DOCSLIB.ORG

Minor Allele Frequencies and Molecular Pathways Differences For

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Minor Allele Frequencies and Molecular Pathways Differences For Journal of Clinical Medicine Article Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project Salvatore D’Antona 1 , Gloria Bertoli 1 , Isabella Castiglioni 2 and Claudia Cava 1,* 1 Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Via F. Cervi 93, 20090 Segrate, Italy; [email protected] (S.D.); [email protected] (G.B.) 2 Department of Physics “Giuseppe Occhialini”, University of Milan-Bicocca Piazza dell’Ateneo Nuovo, 20126 Milan, Italy; [email protected] * Correspondence: [email protected] Abstract: Amyotrophic lateral sclerosis (ALS) is a complex disease with a late onset and is character- ized by the progressive loss of muscular and respiratory functions. Although recent studies have partially elucidated ALS’s mechanisms, many questions remain such as what the most important molecular pathways involved in ALS are and why there is such a large difference in ALS onset among different populations. In this study, we addressed this issue with a bioinformatics approach, using the United Kingdom Biobank (UKBB) and the European 1000 Genomes Project (1KG) in order to analyze the most ALS-representative single nucleotide polymorphisms (SNPs) that differ for minor allele frequency (MAF) between the United Kingdom population and some European populations including Finnish in Finland, Iberian population in Spain, and Tuscans in Italy. We found 84 SNPs Citation: D’Antona, S.; Bertoli, G.; associated with 46 genes that are involved in different pathways including: “Ca2+ activated K+ Castiglioni, I.; Cava, C. Minor Allele channels”, “cGMP effects”, ”Nitric oxide stimulates guanylate cyclase”, “Proton/oligopeptide co- Frequencies and Molecular Pathways transporters”, and “Signaling by MAPK mutants”. In addition, we revealed that 83% of the 84 SNPs Differences for SNPs Associated with can alter transcription factor-motives binding sites of 224 genes implicated in “Regulation of beta-cell Amyotrophic Lateral Sclerosis in development”, “Transcription-al regulation by RUNX3”, “Transcriptional regulation of pluripotent Subjects Participating in the UKBB and 1000 Genomes Project. J. Clin. stem cells”, and “FOXO-mediated transcription of cell death genes”. In conclusion, the genes and Med. 2021, 10, 3394. https:// pathways analyzed could explain the cause of the difference of ALS onset. doi.org/10.3390/jcm10153394 Keywords: ALS; amyotrophic lateral sclerosis; motor neuron degeneration; molecular pathways; Academic Editor: Emmanuel Andrès minor allele frequencies; UKBB; 1000 genomes project; single nucleotide polymorphism; SNP; GWAS Received: 1 June 2021 Accepted: 28 July 2021 Published: 30 July 2021 1. Introduction Amyotrophic lateral sclerosis (ALS) is a complex and chronic disease with the onset of Publisher’s Note: MDPI stays neutral symptoms occurring generally between the ages of 50 and 65 [1–5]. This disease involves with regard to jurisdictional claims in motor neuron degeneration characterized by the progressive loss of upper and lower motor published maps and institutional affil- neurons at the bulbar and spinal levels [6]. This disorder initially results in a gradual loss of iations. muscular function, and it aggravates with muscle atrophy and an inability to breathe and swallow [7]. ALS occurs in two forms: (i) the sporadic form, which is the most common (90–95% of cases) and has no known hereditary component, and (ii) the family-type (5–10% of cases), which has a hereditary component involving altered genes such as C9orf72, FUS, Copyright: © 2021 by the authors. SOD1, TARDBP, and KIF5A [8–12]. Current therapeutic strategies target one or a few altered Licensee MDPI, Basel, Switzerland. molecular pathways, thus having a minimal effect on the course of the disease and on the This article is an open access article life expectancy of ALS patients [13]. Indeed, more than 50% of patients affected by ALS distributed under the terms and do not survive within three years after diagnosis and 20% of the patients survive between conditions of the Creative Commons five and ten years after symptoms onset [14]. Recent population-based motor neuron Attribution (CC BY) license (https:// disease studies show a significant difference in the incidence of ALS between the world creativecommons.org/licenses/by/ 4.0/). (0.6–2.1/100,000 person per year) and Europe (2.1–3.8/100,000 person per year) [15–18] J. Clin. Med. 2021, 10, 3394. https://doi.org/10.3390/jcm10153394 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 17 J. Clin. Med. 2021, 10, 3394 2 of 16 based motor neuron disease studies show a significant difference in the incidence of ALS between the world (0.6–2.1/100,000 person per year) and Europe (2.1–3.8/100,000 person per year) [15–18] and, in particular, these studies show a disease onset discrepancy among and,Scotland in particular, (3.8 per 100,000 these studies person show‐years) a disease [19] and onset the discrepancyrest of Europe among (such Scotland as Italy (3.8(2.8 perper 100,000100,000 person person-years)‐years)) [[18],19] and suggesting the rest that of Europe differences (such in asgenetic Italy and (2.8 environmental per 100,000 person- com‐ years))ponents [ 18are], crucial suggesting in the that onset differences of this pathology. in genetic and environmental components are crucialAlthough in the onset the ofinvolvement this pathology. of mechanisms such as mitochondrial dysfunction and Although the involvement of mechanisms such as mitochondrial dysfunction and oxidative stress and neuroinflammation have been shown in many studies [13], the path‐ oxidative stress and neuroinflammation have been shown in many studies [13], the patho- ogenetic pathways of ALS are still unclear. To date, the greatest challenge is not only to genetic pathways of ALS are still unclear. To date, the greatest challenge is not only to understand the molecular mechanisms underlying the disease but also to comprehend understand the molecular mechanisms underlying the disease but also to comprehend their their role and how they differ among different populations in order to develop more spe‐ role and how they differ among different populations in order to develop more specific cific strategies for the prediction of onset of ALS and better therapies for managing ALS. strategies for the prediction of onset of ALS and better therapies for managing ALS. Since recent genome‐wide associations studies (GWAS) showed that single nucleo‐ Since recent genome-wide associations studies (GWAS) showed that single nucleotide tide polymorphisms (SNPs) have a central role in the inheritance and onset of complex polymorphisms (SNPs) have a central role in the inheritance and onset of complex traits traits and diseases, such as diabetes II and schizophrenia [20], in this study we investi‐ and diseases, such as diabetes II and schizophrenia [20], in this study we investigated in gated in a systematic way the most significant ALS‐related SNPs that differ between the a systematic way the most significant ALS-related SNPs that differ between the United United Kingdom (UK) population and some European populations (including Finnish Kingdom (UK) population and some European populations (including Finnish populations inpopulations Finland, Iberian in Finland, populations Iberian inpopulations Spain, and in Tuscan Spain, populations and Tuscan in populations Italy). We usedin Italy). the UnitedWe used Kingdom the United Biobank Kingdom (UKBB) Biobank and the (UKBB) European and the 1000 European Genome 1000 Project Genome (1KG) forProject the high(1KG) amount for the and high quality amount of and data quality present. of In data addition, present. these In addition, databases these allow databases us to perform allow anus accurateto perform cross-ethnic an accurate GWAS cross study.‐ethnic Indeed, GWAS thestudy. UK Indeed, population the isUK represented population by is UKBBrepre‐ whilesented the by EuropeanUKBB while populations the European are populations represented are by represented the 1KG. Finally, by the we1KG. explored Finally, the we underlyingexplored the genes underlying and pathways genes and that pathways could be that responsible could be ofresponsible the discrepancy of the discrepancy of the ALS onsetof the among ALS onset these among different these populations. different populations. 2. Materials and Methods 2.1. WorkflowWorkflow The computational approach approach of of this this study study consists consists of ofseven seven steps steps that that we webriefly briefly de‐ describescribe in inFigure Figure 1.1 In. In the the first first step, step, we we selected selected the the SNPs SNPs associated associated with with ALS, ALS, based based on on p‐ pvalue-value and and Minor Minor allele allele frequency frequency (MAF), (MAF), using using a acut cut-off‐off of of 0.001 0.001 and and 0.05, 0.05, respectively. respectively. Figure 1. FlowFlow chart chart for for the the selection selection of ofamyotrophic amyotrophic lateral lateral sclerosis sclerosis-related‐related single single nucleotide nucleotide polymorphisms and pathways. polymorphisms and pathways. In the second step, we submitted the SNPs obtained to a genome association tool to execute the clump procedure. It generates a list of SNPs that we used in the third step to obtain the variants information from the 1KG database and to calculate the differences of J. Clin. Med. 2021, 10, 3394 3 of 16 MAFs between the UK and 1KG populations. Thus, in the third step, we selected SNPs with a statistically significant difference of MAFs between UK and 1KG populations. In the fourth step, we performed an SNP enrichment analysis of our statistically significant SNPs. In the fifth step, we calculated the differences of MAF of SNPs-enriched between the UK and 1KG population, selecting the most ALS-related variants. In the step 6.a, we associated the list of SNPs to genes. In step 6.b, we performed an analysis to investigate the transcription-factor motives of binding sites (TF-MBS) altered by our SNPs.
Load more

Recommended publications
  • Tepzz¥ 6Z54za T
    (19) TZZ¥ ZZ_T (11) EP 3 260 540 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 27.12.2017 Bulletin 2017/52 C12N 15/113 (2010.01) A61K 9/127 (2006.01) A61K 31/713 (2006.01) C12Q 1/68 (2006.01) (21) Application number: 17000579.7 (22) Date of filing: 12.11.2011 (84) Designated Contracting States: • Sarma, Kavitha AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Philadelphia, PA 19146 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • Borowsky, Mark PL PT RO RS SE SI SK SM TR Needham, MA 02494 (US) • Ohsumi, Toshiro Kendrick (30) Priority: 12.11.2010 US 412862 P Cambridge, MA 02141 (US) 20.12.2010 US 201061425174 P 28.07.2011 US 201161512754 P (74) Representative: Clegg, Richard Ian et al Mewburn Ellis LLP (62) Document number(s) of the earlier application(s) in City Tower accordance with Art. 76 EPC: 40 Basinghall Street 11840099.3 / 2 638 163 London EC2V 5DE (GB) (71) Applicant: The General Hospital Corporation Remarks: Boston, MA 02114 (US) •Thecomplete document including Reference Tables and the Sequence Listing can be downloaded from (72) Inventors: the EPO website • Lee, Jeannie T •This application was filed on 05-04-2017 as a Boston, MA 02114 (US) divisional application to the application mentioned • Zhao, Jing under INID code 62. San Diego, CA 92122 (US) •Claims filed after the date of receipt of the divisional application (Rule 68(4) EPC). (54) POLYCOMB-ASSOCIATED NON-CODING RNAS (57) This invention relates to long non-coding RNAs (IncRNAs), libraries of those ncRNAs that bind chromatin modifiers, such as Polycomb Repressive Complex 2, inhibitory nucleic acids and methods and compositions for targeting IncRNAs.
    [Show full text]
  • Identification of Tumor-Associated Cassette Exons in Human Cancer
    Valletti et al. Molecular Cancer 2010, 9:230 http://www.molecular-cancer.com/content/9/1/230 RESEARCH Open Access Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation Alessio Valletti1†, Anna Anselmo2†, Marina Mangiulli1, Ilenia Boria1, Flavio Mignone3, Giuseppe Merla4, Vincenzo D’Angelo5, Apollonia Tullo6, Elisabetta Sbisà6, Anna Maria D’Erchia1, Graziano Pesole1,7* Abstract Background: Many evidences report that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies. Results: We present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma. Conclusion: This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma.
    [Show full text]
  • Anti-NFYC Antibody (ARG66549)
    Product datasheet [email protected] ARG66549 Package: 100 μl anti-NFYC antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes NFYC Tested Reactivity Hu, Ms Tested Application IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name NFYC Antigen Species Human Immunogen KLH-conjugated synthetic peptide encompassing a sequence within the N-term region of Human NFYC. Conjugation Un-conjugated Alternate Names HAP5; NF-YC; Nuclear transcription factor Y subunit gamma; Nuclear transcription factor Y subunit C; CBF-C; HSM; CBFC; Transactivator HSM-1/2; CAAT box DNA-binding protein subunit C; H1TF2A Application Instructions Application table Application Dilution IHC-P 1:100 - 1:200 WB 1:500 - 1:1000 Application Note IHC-P: Antigen Retrieval: Heat mediation was performed in Sodium citrate buffer (pH 6.0). * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Calculated Mw 50 kDa Observed Size 50 kDa Properties Form Liquid Purification Affinity purification with immunogen. Buffer 0.42% Potassium phosphate (pH 7.3), 0.87% NaCl, 0.01% Sodium azide and 30% Glycerol. Preservative 0.01% Sodium azide Stabilizer 30% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/2 Note For laboratory research only, not for drug, diagnostic or other use.
    [Show full text]
  • Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
    www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1.
    [Show full text]
  • Chain Gene Induced by GM-CSF Β Receptor Regulation of Human High-Affinity Ige Molecular Mechanisms for Transcriptional
    Molecular Mechanisms for Transcriptional Regulation of Human High-Affinity IgE Receptor β-Chain Gene Induced by GM-CSF This information is current as Kyoko Takahashi, Natsuko Hayashi, Shuichi Kaminogawa of September 23, 2021. and Chisei Ra J Immunol 2006; 177:4605-4611; ; doi: 10.4049/jimmunol.177.7.4605 http://www.jimmunol.org/content/177/7/4605 Downloaded from References This article cites 39 articles, 16 of which you can access for free at: http://www.jimmunol.org/content/177/7/4605.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 23, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Molecular Mechanisms for Transcriptional Regulation of Human High-Affinity IgE Receptor ␤-Chain Gene Induced by GM-CSF1 Kyoko Takahashi,*† Natsuko Hayashi,*‡ Shuichi Kaminogawa,† and Chisei Ra2* The ␤-chain of the high-affinity receptor for IgE (Fc␧RI) plays an important role in regulating activation of Fc␧RI-expressing cells such as mast cells in allergic reactions.
    [Show full text]
  • The Id-Protein Family in Developmental and Cancer-Associated Pathways Cornelia Roschger and Chiara Cabrele*
    Roschger and Cabrele Cell Communication and Signaling (2017) 15:7 DOI 10.1186/s12964-016-0161-y REVIEW Open Access The Id-protein family in developmental and cancer-associated pathways Cornelia Roschger and Chiara Cabrele* Abstract Inhibitors of DNA binding and cell differentiation (Id) proteins are members of the large family of the helix-loop- helix (HLH) transcription factors, but they lack any DNA-binding motif. During development, the Id proteins play a key role in the regulation of cell-cycle progression and cell differentiation by modulating different cell-cycle regulators both by direct and indirect mechanisms. Several Id-protein interacting partners have been identified thus far, which belong to structurally and functionally unrelated families, including, among others, the class I and II bHLH transcription factors, the retinoblastoma protein and related pocket proteins, the paired-box transcription factors, and the S5a subunit of the 26 S proteasome. Although the HLH domain of the Id proteins is involved in most of their protein-protein interaction events, additional motifs located in their N-terminal and C-terminal regions are required for the recognition of diverse protein partners. The ability of the Id proteins to interact with structurally different proteins is likely to arise from their conformational flexibility: indeed, these proteins contain intrinsically disordered regions that, in the case of the HLH region, undergo folding upon self- or heteroassociation. Besides their crucial role for cell-fate determination and cell-cycle progression during development, other important cellular events have been related to the Id-protein expression in a number of pathologies. Dysregulated Id-protein expression has been associated with tumor growth, vascularization, invasiveness, metastasis, chemoresistance and stemness, as well as with various developmental defects and diseases.
    [Show full text]
  • Molecular Analyses of Malignant Pleural Mesothelioma
    Molecular Analyses of Malignant Pleural Mesothelioma Shir Kiong Lo National Heart and Lung Institute Imperial College Dovehouse Street London SW3 6LY A thesis submitted for MD (Res) Faculty of Medicine, Imperial College London 2016 1 Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer that is strongly associated with asbestos exposure. Majority of patients with MPM present with advanced disease and the treatment paradigm mainly involves palliative chemotherapy and best supportive care. The current chemotherapy options are limited and ineffective hence there is an urgent need to improve patient outcomes. This requires better understanding of the genetic alterations driving MPM to improve diagnostic, prognostic and therapeutic strategies. This research aims to gain further insights in the pathogenesis of MPM by exploring the tumour transcriptional and mutational profiles. We compared gene expression profiles of 25 MPM tumours and 5 non-malignant pleura. This revealed differentially expressed genes involved in cell migration, invasion, cell cycle and the immune system that contribute to the malignant phenotype of MPM. We then constructed MPM-associated co-expression networks using weighted gene correlation network analysis to identify clusters of highly correlated genes. These identified three distinct molecular subtypes of MPM associated with genes involved in WNT and TGF-ß signalling pathways. Our results also revealed genes involved in cell cycle control especially the mitotic phase correlated significantly with poor prognosis. Through exome analysis of seven paired tumour/blood and 29 tumour samples, we identified frequent mutations in BAP1 and NF2. Additionally, the mutational profile of MPM is enriched with genes encoding FAK, MAPK and WNT signalling pathways.
    [Show full text]
  • Supplementary Table 2
    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
    [Show full text]
  • Identifying the Risky SNP of Osteoporosis with ID3-PEP Decision Tree Algorithm
    Hindawi Complexity Volume 2017, Article ID 9194801, 8 pages https://doi.org/10.1155/2017/9194801 Research Article Identifying the Risky SNP of Osteoporosis with ID3-PEP Decision Tree Algorithm Jincai Yang,1 Huichao Gu,1 Xingpeng Jiang,1 Qingyang Huang,2 Xiaohua Hu,1 and Xianjun Shen1 1 School of Computer Science, Central China Normal University, Wuhan 430079, China 2School of Life Science, Central China Normal University, Wuhan 430079, China Correspondence should be addressed to Jincai Yang; [email protected] Received 31 March 2017; Revised 26 May 2017; Accepted 8 June 2017; Published 7 August 2017 Academic Editor: Fang-Xiang Wu Copyright © 2017 Jincai Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the past 20 years, much progress has been made on the genetic analysis of osteoporosis. A number of genes and SNPs associated with osteoporosis have been found through GWAS method. In this paper, we intend to identify the suspected risky SNPs of osteoporosis with computational methods based on the known osteoporosis GWAS-associated SNPs. The process includes two steps. Firstly, we decided whether the genes associated with the suspected risky SNPs are associated with osteoporosis by using random walk algorithm on the PPI network of osteoporosis GWAS-associated genes and the genes associated with the suspected risky SNPs. In order to solve the overfitting problem in ID3 decision tree algorithm, we then classified the SNPs with positive results based on their features of position and function through a simplified classification decision tree which was constructed by ID3 decision tree algorithm with PEP (Pessimistic-Error Pruning).
    [Show full text]
  • 523.Full-Text.Pdf
    ANTICANCER RESEARCH 36: 523-532 (2016) Molecular Pathways Mediating Metastases to the Brain via Epithelial-to-Mesenchymal Transition: Genes, Proteins, and Functional Analysis DHRUVE S. JEEVAN1, JARED B. COOPER1, ALEX BRAUN2, RAJ MURALI1 and MEENA JHANWAR-UNIYAL1 Departments of 1Neurosurgery and 2Pathology, New York Medical College, Valhalla, NY, U.S.A. Abstract. Background: Brain metastases are the leading expressed. Moreover, co-expression of the epithelial marker E- cause of morbidity and mortality among patients with cadherin with the mesenchymal marker vimentin was evident, disseminated cancer. The development of metastatic disease suggesting a state of transition. Expression analysis of involves an orderly sequence of steps enabling tumor cells to transcription factor genes in metastatic brain tumor samples migrate from the primary tumor and colonize at secondary demonstrated an alteration in genes associated with locations. In order to achieve this complex metastatic potential, neurogenesis, differentiation, and reprogramming. a cancer cell is believed to undergo a cellular reprogramming Furthermore, tumor cells grown in astrocytic medium displayed process involving the development of a degree of stemness, via increased cell proliferation and enhanced S-phase cell-cycle a proposed process termed epithelial-to-mesenchymal entry. Additionally, chemotactic signaling from the astrocytic transition (EMT). Upon reaching its secondary site, these environment promoted tumor cell migration. Primary tumor reprogrammed cancer stem cells submit to a reversal process cells and astrocytes were also shown to grow amicably designated mesenchymal-to-epithelial transition (MET), together, forming cell-to-cell interactions. Conclusion: These enabling establishment of metastases. Here, we examined the findings suggest that cellular reprogramming via EMT/MET expression of markers of EMT, MET, and stem cells in plays a critical step in the formation of brain metastases, where metastatic brain tumor samples.
    [Show full text]
  • NFYC Polyclonal Antibody
    For Research Use Only NFYC Polyclonal antibody Catalog Number:10129-2-AP 1 Publications www.ptgcn.com Catalog Number: GenBank Accession Number: Recommended Dilutions: Basic Information 10129-2-AP BC005003 WB 1:500-1:2000 Size: GeneID (NCBI): 470 μg/ml 4802 Source: Full Name: Rabbit nuclear transcription factor Y, gamma Isotype: Calculated MW: IgG 37 kDa, 50 kDa Purification Method: Observed MW: Antigen affinity purification 48 kDa Immunogen Catalog Number: AG0140 Applications Tested Applications: Positive Controls: WB,ELISA WB : K-562 cells; Cited Applications: WB Species Specificity: human, mouse, rat Cited Species: mouse NFYC, also named as Nuclear transcription factor Y subunit gamma or Transactivator HSM-1/2, is a 458 amino acid Background Information protein, which belongs to the NFYC/HAP5 subunit family. NFYC localizes in the nucleus and stimulates the transcription of various genes by recognizing and binding to a CCAAT motif in promoters, for example in type 1 collagen, albumin and beta-actin genes. SP1, NFYC and FOXO3, FOXO4 transcription factors are involved in the regulation of STK11 transcription. Notable Publications Author Pubmed ID Journal Application Tong Zan Z 19365404 Cell Res WB Storage: Storage Store at -20ºC. Stable for one year after shipment. Storage Buffer: PBS with 0.02% sodium azide and 50% glycerol pH 7.3. Aliquoting is unnecessary for -20ºC storage For technical support and original validation data for this product please contact: This product is exclusively available under Proteintech T: 4006900926 E: [email protected] W: ptgcn.com Group brand and is not available to purchase from any other manufacturer. Selected Validation Data K-562 cells were subjected to SDS PAGE followed by western blot with 10129-2-AP (NFYC antibody) at dilution of 1:1000 incubated at room temperature for 1.5 hours..
    [Show full text]
  • NFYC Antibody Cat
    NFYC Antibody Cat. No.: 58-221 NFYC Antibody Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human HOMOLOGY: Predicted species reactivity based on immunogen sequence: Bovine, Mouse, Rat This NFYC antibody is generated from rabbits immunized with a KLH conjugated synthetic IMMUNOGEN: peptide between 100-129 amino acids from the N-terminal region of human NFYC. TESTED APPLICATIONS: WB APPLICATIONS: For WB starting dilution is: 1:1000 PREDICTED MOLECULAR 50 kDa WEIGHT: Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated September 29, 2021 1 https://www.prosci-inc.com/nfyc-antibody-58-221.html PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: NFYC Nuclear transcription factor Y subunit gamma, CAAT box DNA-binding protein subunit C, ALTERNATE NAMES: Nuclear transcription factor Y subunit C, NF-YC, Transactivator HSM-1/2, NFYC ACCESSION NO.: Q13952 PROTEIN GI NO.: 20137773 GENE ID: 4802 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References This gene encodes one subunit of a trimeric complex forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoters of a variety of genes. The encoded protein, subunit C, forms a tight dimer with the B subunit, a BACKGROUND: prerequisite for subunit A association.
    [Show full text]