DOCSLIB.ORG

2014-Platform-Abstracts.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

American Society of Human Genetics 64th Annual Meeting October 18–22, 2014 San Diego, CA PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Saturday 41 Statistical Methods for Population 5:30pm–6:50pm: Session 2: Plenary Abstracts Based Studies Room 20A #198–#205 Featured Presentation I (4 abstracts) Hall B1 #1–#4 42 Genome Variation and its Impact on Autism and Brain Development Room 20BC #206–#213 Sunday 43 ELSI Issues in Genetics Room 20D #214–#221 1:30pm–3:30pm: Concurrent Platform Session A (12–21): 44 Prenatal, Perinatal, and Reproductive 12 Patterns and Determinants of Genetic Genetics Room 28 #222–#229 Variation: Recombination, Mutation, 45 Advances in Defining the Molecular and Selection Hall B1 Mechanisms of Mendelian Disorders Room 29 #230–#237 #5-#12 13 Genomic Studies of Autism Room 6AB #13–#20 46 Epigenomics of Normal Populations 14 Statistical Methods for Pedigree- and Disease States Room 30 #238–#245 Based Studies Room 6CF #21–#28 15 Prostate Cancer: Expression Tuesday Informing Risk Room 6DE #29–#36 8:00pm–8:25am: 16 Variant Calling: What Makes the 47 Plenary Abstracts Featured Difference? Room 20A #37–#44 Presentation III Hall BI #246 17 New Genes, Incidental Findings and 10:30am–12:30pm:Concurrent Platform Session D (49 – 58): Unexpected Observations Revealed 49 Detailing the Parts List Using by Exome Sequencing Room 20BC #45–#52 Genomic Studies Hall B1 #247–#254 18 Type 2 Diabetes Genetics Room 20D #53–#60 50 Statistical Methods for Multigene, 19 Genomic Methods in Clinical Practice Room 28 #61–#68 Gene Interaction and Pathway 20 Genetics and Mechanisms in Analyses Room 6AB #255–#262 Neurological Disorders Room 29 #69–#76 51 Neurogenetics: From Gene to 21 Developmental Genetics: Mechanism Room 6CF #263–#270 Immunodeficiencies and Autoimmune 52 Contribution of Common and Rare Disorders Room 30 #77–#84 Variation to Obesity-Related Traits Room 6DE #271–#278 53 The Dynamic Genome: Structural Monday and Somatic Variation Room 20A #279–#286 8:00pm–8:25am: 54 Expanding Clinical Phenotypes Room 20BC #287–#294 22 Plenary Abstracts Featured 55 Cancer Susceptibility Genes: Presentation II Hall BI #85 Identification and Implementation Room 20D #295–#302 10:30am–12:30pm: Concurrent Platform Session B (27 – 36): 56 Balanced and Unbalanced 27 Cloudy with a Chance of Big Data Hall B1 #86–#93 Chromosomal Rearrangements Room 28 #303–#310 28 Architecture and Impact of Human 57 Diagnostic Yield of New Genomic Knockout Alleles Room 6AB #94–#101 Technologies Room 29 #311–#318 29 Population Structure, Admixture, and 58 Genetic/Genomic Education and Human History Room 6CF #102–#109 Services Delivery Room 30 #319–#326 30 Neurogenetics: From Gene to 4:30pm–6:30pm: Concurrent Platform Session E (59–68): Mechanism Room 6DE #110–#117 59 We Have the Technology: 31 Cardiovascular Genetics I: Single Next-Generation Genomic Methods Room 6AB #327–#334 Gene Stories Room 20A #118–#125 60 Hereditary Breast-Ovarian Cancer Room 6CF #335–#342 32 Molecular Insights into Mendelian 61 Genomic Studies of Schizophrenia Disorders Room 20BC #126–#133 and Bipolar Disorder Room 6DE #343–#350 33 Genomic Alterations of Tumors Room 20D #134–#141 62 From Association to Function in 34 Metabolic Disorders: New Diagnostics Complex Traits Room 20A #351–#358 and Pathogenic Insights Room 28 #142–#149 63 Therapy for Genetic Disorders Room 20BC #359–#366 35 Looking between the Streetlamps: 64 Exome Sequencing as Standard of Variant Phasing and Imputation Room 29 #150–#157 Care in Clinical Genetics Room 20D #367–#374 36 Chromatin, Gene Regulation and 65 Beyond the Sequence: Genomic Expression Room 30 #158–#165 Regulation and Disease Room 28 #375–#382 4:30pm–6:30pm: Concurrent Platform Session C (37–46): 66 A Clear Vision for Genetic Eye 37 From Bytes To Phenotypes Hall B1 #166–#173 Diseases Room 29 #383–#390 38 Rare Mutations, Well Done Room 6AB #174–#181 67 Autoimmune Genes: Discovery & 39 Cardiovascular Genetics II: Genetic Function Room 30 #391–#398 Discovery and Characterization Room 6CF #182–#189 68 Pharmacogenetics: From Association 40 Genetics of Complex Neuropsychiatric to Action Room 6AB #398–#406 Disorders Room 6DE #190–#197 Copyright © 2014 The American Society of Human Genetics. All rights reserved. X : 52528$PLCV 09-13-14 02:32:35 Layout: 30917X : Start Odd Page 1 ASHG 2014 Abstracts 1 1 2 The UK10K project: rare variants in health and disease. N. Soranzo, Human-specific gene evolution and structural diversity of the chromo- The UK10K Consortium. Wellcome Trust Sanger Institute, Cambridge, some 16p11.2 autism CNV. X. Nuttle1, G. Giannuzzi2, M.H. Duyzend1, United Kingdom. P.H. Sudmant1, O. Penn1, G. Chiatante3, M. Malig1, J. Huddleston1,4, L. Understanding of how genetic variation contributes to human traits and Denman1, L. Harshman1, C. Baker1, A. Raja1,4, K. Penewit1, F. Antonacci3, which genes are involved is still largely incomplete. Rare and low frequency R. Bernier5, A. Reymond2, E.E. Eichler1,4. 1) Department of Genome Sci- genetic variants (defined as minor allele frequency [MAF] <1% and 1-5%, ences, University of Washington School of Medicine, Seattle, WA, USA; 2) respectively) are thought to play a role in common and rare disease, but Center for Integrative Genomics, University of Lausanne, Lausanne, Switz- until recently it has not been possible to assess their contribution systemati- erland; 3) Department of Biology. University of Bari, Bari, Italy; 4) Howard cally. The UK10K project (www.uk10k.org) studies the contribution rare Hughes Medical Institute, Seattle, WA, USA; 5) Department of Psychiatry, and low frequency variation to a wide spectrum of biomedically relevant University of Washington, Seattle, WA, USA. quantitative traits and diseases with different predicted genetic architecture. Recurrent deletions and duplications at 16p11.2 are a major contributor Here we describe the data generated by the different arms of the UK10K to autism and also associate with schizophrenia and extremes of body project, and use it to address empirically important open questions. We mass index and head circumference. These events occur via nonallelic show that the 24 million novel genetic variants identified provide an extensive homologous recombination (NAHR) between directly oriented segmental reference genetic sample for the UK, with fewer than 10% rare variants duplications (BP4 and BP5) ~600 kbp apart. Using whole genome sequenc- shared with other large scale resources. The resulting haplotype panel ing (WGS) data from 2,551 humans, 86 great apes, a Neanderthal, and a boosts accuracy and coverage of imputation of rare variants in GWAS Denisovan, we observed extensive copy number variation in BP4 and BP5 studies. We discuss the value of these data for discovery and interpretation in human populations and identified BOLA2 as a gene duplicated in Homo of variants of clinical importance, including an evaluation of incidental find- sapiens after our divergence from ancient hominins. Performing massively ings that suggests that greater than 5% participants carry rare and potentially parallel and PacBio sequencing of large-insert clones from orangutan and actionable genetic variants. We describe how demographic history influ- chimpanzee, we generated complete sequence over the 16p11.2 locus in ences the observed weak structuring of rare variation in the UK (MAF= these apes and reconstructed its evolutionary history. We find three inver- 0.1-0.3%), and evaluate empirically the potential for confounding due to sions occurred in the human lineage after divergence from orangutan, affect- stratification in association studies of complex traits. We describe the contri- ing > 1 Mbp of sequence, including 45 genes. In concert with these evolution- bution of common, low frequency and rare variants to 61 biomedically impor- ary inversions, > 950 kbp have been added to the region via segmental tant quantitative traits, describing novel alleles associated with adiponectin duplication. Comparative sequence analyses suggest that BOLA2 was part (ADPOQ), lipids (PCSK9, LPL, APOC3|APOA4|APOA1, PCSK7, CETP, of an ~110 kbp segment that duplicated from BP5 to BP4 ~250 kya at the LIPG, LDLR and APOE) and several other traits. We further discuss general time when Homo sapiens emerged as a species. Modern humans carry at characteristics of rare variant associations from the comparative evaluation least one additional copy of BOLA2 (ranging from 3 to 14 diploid copies) in of the allelic architecture of the 61 traits. The data released to the scientific contrast to apes, Neanderthal, and Denisova, where the gene exists as two community includes individual-level genotypic and phenotypic data, a refer- diploid copies. BOLA2 is thought to be involved in cell proliferation or cell ence panel of haplotypes for imputation of rare variants into genome-wide cycle regulation. RT-PCR and RNA-seq suggest BOLA2 is widely expressed, SNP arrays and analysis protocols and summary results for complex trait and expression levels in lymphoblastoid cell lines correlate with copy number associations based on single-marker and rare variant aggregation tests. Our (r = 0.29). Using the same sequencing strategy as above, we completely results inform future whole-genome and whole-exome sequencing based sequenced four distinct human structural haplotypes at 16p11.2 (> 5 Mbp studies seeking to characterize the role of rare genetic variation in predisposi- of sequence). We discover haplotypes where BP4 and BP5 differ by tion to rare and common disease. hundreds of kbp including tandem duplications of BOLA2, leading to likely differences in predisposition to NAHR. Leveraging our high quality human haplotype sequences, we are currently assaying BOLA2 copy number and refining breakpoints in > 125 patients with a 16p11.2 deletion or duplication. Our preliminary data suggest that breakpoints cluster near the Homo sap- iens-specific duplications involving BOLA2. These findings raise the exciting possibility that predisposition to recurrent rearrangements associated with autism is linked to the emergence of novel duplicated genes in the last 250,000 years of our species' evolution.
Recommended publications
  • ERK Phosphorylation of MED14 in Promoter Complexes During Mitogen-Induced Gene Activation by Elk-1 Matthew D

    ERK Phosphorylation of MED14 in Promoter Complexes During Mitogen-Induced Gene Activation by Elk-1 Matthew D

    Published online 17 September 2013 Nucleic Acids Research, 2013, Vol. 41, No. 22 10241–10253 doi:10.1093/nar/gkt837 ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 Matthew D. Galbraith1,2, Janice Saxton1,LiLi1, Samuel J. Shelton1,3, Hongmei Zhang1,4, Joaquin M. Espinosa2 and Peter E. Shaw1,* 1School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK, 2Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA, 3Department of Neurology, Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 90089, USA and 4Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China Received March 22, 2013; Revised August 21, 2013; Accepted August 28, 2013 ABSTRACT INTRODUCTION The ETS domain transcription factor Elk-1 stimu- The specific and temporal co-ordination of gene expres- lates expression of immediate early genes (IEGs) in sion is a fundamental process of cell-based life with response to mitogens. These events require phos- patterns of gene expression controlling proliferation, dif- phorylation of Elk-1 by extracellular signal-regulated ferentiation and cell death. Immediate early gene (IEG) expression has revealed how crucial regulatory events kinase (ERK) and phosphorylation-dependent inter- revolve around the interface between pathway-specific action of Elk-1 with co-activators, including histone transcription factors and components of the transcription acetyltransferases and the Mediator complex. Elk-1 machinery, involving a plethora of protein interactions also recruits ERK to the promoters of its target and modifications (1,2).
  • Mutations in CDK5RAP2 Cause Seckel Syndrome Go¨ Khan Yigit1,2,3,A, Karen E

    Mutations in CDK5RAP2 Cause Seckel Syndrome Go¨ Khan Yigit1,2,3,A, Karen E

    ORIGINAL ARTICLE Mutations in CDK5RAP2 cause Seckel syndrome Go¨ khan Yigit1,2,3,a, Karen E. Brown4,a,Hu¨ lya Kayserili5, Esther Pohl1,2,3, Almuth Caliebe6, Diana Zahnleiter7, Elisabeth Rosser8, Nina Bo¨ gershausen1,2,3, Zehra Oya Uyguner5, Umut Altunoglu5, Gudrun Nu¨ rnberg2,3,9, Peter Nu¨ rnberg2,3,9, Anita Rauch10, Yun Li1,2,3, Christian Thomas Thiel7 & Bernd Wollnik1,2,3 1Institute of Human Genetics, University of Cologne, Cologne, Germany 2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany 3Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany 4Chromosome Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, UK 5Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey 6Institute of Human Genetics, Christian-Albrechts-University of Kiel, Kiel, Germany 7Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany 8Department of Clinical Genetics, Great Ormond Street Hospital for Children, London, WC1N 3EH, UK 9Cologne Center for Genomics, University of Cologne, Cologne, Germany 10Institute of Medical Genetics, University of Zurich, Schwerzenbach-Zurich, Switzerland Keywords Abstract CDK5RAP2, CEP215, microcephaly, primordial dwarfism, Seckel syndrome Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by pre- natal proportionate short stature, severe microcephaly, intellectual disability, and Correspondence characteristic facial features. Here, we describe the novel homozygous splice-site Bernd Wollnik, Center for Molecular mutations c.383+1G>C and c.4005-9A>GinCDK5RAP2 in two consanguineous Medicine Cologne (CMMC) and Institute of families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal pro- Human Genetics, University of Cologne, tein which is known to be essential for centrosomal cohesion and proper spindle Kerpener Str.
  • Establishing the Pathogenicity of Novel Mitochondrial DNA Sequence Variations: a Cell and Molecular Biology Approach

    Establishing the Pathogenicity of Novel Mitochondrial DNA Sequence Variations: a Cell and Molecular Biology Approach

    Mafalda Rita Avó Bacalhau Establishing the Pathogenicity of Novel Mitochondrial DNA Sequence Variations: a Cell and Molecular Biology Approach Tese de doutoramento do Programa de Doutoramento em Ciências da Saúde, ramo de Ciências Biomédicas, orientada pela Professora Doutora Maria Manuela Monteiro Grazina e co-orientada pelo Professor Doutor Henrique Manuel Paixão dos Santos Girão e pela Professora Doutora Lee-Jun C. Wong e apresentada à Faculdade de Medicina da Universidade de Coimbra Julho 2017 Faculty of Medicine Establishing the pathogenicity of novel mitochondrial DNA sequence variations: a cell and molecular biology approach Mafalda Rita Avó Bacalhau Tese de doutoramento do programa em Ciências da Saúde, ramo de Ciências Biomédicas, realizada sob a orientação científica da Professora Doutora Maria Manuela Monteiro Grazina; e co-orientação do Professor Doutor Henrique Manuel Paixão dos Santos Girão e da Professora Doutora Lee-Jun C. Wong, apresentada à Faculdade de Medicina da Universidade de Coimbra. Julho, 2017 Copyright© Mafalda Bacalhau e Manuela Grazina, 2017 Esta cópia da tese é fornecida na condição de que quem a consulta reconhece que os direitos de autor são pertença do autor da tese e do orientador científico e que nenhuma citação ou informação obtida a partir dela pode ser publicada sem a referência apropriada e autorização. This copy of the thesis has been supplied on the condition that anyone who consults it recognizes that its copyright belongs to its author and scientific supervisor and that no quotation from the
  • In Silico Prediction of High-Resolution Hi-C Interaction Matrices

    In Silico Prediction of High-Resolution Hi-C Interaction Matrices

    ARTICLE https://doi.org/10.1038/s41467-019-13423-8 OPEN In silico prediction of high-resolution Hi-C interaction matrices Shilu Zhang1, Deborah Chasman 1, Sara Knaack1 & Sushmita Roy1,2* The three-dimensional (3D) organization of the genome plays an important role in gene regulation bringing distal sequence elements in 3D proximity to genes hundreds of kilobases away. Hi-C is a powerful genome-wide technique to study 3D genome organization. Owing to 1234567890():,; experimental costs, high resolution Hi-C datasets are limited to a few cell lines. Computa- tional prediction of Hi-C counts can offer a scalable and inexpensive approach to examine 3D genome organization across multiple cellular contexts. Here we present HiC-Reg, an approach to predict contact counts from one-dimensional regulatory signals. HiC-Reg pre- dictions identify topologically associating domains and significant interactions that are enri- ched for CCCTC-binding factor (CTCF) bidirectional motifs and interactions identified from complementary sources. CTCF and chromatin marks, especially repressive and elongation marks, are most important for HiC-Reg’s predictive performance. Taken together, HiC-Reg provides a powerful framework to generate high-resolution profiles of contact counts that can be used to study individual locus level interactions and higher-order organizational units of the genome. 1 Wisconsin Institute for Discovery, 330 North Orchard Street, Madison, WI 53715, USA. 2 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53715, USA. *email: [email protected] NATURE COMMUNICATIONS | (2019) 10:5449 | https://doi.org/10.1038/s41467-019-13423-8 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13423-8 he three-dimensional (3D) organization of the genome has Results Temerged as an important component of the gene regulation HiC-Reg for predicting contact count using Random Forests.
  • Mrna-Lncrna Co-Expression Network Analysis Reveals the Role of Lncrnas in Immune Dysfunction During Severe SARS-Cov-2 Infection

    Mrna-Lncrna Co-Expression Network Analysis Reveals the Role of Lncrnas in Immune Dysfunction During Severe SARS-Cov-2 Infection

    viruses Article mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection Sumit Mukherjee 1 , Bodhisattwa Banerjee 2 , David Karasik 2 and Milana Frenkel-Morgenstern 1,* 1 Cancer Genomics and BioComputing of Complex Diseases Lab, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; [email protected] 2 Musculoskeletal Genetics Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; [email protected] (B.B.); [email protected] (D.K.) * Correspondence: [email protected]; Tel.: +972-72-264-4901 Abstract: The recently emerged SARS-CoV-2 virus is responsible for the ongoing COVID-19 pan- demic that has rapidly developed into a global public health threat. Patients severely affected with COVID-19 present distinct clinical features, including acute respiratory disorder, neutrophilia, cy- tokine storm, and sepsis. In addition, multiple pro-inflammatory cytokines are found in the plasma of such patients. Transcriptome sequencing of different specimens obtained from patients suffering from severe episodes of COVID-19 shows dynamics in terms of their immune responses. However, those host factors required for SARS-CoV-2 propagation and the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive. In the present study, we analyzed the mRNA-long non-coding RNA (lncRNA) co-expression network derived from publicly available SARS-CoV-2-infected transcriptome data of human lung epithelial Citation: Mukherjee, S.; Banerjee, B.; cell lines and bronchoalveolar lavage fluid (BALF) from COVID-19 patients. Through co-expression Karasik, D.; Frenkel-Morgenstern, M.
  • Molecular Dynamics and Evolutionary Aspects of the Transition from the Fully Grown Oocyte to Embryo

    Molecular Dynamics and Evolutionary Aspects of the Transition from the Fully Grown Oocyte to Embryo

    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo Alexei V. Evsikov,1,5 Joel H. Graber,1 J. Michael Brockman,1,2 Aleš Hampl,3 Andrea E. Holbrook,1 Priyam Singh,1,2 John J. Eppig,1 Davor Solter,1,4 and Barbara B. Knowles1 1The Jackson Laboratory, Bar Harbor, Maine 04609, USA; 2 Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA; 3Masaryk University Brno and Institute of Experimental Medicine, 625 00 Brno, Czech Republic; 4Max Planck Institute of Immunobiology, 79108 Freiburg, Germany Fully grown oocytes (FGOs) contain all the necessary transcripts to activate molecular pathways underlying the oocyte-to-embryo transition (OET). To elucidate this critical period of development, an extensive survey of the FGO transcriptome was performed by analyzing 19,000 expressed sequence tags of the Mus musculus FGO cDNA library. Expression of 5400 genes and transposable elements is reported. For a majority of genes expressed in mouse FGOs, homologs transcribed in eggs of Xenopus laevis or Ciona intestinalis were found, pinpointing evolutionary conservation of most regulatory cascades underlying the OET in chordates. A large proportion of identified genes belongs to several gene families with oocyte-restricted expression, a likely result of lineage-specific genomic duplications. Gene loss by mutation and expression in female germline of retrotransposed genes specific to M. musculus is documented. These findings indicate rapid diversification of genes involved in female reproduction. Comparison of the FGO and two-cell embryo transcriptomes demarcated the processes important for oogenesis from those involved in OET and identified novel motifs in maternal mRNAs associated with transcript stability.
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    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

    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.
  • Anatomy of the Axon

    Anatomy of the Axon

    Anatomy of the Axon: Dissecting the role of microtubule plus-end tracking proteins in axons of hippocampal neurons ISBN: 978-90-393-7095-7 On the cover: Interpretation of Rembrandt van Rijn’s iconic oil painting The Anatomy Lesson of Dr. Nicolaes Tulp (1632). Instead of a human subject, a neuron is being dissected under the watchful eye of members of the Hoogenraad & Akhmanova labs circa 2018. The doctoral candidate takes on the role of Dr. Nicolaes Tulp. The year in which this thesis is published, 2019, marks the 350th anniversary of Rembrandt’s passing. It is therefore declared Year of Rembrandt. Cover photography: Jasper Landman (Bob & Fzbl Photography) Design and layout: Dieudonnée van de Willige © 2019; CC-BY-NC-ND. Printed in The Netherlands. Anatomy of the Axon: Dissecting the role of microtubule plus-end tracking proteins in axons of hippocampal neurons Anatomie van de Axon: Ontleding van de rol van microtubulus-plus-eind-bindende eiwitten in axonen van hippocampale neuronen (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. H.R.B.M. Kummeling, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op woensdag 22 mei 2019 des middags te 2.30 uur door Dieudonnée van de Willige geboren op 24 oktober 1990 te Antwerpen, België Promotoren: Prof. dr. C.C. Hoogenraad Prof. dr. A. Akhmanova Voor Hans & Miranda Index Preface 7 List of non-standard abbreviations 9 Microtubule plus-end tracking proteins
  • Long Non-Coding RNA EGOT Promotes the Malignant Phenotypes of Hepatocellular Carcinoma Cells and Increases the Expression of HMGA2 Via Down-Regulating Mir-33A-5P

    Long Non-Coding RNA EGOT Promotes the Malignant Phenotypes of Hepatocellular Carcinoma Cells and Increases the Expression of HMGA2 Via Down-Regulating Mir-33A-5P

    OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Long Non-Coding RNA EGOT Promotes the Malignant Phenotypes of Hepatocellular Carcinoma Cells and Increases the Expression of HMGA2 via Down-Regulating miR-33a-5p This article was published in the following Dove Press journal: OncoTargets and Therapy Shimin Wu 1 Background: Chronic hepatitis C virus (HCV) infection is an important risk factor for hepato- Hongwu Ai2 cellular carcinoma (HCC). EGOT is a long non-coding RNA (lncRNA) induced after HCV Kehui Zhang3,4 infection that increases viral replication by antagonizing the antiviral response. Interestingly, Hao Yun3,4 EGOTalso acts as a crucial regulator in multiple cancers. However, its role in HCC remains unclear. Fei Xie3,4 Methods: Real-time PCR (RT-PCR) was used to detect the expression of EGOT in HCC samples and cell lines. CCK-8 assay and colony formation assay were performed to evaluate 1 Center for Clinical Laboratory, General the effect of EGOT on proliferation. Scratch healing assay and transwell assay were used to Hospital of the Yangtze River Shipping, Wuhan Brain Hospital, Wuhan 430030, detect the changes of migration and invasion. Flow cytometry was used to detect the effect of People’s Republic of China; 2Center for EGOT on apoptosis. Interaction between EGOT and miR-33a-5p was determined by bioin- Clinical Laboratory, Wuhan Kangjian formatics analysis, RT-PCR, and dual-luciferase reporter assay. Western blot was used to Maternal and Infant Hospital, Wuhan 430050, People’s Republic of China; confirm that high mobility group protein A2 (HMGA2) could be modulated by EGOT.
  • PAM16 (NM 016069) Human Recombinant Protein Product Data

    PAM16 (NM 016069) Human Recombinant Protein Product Data

    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP302828 PAM16 (NM_016069) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of humanmitochondria-associated protein involved in granulocyte- macrophage colony-stimulating factor signal transduction (Magmas), nuclear gene encoding mitochondrial Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 13.6 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_057153 Locus ID: 51025 UniProt ID: Q9Y3D7 RefSeq Size: 600 Cytogenetics: 16p13.3 RefSeq ORF: 375 Synonyms: CGI-136; MAGMAS; SMDMDM; TIM16; TIMM16 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 PAM16 (NM_016069) Human Recombinant Protein – TP302828 Summary: This gene encodes a mitochondrial protein involved in granulocyte-macrophage colony- stimulating factor (GM-CSF) signaling. This protein also plays a role in the import of nuclear- encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis.
  • Mouse Eif4e3 Knockout Project (CRISPR/Cas9)

    Mouse Eif4e3 Knockout Project (CRISPR/Cas9)

    https://www.alphaknockout.com Mouse Eif4e3 Knockout Project (CRISPR/Cas9) Objective: To create a Eif4e3 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Eif4e3 gene (NCBI Reference Sequence: NM_025829 ; Ensembl: ENSMUSG00000093661 ) is located on Mouse chromosome 6. 7 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 7 (Transcript: ENSMUST00000032151). Exon 3~5 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a knock-out allele exhibit decreased bone trabecula number. Exon 3 starts from about 32.05% of the coding region. Exon 3~5 covers 35.91% of the coding region. The size of effective KO region: ~4602 bp. The KO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 3 4 5 7 Legends Exon of mouse Eif4e3 Knockout region Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 3 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section downstream of Exon 5 is aligned with itself to determine if there are tandem repeats.