Mouse Nr1i3 Knockout Project (CRISPR/Cas9)
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Role of Tomm40'523 – Apoe Haplotypes in Alzheimer's Disease Etiology
ROLE OF TOMM40’523 – APOE HAPLOTYPES IN ALZHEIMER’S DISEASE ETIOLOGY – FROM CLINICS TO MITOCHONDRIA RÈMY CARDOSO Tese para obtenção do grau de Doutor em EnvelHecimento e Doenças Crónicas Doutoramento em associação entre: Universidade NOVA de Lisboa (Faculdade de Ciências Médicas | NOVA Medical ScHool - FCM|NMS/UNL) Universidade de Coimbra (Faculdade de Medicina - FM/UC) Universidade do MinHo (Escola de Medicina - EMed/UM) Novembro, 2020 ROLE OF TOMM40’523 – APOE HAPLOTYPES IN ALZHEIMER’S DISEASE ETIOLOGY – FROM CLINICS TO MITOCHONDRIA Rèmy Cardoso Professora Doutora Catarina Resende Oliveira, Professora Catedrática Jubilada da FM/UC Professor Doutor Duarte Barral, Professor Associado da FCM|NMS/UNL Tese para obtenção do grau de Doutor em EnvelHecimento e Doenças Crónicas Doutoramento em associação entre: Universidade NOVA de Lisboa (Faculdade de Ciências Médicas | NOVA Medical ScHool - FCM|NMS/UNL) Universidade de Coimbra (Faculdade de Medicina - FM/UC) Universidade do MinHo (Escola de Medicina - EMed/UM) Novembro, 2020 This thesis was conducted at the Center for Neuroscience and Cell Biology (CNC.CIBB) of University of Coimbra and Coimbra University Hospital (CHUC) and was a collaboration of the following laboratories and departments with the supervision of Catarina Resende Oliveira MD, PhD, Full Professor of FM/UC and the co-supervision of Duarte Barral PhD, Associated professor of Nova Medical School, Universidade Nova de Lisboa: • Neurogenetics laboratory (CNC.CIBB) headed by Maria Rosário Almeida PhD • Neurochemistry laboratory (CHUC) -
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 -
Detailed Analysis of Focal Chromosome Arm 1Q
Detailed Analysis of Focal Chromosome Arm 1q and 6p Amplifications in Urothelial Carcinoma Reveals Complex Genomic Events on 1q, and SOX4 as a Possible Auxiliary Target on 6p. Eriksson, Pontus; Aine, Mattias; Sjödahl, Gottfrid; Staaf, Johan; Lindgren, David; Höglund, Mattias Published in: PLoS ONE DOI: 10.1371/journal.pone.0067222 2013 Link to publication Citation for published version (APA): Eriksson, P., Aine, M., Sjödahl, G., Staaf, J., Lindgren, D., & Höglund, M. (2013). Detailed Analysis of Focal Chromosome Arm 1q and 6p Amplifications in Urothelial Carcinoma Reveals Complex Genomic Events on 1q, and SOX4 as a Possible Auxiliary Target on 6p. PLoS ONE, 8(6), [e67222]. https://doi.org/10.1371/journal.pone.0067222 Total number of authors: 6 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public 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 public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
Functional Characterization of the New 8Q21 Asthma Risk Locus
Functional characterization of the new 8q21 Asthma risk locus Cristina M T Vicente B.Sc, M.Sc A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2017 Faculty of Medicine Abstract Genome wide association studies (GWAS) provide a powerful tool to identify genetic variants associated with asthma risk. However, the target genes for many allergy risk variants discovered to date are unknown. In a recent GWAS, Ferreira et al. identified a new association between asthma risk and common variants located on chromosome 8q21. The overarching aim of this thesis was to elucidate the biological mechanisms underlying this association. Specifically, the goals of this study were to identify the gene(s) underlying the observed association and to study their contribution to asthma pathophysiology. Using genetic data from the 1000 Genomes Project, we first identified 118 variants in linkage disequilibrium (LD; r2>0.6) with the sentinel allergy risk SNP (rs7009110) on chromosome 8q21. Of these, 35 were found to overlap one of four Putative Regulatory Elements (PREs) identified in this region in a lymphoblastoid cell line (LCL), based on epigenetic marks measured by the ENCODE project. Results from analysis of gene expression data generated for LCLs (n=373) by the Geuvadis consortium indicated that rs7009110 is associated with the expression of only one nearby gene: PAG1 - located 732 kb away. PAG1 encodes a transmembrane adaptor protein localized to lipid rafts, which is highly expressed in immune cells. Results from chromosome conformation capture (3C) experiments showed that PREs in the region of association physically interacted with the promoter of PAG1. -
High Throughput Computational Mouse Genetic Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.01.278465; this version posted January 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. High Throughput Computational Mouse Genetic Analysis Ahmed Arslan1+, Yuan Guan1+, Zhuoqing Fang1, Xinyu Chen1, Robin Donaldson2&, Wan Zhu, Madeline Ford1, Manhong Wu, Ming Zheng1, David L. Dill2* and Gary Peltz1* 1Department of Anesthesia, Stanford University School of Medicine, Stanford, CA; and 2Department of Computer Science, Stanford University, Stanford, CA +These authors contributed equally to this paper & Current Address: Ecree Durham, NC 27701 *Address correspondence to: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.09.01.278465; this version posted January 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Background: Genetic factors affecting multiple biomedical traits in mice have been identified when GWAS data that measured responses in panels of inbred mouse strains was analyzed using haplotype-based computational genetic mapping (HBCGM). Although this method was previously used to analyze one dataset at a time; but now, a vast amount of mouse phenotypic data is now publicly available, which could lead to many more genetic discoveries. Results: HBCGM and a whole genome SNP map covering 53 inbred strains was used to analyze 8462 publicly available datasets of biomedical responses (1.52M individual datapoints) measured in panels of inbred mouse strains. As proof of concept, causative genetic factors affecting susceptibility for eye, metabolic and infectious diseases were identified when structured automated methods were used to analyze the output. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Integrative Prediction of Gene Expression with Chromatin Accessibility and Conformation Data
bioRxiv preprint doi: https://doi.org/10.1101/704478; this version posted July 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Integrative prediction of gene expression with chromatin accessibility and conformation data Florian Schmidt1;2;3;y, Fabian Kern1;3;4;y, and Marcel H. Schulz1;2;3;5;6;∗ 1High-throughput Genomics & Systems Biology, Cluster of Excellence on Multimodal Computing and Interaction, Saarland Informatics Campus, 66123 Saarbr¨ucken Germany 2Computational Biology & Applied Algorithmics, Max-Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbr¨ucken Germany 3Center for Bioinformatics, Saarland Informatics Campus, 66123 Saarbr¨ucken Germany 4Chair for Clinical Bioinformatics, Saarland Informatics Campus, 66123 Saarbr¨ucken Germany 5Institute of Cardiovascular Regeneration, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main Germany 6German Center for Cardiovascular Research, Partner site Rhein-Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main Germany y These authors contributed equally ∗ Correspondence: [email protected] Abstract Background: Enhancers play a fundamental role in orchestrating cell state and development. Al- though several methods have been developed to identify enhancers, linking them to their target genes is still an open problem. Several theories have been proposed on the functional mechanisms of en- hancers, which triggered the development of various methods to infer promoter enhancer interactions (PEIs). The advancement of high-throughput techniques describing the three-dimensional organisa- tion of the chromatin, paved the way to pinpoint long-range PEIs. -
Alu Elements, Evolution of the Human Brain, and the Spectrum of Neurological Disease
bioRxiv preprint doi: https://doi.org/10.1101/230367; this version posted December 7, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 6 December 2017 2 3 Alu elements, evolution of the human brain, and the spectrum of neurological disease 4 Peter A. Larsen*1,2, Kelsie E. Hunnicutt1, Roxanne J. Larsen3, Anne D. Yoder1,2, and Ann M. 5 Saunders4 6 7 1Department of Biology, Duke University, Durham, NC 27712 8 2Duke Lemur Center, Duke University, Durham, NC 27712 9 3Duke University School of Medicine, Duke University, Durham, NC 27710 10 4Zinfandel Pharmaceuticals, Inc., Research Triangle Park, NC 27709 11 12 Running title: Alu elements and neurological disease 13 14 *Corresponding Author: 15 Peter A. Larsen 16 130 Science Drive, Box 90338 17 Department of Biology 18 Duke University 19 Durham, NC 27708 20 [email protected] 21 22 23 24 25 1 bioRxiv preprint doi: https://doi.org/10.1101/230367; this version posted December 7, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 26 Abstract 27 Alu elements are a highly successful family of primate-specific retrotransposons that have 28 fundamentally shaped primate evolution, including the evolution of our own species. Alus 29 play critical roles in the formation of neurological networks and the epigenetic regulation of 30 biochemical processes throughout the central nervous system (CNS), and thus are 31 hypothesized to have contributed to the origin of human cognition. -
WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C12Q 1/68 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/EP2012/071868 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 5 November 20 12 (05 .11.20 12) NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (25) Filing Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (26) Publication Language: English ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1118985.9 3 November 201 1 (03. 11.201 1) GB kind of regional protection available): ARIPO (BW, GH, 13/339,63 1 29 December 201 1 (29. 12.201 1) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant: DIAGENIC ASA [NO/NO]; Grenseveien 92, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, N-0663 Oslo (NO). -
Figure S1. 17-Mer Distribution in the Yangtze Finless Porpoise Genome
Figure S1. 17-mer distribution in the Yangtze finless porpoise genome. The x-axis is 17-mer depth (X); the y-axis is the number of sequencing reads at that depth. Figure S2. Sequence depth distribution of the assembly data. The x-axis shows the sequencing depth (X) and the y-axis shows the number of bases at a given depth. The results demonstrate that 99% of bases sequencing depth is more than 20. Figure S3. Comparison of gene structure characteristics of Yangtze finless porpoise and other cetaceans. The x-axis represents the length of corresponding genetic element of exon number and the y-axis represents gene density. Figure S4. Phylogeny relationships between the Yangtze finless porpoise and other mammals reconstructed by RAxML with the GTR+G+I model. Table S1. Summary of sequenced reads Raw Reads Qualified Reads1 Total Read Sequence Physical Total Read Sequence Physical Library SRA Data Length Coverage2 Coverage2 Data Length Coverage2 Coverage2 Insert Size (bp) Number (Gb) (bp) (×) (×) (Gb) (bp) (×) (×) 289 58.94 150.00 23.67 22.80 57.84 149.75 23.23 22.41 SRR6923836 462 71.33 150.00 28.65 44.12 70.12 149.74 28.16 43.44 SRR6923837 624 67.47 150.00 27.10 56.36 63.90 149.67 25.66 53.50 SRR6923834 791 57.58 150.00 23.12 60.97 55.39 149.67 22.24 58.78 SRR6923835 4,000 108.73 150.00 43.67 582.22 70.74 150.00 28.41 378.80 SRR6923832 7,000 115.4 150.00 46.35 1,081.39 84.76 150.00 34.04 794.27 SRR6923833 11,000 107.37 150.00 43.12 1,581.08 79.78 150.00 32.04 1,174.81 SRR6923830 18,000 127.46 150.00 51.19 3,071.33 97.75 150.00 39.26 2,355.42 SRR6923831 Total 714.28 - 286.87 6,500.27 580.28 - 233.04 4,881.43 - 1Raw reads in mate-paired libraries were filtered to remove duplicates and reads with low quality and/or adapter contamination, raw reads in paired-end libraries were filtered in the same manner then subjected to k-mer-based correction. -
Multiscale Genomic Analysis of The
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 5-2009 Multiscale Genomic Analysis of the Corticolimbic System: Uncovering the Molecular and Anatomic Substrates of Anxiety-Related Behavior Khyobeni Mozhui University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Mental and Social Health Commons, Nervous System Commons, and the Neurosciences Commons Recommended Citation Mozhui, Khyobeni , "Multiscale Genomic Analysis of the Corticolimbic System: Uncovering the Molecular and Anatomic Substrates of Anxiety-Related Behavior" (2009). Theses and Dissertations (ETD). Paper 180. http://dx.doi.org/10.21007/etd.cghs.2009.0219. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Multiscale Genomic Analysis of the Corticolimbic System: Uncovering the Molecular and Anatomic Substrates of Anxiety-Related Behavior Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Anatomy and Neurobiology Research Advisor Robert W. Williams, Ph.D. Committee John D. Boughter, Ph.D. Eldon E. Geisert, Ph.D. Kristin M. Hamre, Ph.D. Jeffery D. Steketee, Ph.D. DOI 10.21007/etd.cghs.2009.0219 This dissertation is available at UTHSC Digital