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Haplotypes of CYP1B1 and CCDC57 Genes in an Afro-Caribbean Female
Molecular Biology Reports (2019) 46:3299–3306 https://doi.org/10.1007/s11033-019-04790-y ORIGINAL ARTICLE Haplotypes of CYP1B1 and CCDC57 genes in an Afro‑Caribbean female population with uterine leiomyoma Angela T. Alleyne1 · Virgil S. Bideau1 Received: 13 December 2018 / Accepted: 28 March 2019 / Published online: 13 April 2019 © Springer Nature B.V. 2019 Abstract Uterine leiomyomas (UL) are prevalent benign tumors, especially among women of African ancestry. The disease also has genetic liability and is infuenced by risk factors such as hormones and obesity. This study investigates the haplotypes of the Cytochrome P450 1B1 gene (CYP1B1) related to hormones and coiled-coil domain containing 57 gene (CCDC57) related to obesity in Afro-Caribbean females. Each haplotype was constructed from unphased sequence data using PHASE v.2.1 software and Haploview v.4.2 was used for linkage disequilibrium (LD) studies. There were contrasting LD observed among the single nucleotide polymorphisms of CYP1B1 and CCDC5. Accordingly, the GTA haplotype of CYP1B1 was signifcantly associated with UL risk (P = 0.02) while there was no association between CCDC57 haplotypes and UL (P = 0.2) for the ATG haplotype. As such, our fndings suggest that the Asp449Asp polymorphism and GTA haplotype of CYP1B1 may contribute to UL susceptibility in women of Afro-Caribbean ancestry in this population. Keywords SNP · Fibroids · Haplotyping · Estrogen · Linkage disequilibrium Introduction consistently having a higher risk of UL development than White women [4]. However cumulatively Black women have Globally, 20–25% of women are clinically diagnosed with an earlier onset for diagnosis than White women [2, 10]. -
Selecting Molecular Markers for a Specific Phylogenetic Problem
MOJ Proteomics & Bioinformatics Review Article Open Access Selecting molecular markers for a specific phylogenetic problem Abstract Volume 6 Issue 3 - 2017 In a molecular phylogenetic analysis, different markers may yield contradictory Claudia AM Russo, Bárbara Aguiar, Alexandre topologies for the same diversity group. Therefore, it is important to select suitable markers for a reliable topological estimate. Issues such as length and rate of evolution P Selvatti Department of Genetics, Federal University of Rio de Janeiro, will play a role in the suitability of a particular molecular marker to unfold the Brazil phylogenetic relationships for a given set of taxa. In this review, we provide guidelines that will be useful to newcomers to the field of molecular phylogenetics weighing the Correspondence: Claudia AM Russo, Molecular Biodiversity suitability of molecular markers for a given phylogenetic problem. Laboratory, Department of Genetics, Institute of Biology, Block A, CCS, Federal University of Rio de Janeiro, Fundão Island, Keywords: phylogenetic trees, guideline, suitable genes, phylogenetics Rio de Janeiro, RJ, 21941-590, Brazil, Tel 21 991042148, Fax 21 39386397, Email [email protected] Received: March 14, 2017 | Published: November 03, 2017 Introduction concept that occupies a central position in evolutionary biology.15 Homology is a qualitative term, defined by equivalence of parts due Over the last three decades, the scientific field of molecular to inherited common origin.16–18 biology has experienced remarkable advancements -
PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
An Automated Pipeline for Retrieving Orthologous DNA Sequences from Genbank in R
life Technical Note phylotaR: An Automated Pipeline for Retrieving Orthologous DNA Sequences from GenBank in R Dominic J. Bennett 1,2,* ID , Hannes Hettling 3, Daniele Silvestro 1,2, Alexander Zizka 1,2, Christine D. Bacon 1,2, Søren Faurby 1,2, Rutger A. Vos 3 ID and Alexandre Antonelli 1,2,4,5 ID 1 Gothenburg Global Biodiversity Centre, Box 461, SE-405 30 Gothenburg, Sweden; [email protected] (D.S.); [email protected] (A.Z.); [email protected] (C.D.B.); [email protected] (S.F.); [email protected] (A.A.) 2 Department of Biological and Environmental Sciences, University of Gothenburg, Box 461, SE-405 30 Gothenburg, Sweden 3 Naturalis Biodiversity Center, P.O. Box 9517, 2300 RA Leiden, The Netherlands; [email protected] (H.H.); [email protected] (R.A.V.) 4 Gothenburg Botanical Garden, Carl Skottsbergsgata 22A, SE-413 19 Gothenburg, Sweden 5 Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford St., Cambridge, MA 02138 USA * Correspondence: [email protected] Received: 28 March 2018; Accepted: 1 June 2018; Published: 5 June 2018 Abstract: The exceptional increase in molecular DNA sequence data in open repositories is mirrored by an ever-growing interest among evolutionary biologists to harvest and use those data for phylogenetic inference. Many quality issues, however, are known and the sheer amount and complexity of data available can pose considerable barriers to their usefulness. A key issue in this domain is the high frequency of sequence mislabeling encountered when searching for suitable sequences for phylogenetic analysis. -
00006396 201510000 00004
King’s Research Portal DOI: 10.1097/j.pain.0000000000000200 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Livshits, G., Macgregor, A. J., Gieger, C., Malkin, I., Moayyeri, A., Grallert, H., Emeny, R. T., Spector, T., Kastenmuller, G., & Williams, F. M. K. (2015). An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker. Pain, 156(10), 1845-1851. https://doi.org/10.1097/j.pain.0000000000000200 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. -
Seq2pathway Vignette
seq2pathway Vignette Bin Wang, Xinan Holly Yang, Arjun Kinstlick May 19, 2021 Contents 1 Abstract 1 2 Package Installation 2 3 runseq2pathway 2 4 Two main functions 3 4.1 seq2gene . .3 4.1.1 seq2gene flowchart . .3 4.1.2 runseq2gene inputs/parameters . .5 4.1.3 runseq2gene outputs . .8 4.2 gene2pathway . 10 4.2.1 gene2pathway flowchart . 11 4.2.2 gene2pathway test inputs/parameters . 11 4.2.3 gene2pathway test outputs . 12 5 Examples 13 5.1 ChIP-seq data analysis . 13 5.1.1 Map ChIP-seq enriched peaks to genes using runseq2gene .................... 13 5.1.2 Discover enriched GO terms using gene2pathway_test with gene scores . 15 5.1.3 Discover enriched GO terms using Fisher's Exact test without gene scores . 17 5.1.4 Add description for genes . 20 5.2 RNA-seq data analysis . 20 6 R environment session 23 1 Abstract Seq2pathway is a novel computational tool to analyze functional gene-sets (including signaling pathways) using variable next-generation sequencing data[1]. Integral to this tool are the \seq2gene" and \gene2pathway" components in series that infer a quantitative pathway-level profile for each sample. The seq2gene function assigns phenotype-associated significance of genomic regions to gene-level scores, where the significance could be p-values of SNPs or point mutations, protein-binding affinity, or transcriptional expression level. The seq2gene function has the feasibility to assign non-exon regions to a range of neighboring genes besides the nearest one, thus facilitating the study of functional non-coding elements[2]. Then the gene2pathway summarizes gene-level measurements to pathway-level scores, comparing the quantity of significance for gene members within a pathway with those outside a pathway. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
UC Riverside UC Riverside Previously Published Works
UC Riverside UC Riverside Previously Published Works Title Analysis of the Candida albicans Phosphoproteome. Permalink https://escholarship.org/uc/item/0663w2hr Journal Eukaryotic cell, 14(5) ISSN 1535-9778 Authors Willger, SD Liu, Z Olarte, RA et al. Publication Date 2015-05-01 DOI 10.1128/ec.00011-15 License https://creativecommons.org/licenses/by-nc-sa/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Analysis of the Candida albicans Phosphoproteome S. D. Willger,a Z. Liu,b R. A. Olarte,c M. E. Adamo,d J. E. Stajich,c L. C. Myers,b A. N. Kettenbach,b,d D. A. Hogana Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAa; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAb; Department of Plant Pathology and Microbiology, University of California, Riverside, California, USAc; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USAd Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm forma- tion, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that pro- tein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
Legionella Genus Genome Provide Multiple, Independent Combinations for Replication in Human Cells
Supplemental Material More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells Laura Gomez-Valero1,2, Christophe Rusniok1,2, Danielle Carson3, Sonia Mondino1,2, Ana Elena Pérez-Cobas1,2, Monica Rolando1,2, Shivani Pasricha4, Sandra Reuter5+, Jasmin Demirtas1,2, Johannes Crumbach1,2, Stephane Descorps-Declere6, Elizabeth L. Hartland4,7,8, Sophie Jarraud9, Gordon Dougan5, Gunnar N. Schroeder3,10, Gad Frankel3, and Carmen Buchrieser1,2,* Table S1: Legionella strains analyzed in the present study Table S2: Type IV secretion systems predicted in the genomes analyzed Table S3: Eukaryotic like domains identified in the Legionella proteins analyzed Table S4: Small GTPases domains detected in the genus Legionella as defined in the CDD ncbi domain database Table S5: Eukaryotic like proteins detected in the Legionella genomes analyzed in this study Table S6: Aminoacid identity of the Dot/Icm components in Legionella species with respect to orthologous proteins in L. pneumophila Paris Table S7: Distribution of seventeen highly conserved Dot/Icm secreted substrates Table S8: Comparison of the effector reperotoire among strains of the same Legionella species Table S9. Number of Dot/Icm secreted proteins predicted in each strain analyzed Table S10: Replication capacity of the different Legionella species analyzed in this study and collection of literature data on Legionella replication Table S11: Orthologous table for all genes of the 80 analyzed strains based on PanOCT. The orthologoss where defined with the program PanOCT using the parameters previously indicated in material and methods.) Figure S1: Distribution of the genes predicted to encode for the biosynthesis of flagella among all Legionella species. -
A Shunt Pathway Limits the Caax Processing of Hsp40 Ydj1p and Regulates Ydj1p-Dependent
1 TITLE 2 A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent 3 phenotypes 4 Emily R. Hildebrandt, Michael Cheng, Peng Zhao, June H. Kim, Lance Wells, and Walter K. 5 Schmidt* 6 Department of Biochemistry and Molecular Biology, The University of Georgia, Athens, GA 7 30602, USA 8 *corresponding author: Walter K. Schmidt, 706-583-8241 (phone), 706-542-1738 (fax), 9 [email protected] (email) 10 11 COMPETING INTERESTS: none 12 13 Key words: CaaX, isoprenylation, HSP40, chaperone, thermotolerance 14 15 ABBREVIATIONS 16 polyacrylamide gel electrophoresis (PAGE) 17 sodium dodecyl sulfate (SDS) 18 heat shock protein 40 (Hsp40) 19 20 ABSTRACT 21 The modifications occurring to CaaX proteins have largely been established using few reporter 22 molecules (e.g. Ras, yeast a-factor mating pheromone). These proteins undergo three 23 coordinated COOH-terminal events: isoprenylation of the cysteine, proteolytic removal of aaX, 24 and COOH-terminal methylation. Here, we investigated the coupling of these modifications in 25 the context of the yeast Ydj1p chaperone. We provide genetic, biochemical, and biophysical 26 evidence that the Ydj1p CaaX motif is isoprenylated but not cleaved and carboxylmethylated. 27 Moreover, we demonstrate that Ydj1p-dependent thermotolerance and Ydj1p localization are 28 perturbed when alternative CaaX motifs are transplanted onto Ydj1p. The abnormal 29 phenotypes revert to normal when post-isoprenylation events are genetically interrupted. Our 30 findings indicate that proper Ydj1p function requires an isoprenylatable CaaX motif that is 31 resistant to post-isoprenylation events. These results expand on the complexity of protein 32 isoprenylation and highlight the impact of post-isoprenylation events in regulating the function of 33 Ydj1p and perhaps other CaaX proteins. -
Targeting PH Domain Proteins for Cancer Therapy
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 12-2018 Targeting PH domain proteins for cancer therapy Zhi Tan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Medicinal Chemistry and Pharmaceutics Commons, Neoplasms Commons, and the Pharmacology Commons Recommended Citation Tan, Zhi, "Targeting PH domain proteins for cancer therapy" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 910. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/910 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TARGETING PH DOMAIN PROTEINS FOR CANCER THERAPY by Zhi Tan Approval page APPROVED: _____________________________________________ Advisory Professor, Shuxing Zhang, Ph.D. _____________________________________________