicates in willows, originating from the Salicoid WGD, which took place more than 45 Mya. Contigs were constructed by de novo assembly of RNA-seq data derived from leaves and roots from two genotypes. Among the 48,508 contigs, 3,778 pairs were, based on fourfold synonymous third-codon transversion rates and syntenic positions, predicted to be Salicoid duplicates. Both copies were in most cases expressed in both tissues and 74% were significantly differentially expressed. Mean Ka/Ks was 0.23, suggesting that the Salicoid duplicates are evolving by purifying selection. Gene Ontology enrichment analyses showed that functions related to DNA- and nucleic acid binding were over-represented among the non-differentially expressed Salicoid duplicates, while functions related to biosynthesis and metabolism were over-represented among the differentially expressed Salicoid duplicates. We propose that the differentially expressed Salicoid duplicates are regulatory neo- and/or subfunctionalized, while the non-differentially expressed are dose sensitive, hence, functionally conserved. Multiple evolutionary processes, thus drive the retention of Salicoid duplicates in willows.

  17. ETS-related transcription factors ETV4 and ETV5 are involved in proliferation and induction of differentiation-associated genes in embryonic stem (ES) cells.

    Science.gov (United States)

    Akagi, Tadayuki; Kuure, Satu; Uranishi, Kousuke; Koide, Hiroshi; Costantini, Frank; Yokota, Takashi

    2015-09-11

    The pluripotency and self-renewal capacity of embryonic stem (ES) cells is regulated by several transcription factors. Here, we show that the ETS-related transcription factors Etv4 and Etv5 (Etv4/5) are specifically expressed in undifferentiated ES cells, and suppression of Oct3/4 results in down-regulation of Etv4/5. Simultaneous deletion of Etv4 and Etv5 (Etv4/5 double knock-out (dKO)) in ES cells resulted in a flat, epithelial cell-like appearance, whereas the morphology changed into compact colonies in a 2i medium (containing two inhibitors for GSK3 and MEK/ERK). Expression levels of self-renewal marker genes, including Oct3/4 and Nanog, were similar between wild-type and dKO ES cells, whereas proliferation of Etv4/5 dKO ES cells was decreased with overexpression of cyclin-dependent kinase inhibitors (p16/p19, p15, and p57). A differentiation assay revealed that the embryoid bodies derived from Etv4/5 dKO ES cells were smaller than the control, and expression of ectoderm marker genes, including Fgf5, Sox1, and Pax3, was not induced in dKO-derived embryoid bodies. Microarray analysis demonstrated that stem cell-related genes, including Tcf15, Gbx2, Lrh1, Zic3, and Baf60c, were significantly repressed in Etv4/5 dKO ES cells. The artificial expression of Etv4 and/or Etv5 in Etv4/5 dKO ES cells induced re-expression of Tcf15 and Gbx2. These results indicate that Etv4 and Etv5, potentially through regulation of Gbx2 and Tcf15, are involved in the ES cell proliferation and induction of differentiation-associated genes in ES cells.

  18. Progress in Chimeric Vector and Chimeric Gene Based Cardiovascular Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    HU Chun-Song; YOON Young-sup; ISNER Jeffrey M.; LOSORDO Douglas W.

    2003-01-01

    Gene therapy for cardiovascular diseases has developed from preliminary animal experiments to clinical trials. However, vectors and target genes used currently in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene. Each vector system has a series of advantages and limitations. Chimeric vectors which combine the advantages of viral and nonviral vector,chimeric target genes which combine two or more target genes and novel gene delivery modes are being developed. In this article, we summarized the progress in chimeric vectors and chimeric genes based cardiovascular gene therapy, which including proliferative or occlusive vascular diseases such as atheroslerosis and restenosis, hypertonic vascular disease such as hypertension and cardiac diseases such as myocardium ischemia, dilated cardiomyopathy and heart failure, even heart transplantation. The development of chimeric vector, chimeric gene and their cardiovascular gene therapy is promising.

  19. Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

    Energy Technology Data Exchange (ETDEWEB)

    Picoli Souza, K. de [Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-06-24

    Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

  20. Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

    Directory of Open Access Journals (Sweden)

    K. de Picoli Souza

    2014-08-01

    Full Text Available Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g and triiodothyronine (0.5-50 µg/100 g for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold. Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60% ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold, and decreased heart rate (5%, fast muscle myoglobin mRNA (30% and body weight (20% in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30% and body weight (14%. These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

  1. Alzheimer's Gene May Show Effects in Childhood

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159854.html Alzheimer's Gene May Show Effects in Childhood Brain scans ... 13, 2016 (HealthDay News) -- A gene related to Alzheimer's disease may start to show effects on brain ...

  2. Five New Genes Linked to Colon Cancer

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_159556.html Five New Genes Linked to Colon Cancer But researchers say it's ... 2016 (HealthDay News) -- Scientists have identified five new gene mutations that may be tied to colon cancer. ...

  3. In The Genes? Searching for Methuselah

    Science.gov (United States)

    ... Current Issue Past Issues Special Section In The Genes? Searching for Methuselah Past Issues / Winter 2007 Table ... 18 million effort to learn more about the genes, lifestyle or other factors that contribute to long, ...

  4. Bioinformatics methods for identifying candidate disease genes

    NARCIS (Netherlands)

    Driel, M.A. van; Brunner, H.G.

    2006-01-01

    With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes. Combining positional information with disease characteristics and functional information i

  5. NIH Researchers Identify OCD Risk Gene

    Science.gov (United States)

    ... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

  6. Mutation analysis of the preproghrelin gene

    DEFF Research Database (Denmark)

    Larsen, Lesli H; Gjesing, Anette P; Sørensen, Thorkild I A;

    2005-01-01

    To investigate the preproghrelin gene for variants and their association with obesity and type 2 diabetes.......To investigate the preproghrelin gene for variants and their association with obesity and type 2 diabetes....

  7. Researchers Pinpoint More Genes Linked to Vitiligo

    Science.gov (United States)

    ... 161452.html Researchers Pinpoint More Genes Linked to Vitiligo Genetic clues to this autoimmune disease could lead ... identified more genes linked to the autoimmune disease vitiligo, which causes patches of white skin and hair. ...

  8. Cattle Candidate Genes for Milk Production Traits

    OpenAIRE

    Kadlec, Tomáš

    2012-01-01

    The aim of this thesis is to make an overview of important candidate genes affecting milk yield and milk quality parameters, with an emphasis on genes associated with the quantity and quality of milk proteins and milk fat.

  9. Biodegradable nanoparticles for gene therapy technology

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@mail.ntust.edu.tw; He, Wen-Jie [National Taiwan University of Science and Technology (Taiwan Tech), Graduate Institute of Biomedical Engineering (China); Chiang, Chiao-Hsi [School of Pharmacy, National Defense Medical Center (China); Hong, Po-Da [National Taiwan University of Science and Technology (Taiwan Tech), Graduate Institute of Biomedical Engineering (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [The Hebrew University of Jerusalem, Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Center for Nanoscience and Nanotechnology and The Alex Grass Center for Drug Design and Synthesis (Israel); Ou, Keng-Liang [College of Oral Medicine, Taipei Medical University, Research Center for Biomedical Devices and Prototyping Production (China)

    2013-07-15

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes.

  10. Biodegradable nanoparticles for gene therapy technology

    International Nuclear Information System (INIS)

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes

  11. Immunoglobulins and immunoglobulin genes of the horse.

    Science.gov (United States)

    Wagner, Bettina

    2006-01-01

    Antibodies of the horse were studied intensively by many notable immunologists throughout the past century until the early 1970's. After a large gap of interest in horse immunology, additional basic studies on horse immunoglobulin genes performed during the past 10 years have resulted in new insights into the equine humoral immune system. These include the characterization of the immunoglobulin lambda and kappa light chain genes, the immunoglobulin heavy chain constant (IGHC) gene regions, and initial studies regarding the heavy chain variable genes. Horses express predominately lambda light chains and seem to have a relatively restricted germline repertoire of both lambda and kappa chain variable genes. The IGHC region contains eleven constant heavy chain genes, seven of which are gamma heavy chain genes. It is suggested that all seven genes encoding IgG isotypes are expressed and have distinct functions in equine immune responses.

  12. 'Sunscreen' Gene May Guard Against Skin Cancer

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_158935.html 'Sunscreen' Gene May Guard Against Skin Cancer Researchers hope their ... say they've identified a so-called "sunscreen" gene that may help protect against skin cancer. They ...

  13. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

    Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

  14. Bimodal gene expression patterns in breast cancer

    OpenAIRE

    Nikolsky Yuri; Bugrim Andrej; Shi Weiwei; Kirillov Eugene; Bessarabova Marina; Nikolskaya Tatiana

    2010-01-01

    Abstract We identified a set of genes with an unexpected bimodal distribution among breast cancer patients in multiple studies. The property of bimodality seems to be common, as these genes were found on multiple microarray platforms and in studies with different end-points and patient cohorts. Bimodal genes tend to cluster into small groups of four to six genes with synchronised expression within the group (but not between the groups), which makes them good candidates for robust conditional ...

  15. Organization of an echinoderm Hox gene cluster

    OpenAIRE

    Martinez, Pedro; Rast, Jonathan P.; Arenas-Mena, César; Davidson, Eric H.

    1999-01-01

    The Strongylocentrotus purpuratus genome contains a single ten-gene Hox complex >0.5 megabase in length. This complex was isolated on overlapping bacterial artificial chromosome and P1 artificial chromosome genomic recombinants by using probes for individual genes and by genomic walking. Echinoderm Hox genes of Paralog Groups (PG) 1 and 2 are reported. The cluster includes genes representing all paralog groups of vertebrate Hox clusters, except that there is a sing...

  16. Quality Measures for Gene Expression Biclusters

    OpenAIRE

    Beatriz Pontes; Ral Girldez; Aguilar-Ruiz, Jess S.

    2015-01-01

    An noticeable number of biclustering approaches have been proposed proposed for the study of gene expression data, especially for discovering functionally related gene sets under different subsets of experimental conditions. In this context, recognizing groups of co-expressed or co-regulated genes, that is, genes which follow a similar expression pattern, is one of the main objectives. Due to the problem complexity, heuristic searches are usually used instead of exhaustive algorithms. Further...

  17. Gene therapy and its implications in Periodontics

    OpenAIRE

    Mahale Swapna; Dani Nitin; Ansari Shumaila; Kale Triveni

    2009-01-01

    Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense...

  18. Topological Features In Cancer Gene Expression Data

    OpenAIRE

    Lockwood, Svetlana; Krishnamoorthy, Bala

    2014-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topologic...

  19. Gene Therapy Used in Cancer Treatment

    OpenAIRE

    Thomas Wirth; Seppo Ylä-Herttuala

    2014-01-01

    Cancer has been, from the beginning, a target of intense research for gene therapy approaches. Currently, more than 60% of all on-going clinical gene therapy trials worldwide are targeting cancer. Indeed, there is a clear unmet medical need for novel therapies. This is further urged by the fact that current conventional cancer therapies are frequently troubled by their toxicities. Different gene therapy strategies have been employed for cancer, such as pro-drug activating suicide gene therapy...

  20. Gensko zdravljenje raka: Cancer gene therapy:

    OpenAIRE

    Serša, Gregor; Čemažar, Maja; KOČEVAR, NINA

    2010-01-01

    Gene therapy uses genes to treat diseases. Large amount of research is based on cancer because current methods for cancer treatment have limited efficiencyand unwanted side effects. In the following article we first presentthe basic principles of gene therapy. Next, we describe the main delivery systems, which are viral and non-viral, and then the main therapeuticstrategies of cancer gene therapy. These can be divided into immunological, where we take advantage of the immune system for cancer...

  1. The evolution of heart gene delivery vectors

    OpenAIRE

    Wasala, Nalinda B.; Shin, Jin-Hong; Duan, Dongsheng

    2011-01-01

    Gene therapy holds promise for treating numerous heart diseases. A key premise for the success of cardiac gene therapy is the development of powerful gene transfer vehicles that can achieve highly efficient and persistent gene transfer specifically in the heart. Other features of an ideal vector include negligible toxicity, minimal immunogenicity and easy manufacturing. Rapid progress in the fields of molecular biology and virology has offered great opportunities to engineer various genetic m...

  2. Regulation of the genes involved in nitrification.

    Energy Technology Data Exchange (ETDEWEB)

    Arp, D.J.; Sayavedra-Soto, L.A.

    2003-08-14

    OAK-B135 This project focuses on the characterization of the regulation of the genes involved in nitrification in the bacterium Nitrosomonas europaea. The key genes in the nitrification pathway, amo and hao, are present in multiple copies in the genome. The promoters for these genes were identified and characterized. It was shown that there were some differences in the transcriptional regulation of the copies of these genes.

  3. Alcoholism and Alternative Splicing of Candidate Genes

    OpenAIRE

    Toshikazu Sasabe; Shoichi Ishiura

    2010-01-01

    Gene expression studies have shown that expression patterns of several genes have changed during the development of alcoholism. Gene expression is regulated not only at the level of transcription but also through alternative splicing of pre-mRNA. In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor) may form the basis of the mechanisms underlying the pathophysiology of alcoholism. These reports sugg...

  4. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    transporters G5 and G8, Niemann-Pick C1-Like protein 1, sortilin-1, ABO blood-group glycosyltransferases, myosin regulatory light chain-interacting protein and cholesterol 7α-hydroxylase have all consistently been associated with LDL cholesterol levels and/or coronary artery disease in GWAS. Whole...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol....... Novel genes in LDL metabolism will improve our understanding of mechanisms in LDL metabolism, and may lead to the identification of new drug targets to reduce LDL cholesterol levels....

  5. Gene Therapy : myth or reality ?

    OpenAIRE

    Fischer, Alain

    2016-01-01

    International audience; Gene therapy has become a reality, although still a fragile one. Clinical benefit has beenachieved over the last 17 years in a limited number of medical conditions for whichpathophysiological studies determined that they were favorable settings. They includeinherited disorders of the immune system, leukodystrophies, possibly hemoglobinopathies,hemophilia B, and retinal dystrophies. Advances in the treatment of B-cell leukemiasand lymphomas have also been achieved. Adva...

  6. Targeting Gene-Virotherapy for Cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-Yuan LIU; Jing-Fa GU; Wen-Fang SHI

    2005-01-01

    Gene therapy and viral therapy for cancer have therapeutic effects, but there has been no significant breakthrough in these two forms of therapy. Therefore, a new strategy called "targeting genevirotherapy", which combines the advantages of gene therapy and viral therapy, has been formulated. This new therapy has stronger antitumor effects than either gene therapy or viral therapy. A tumor-specific replicative adenovirus vector ZD55 (E1B55KD deleted Adv.) was constructed and various single therapeutic genes were inserted into ZD55 to form ZD55-gene. These are the targeting gene-virotherapy genes. But experiments showed that a single gene was not effective in eliminating the tumor mass, and therefore two genes were separately inserted into ZD55. This strategy is called "targeting dual gene-virotherapy" (with PCT patent). Better results were obtained with this strategy, and all the xenograft tumor masses were completely eliminated in all mice when two suitable genes producing a synergetic or compensative effect were chosen. Twenty-six papers on these strategies have been published by researchers in our laboratory.Furthermore, an adenoviral vector with two targeting promoters harboring two antitumor genes has been constructed for cancer therapy. Promising results have been obtained with this adenoviral vectorand another patent has been applied for. This antitumor strategy can be used to kill tumor cells completely with minimum damage to normal cells.

  7. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Gene Therapy and Cell Therapy in the News Position Statements Scientists & Clinicians Job Bank General Grant Information ASGCT Grants and Awards ASGCT ... Password New Investigator Resource Center Join ... American Society of Gene & Cell Therapy is the primary professional membership organization for gene and cell therapy. The Society's members ...

  8. The rat androgen receptor gene promoter

    NARCIS (Netherlands)

    W.M. Baarends (Willy); A.P.N. Themmen (Axel); L.J. Blok (Leen); P. Mackenbach (Petra); A.O. Brinkmann (Albert); D.N. Meijer (Dies); P.W. Faber; J. Trapman (Jan); J.A. Grootegoed (Anton)

    1990-01-01

    markdownabstractAbstract The androgen receptor (AR) is activated upon binding of testosterone or dihydrotestosterone and exerts regulatory effects on gene expression in androgen target cells. To study transcriptional regulation of the rat AR gene itself, the 5' genomic region of this gene was clon

  9. Gene therapy for gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Zhan-Kui Liu

    2003-01-01

    Gastric cancer is common in China, and its early diagnosis and treatment are difficult. In recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. The present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer.

  10. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...

  11. Regulating gene expression : surprises still in store

    NARCIS (Netherlands)

    Jansen, Ritsert C.; Nap, Jan-Peter

    2004-01-01

    Understanding how genes constitute and contribute to the regulatory networks that result in phenotypic diversity is the major challenge of the post-genome era. Recently, it has been shown that major players in gene regulation can be identified by genome-wide linkage analysis of whole-genome gene exp

  12. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Science.gov (United States)

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude

    2016-03-14

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  13. Genes Causing Male Infertility in Humans

    Institute of Scientific and Technical Information of China (English)

    Lawrence C. Layman

    2002-01-01

    There are an accumulating number of identified gene mutations that cause infertility in humans. Most of the known gene mutations impair normal puberty and subsequently cause infertility by either hypothalamic /pituitary deficiency of important tropic factors to the gonad or by gonadal genes.

  14. A constructive approach to gene expression dynamics

    International Nuclear Information System (INIS)

    Recently, experiments on mRNA abundance (gene expression) have revealed that gene expression shows a stationary organization described by a scale-free distribution. Here we propose a constructive approach to gene expression dynamics which restores the scale-free exponent and describes the intermediate state dynamics. This approach requires only one assumption: Markov property

  15. Structure of the murine Thy-1 gene

    NARCIS (Netherlands)

    V. Giguere; K-I. Isobe; F.G. Grosveld (Frank)

    1985-01-01

    textabstractWe have cloned the murine Thy-1.1 (AKR) and Thy-1.2 (Balb/c) genes. The complete exon/intron structure and the nucleotide sequence of the Thy-1.2 gene was determined. The gene contains four exons and three intervening sequences. The complete transcriptional unit gives rise to a tissue an

  16. Uses of antimicrobial genes from microbial genome

    Science.gov (United States)

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  17. The Gene Expression Omnibus Database.

    Science.gov (United States)

    Clough, Emily; Barrett, Tanya

    2016-01-01

    The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome-protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/. PMID:27008011

  18. Horizontal gene transfer in chromalveolates

    Directory of Open Access Journals (Sweden)

    Bhattacharya Debashish

    2007-09-01

    Full Text Available Abstract Background Horizontal gene transfer (HGT, the non-genealogical transfer of genetic material between different organisms, is considered a potentially important mechanism of genome evolution in eukaryotes. Using phylogenomic analyses of expressed sequence tag (EST data generated from a clonal cell line of a free living dinoflagellate alga Karenia brevis, we investigated the impact of HGT on genome evolution in unicellular chromalveolate protists. Results We identified 16 proteins that have originated in chromalveolates through ancient HGTs before the divergence of the genera Karenia and Karlodinium and one protein that was derived through a more recent HGT. Detailed analysis of the phylogeny and distribution of identified proteins demonstrates that eight have resulted from independent HGTs in several eukaryotic lineages. Conclusion Recurring intra- and interdomain gene exchange provides an important source of genetic novelty not only in parasitic taxa as previously demonstrated but as we show here, also in free-living protists. Investigating the tempo and mode of evolution of horizontally transferred genes in protists will therefore advance our understanding of mechanisms of adaptation in eukaryotes.

  19. Revisiting MHC genes in spondyloarthritis.

    Science.gov (United States)

    Breban, Maxime; Costantino, Félicie; André, Claudine; Chiocchia, Gilles; Garchon, Henri-Jean

    2015-06-01

    Spondyloarthritis (SpA) refers to a variety of inflammatory rheumatic disorders with strong heritability. Shared genetic predisposition, as shown by familial aggregation, is largely attributable to the major histocompatibility complex (MHC) locus, which was estimated to account for approximately half of the whole disease heritability. The first predisposing allele identified more than 40 years ago is HLA-B27, which is a major gene predisposing to all forms of SpA. However, despite intensive research, its pathogenesis remains uncertain. Other MHC alleles belonging to the class I and class II regions have been identified to exert additional effect. Candidate-gene approaches and genome-wide studies have recently allowed identification of several new loci residing outside of the MHC region that are involved in the predisposition to SpA. Interestingly, some of those new genes, such as ERAP1, ERAP2, and NPEPPS, code for aminopeptidases that are involved in MHC class I presentation and were shown to interact with HLA-B27. PMID:25903667

  20. The Gene Expression Omnibus database

    Science.gov (United States)

    Clough, Emily; Barrett, Tanya

    2016-01-01

    The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome–protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/. PMID:27008011