Control of Homologous Recombination by the HROB–MCM8–MCM9 Pathway
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Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice
Loyola University Chicago Loyola eCommons Biology: Faculty Publications and Other Works Faculty Publications 2013 Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice Mihaela Palicev Gunter P. Wagner James P. Noonan Benedikt Hallgrimsson James M. Cheverud Loyola University Chicago, [email protected] Follow this and additional works at: https://ecommons.luc.edu/biology_facpubs Part of the Biology Commons Recommended Citation Palicev, M, GP Wagner, JP Noonan, B Hallgrimsson, and JM Cheverud. "Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice." Genome Biology and Evolution 5(10), 2013. This Article is brought to you for free and open access by the Faculty Publications at Loyola eCommons. It has been accepted for inclusion in Biology: Faculty Publications and Other Works by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. © Palicev et al., 2013. GBE Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice Mihaela Pavlicev1,2,*, Gu¨ nter P. Wagner3, James P. Noonan4, Benedikt Hallgrı´msson5,and James M. Cheverud6 1Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria 2Department of Pediatrics, Cincinnati Children‘s Hospital Medical Center, Cincinnati, Ohio 3Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University 4Department of Genetics, Yale University School of Medicine 5Department of Cell Biology and Anatomy, The McCaig Institute for Bone and Joint Health and the Alberta Children’s Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada 6Department of Anatomy and Neurobiology, Washington University *Corresponding author: E-mail: [email protected]. -
Epigenome-Wide Association of Father's Smoking
Environmental Epigenetics, 2019, 1–10 doi: 10.1093/eep/dvz023 Research article RESEARCH ARTICLE Epigenome-wide association of father’s smoking with offspring DNA methylation: a hypothesis-generating study G.T. Mørkve Knudsen1,2,*,†, F.I. Rezwan3,†, A. Johannessen2,4, S.M. Skulstad2, R.J. Bertelsen1, F.G. Real1, S. Krauss-Etschmann5,6, V. Patil7, D. Jarvis8, S.H. Arshad9,10, J.W. Holloway3,‡ and C. Svanes2,4,‡ 1Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway; 2Department of Occupational Medicine, Haukeland University Hospital, N-5021 Bergen, Norway; 3Human Genetics and Genomic Medicine, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; 4Department of Global Public Health and Primary Care, Centre for International Health, University of Bergen, N-5018 Bergen, Norway; 5Division of Experimental Asthma Research, Research Center Borstel, 23845 Borstel, Germany; 6German Center for Lung Research (DZL) and Institute of Experimental Medicine, Christian- Albrechts University of Kiel, 24118 Kiel, Germany; 7David Hide Asthma and Allergy Research Centre, St. Mary’s Hospital, Isle of Wight PO30 5TG, UK; 8Faculty of Medicine, National Heart & Lung Institute, Imperial College, London SW3 6LY, UK; 9Clinical and Experimental Sciences, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; 10NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton SO16 6YD, UK *Correspondence address. Haukanesvegen 260, N-5650 Tysse, Norway; Tel: þ47 977 98 147; E-mail: [email protected] and [email protected] †Equal first authors. ‡Equal last authors. Managing Editor: Moshe Szyf Abstract Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. -
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. -
(TEX) Genes: a Review Focused on Spermatogenesis and Male Fertility
Bellil et al. Basic and Clinical Andrology (2021) 31:9 https://doi.org/10.1186/s12610-021-00127-7 REVIEW ARTICLE Open Access Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility Hela Bellil1, Farah Ghieh2,3, Emeline Hermel2,3, Béatrice Mandon-Pepin2,3 and François Vialard1,2,3* Abstract Spermatogenesis is a complex process regulated by a multitude of genes. The identification and characterization of male-germ-cell-specific genes is crucial to understanding the mechanisms through which the cells develop. The term “TEX gene” was coined by Wang et al. (Nat Genet. 2001; 27: 422–6) after they used cDNA suppression subtractive hybridization (SSH) to identify new transcripts that were present only in purified mouse spermatogonia. TEX (Testis expressed) orthologues have been found in other vertebrates (mammals, birds, and reptiles), invertebrates, and yeasts. To date, 69 TEX genes have been described in different species and different tissues. To evaluate the expression of each TEX/tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database. Various studies have highlighted a role for many of these genes in spermatogenesis. Here, we review current knowledge on the TEX genes and their roles in spermatogenesis and fertilization in humans and, comparatively, in other species (notably the mouse). As expected, TEX genes appear to have a major role in reproduction in general and in spermatogenesis in humans but also in all mammals such as the mouse. Most of them are expressed specifically or predominantly in the testis. -
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). -
Transcriptional Control of Tissue-Resident Memory T Cell Generation
Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2019 © 2019 Filip Cvetkovski All rights reserved ABSTRACT Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells. -
Family-Based Exome Sequencing Identifies Rare Coding Variants in Age-Related Macular Degeneration Rinki Ratnapriya1,2,†,‡,, Ilhan˙ E
Human Molecular Genetics, 2020, Vol. 29, No. 12 2022–2034 doi: 10.1093/hmg/ddaa057 Advance Access Publication Date: 3 April 2020 General Article GENERAL ARTICLE Family-based exome sequencing identifies rare coding variants in age-related macular degeneration Rinki Ratnapriya1,2,†,‡,, Ilhan˙ E. Acar3,†, Maartje J. Geerlings3, Kari Branham4, Alan Kwong5, Nicole T.M. Saksens3, Marc Pauper3, Jordi Corominas3, Madeline Kwicklis1, David Zipprer1, Margaret R. Starostik1, Mohammad Othman4,BeverlyYashar4, Goncalo R. Abecasis5, Emily Y. Chew1, Deborah A. Ferrington6, Carel B. Hoyng3, Anand Swaroop1,‡ and Anneke I. den Hollander3,‡,* 1Neurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA, 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA, 3Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands, 4Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA, 5Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA and 6Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA *To whom correspondence should be addressed at: Department of Ophthalmology, Radboud University Medical Center, Philips van Leydenlaan 15, Route 409, Nijmegen 6525 EX, The Netherlands; Email: [email protected] Abstract Genome-wide association studies (GWAS) have identified 52 independent variants at 34 genetic loci that are associated with age-related macular degeneration (AMD), the most common cause of incurable vision loss in the elderly worldwide. However, causal genes at the majority of these loci remain unknown. In this study, we performed whole exome sequencing of 264 individuals from 63 multiplex families with AMD and analyzed the data for rare protein-altering variants in candidate target genes at AMD-associated loci. -
Transcription Factor ZFP38 Is Essential for Meiosis Prophase I in Male Mice
REPRODUCTIONRESEARCH Transcription factor ZFP38 is essential for meiosis prophase I in male mice Zechen Yan1, Dandan Fan2, Qingjun Meng1, Jinjian Yang1, Wei Zhao1, Fei Guo1, Dongjian Song1, Ruiming Guo1, Ke Sun1 and Jiaxiang Wang1 1Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China and 2Henan Academy of Medical and Pharmaceutical Science, Zhengzhou, Henan, China Correspondence should be addressed to J Wang; Email: [email protected] Abstract The production of haploid gametes by meiosis is a cornerstone of sexual reproduction and maintenance of genome integrity. Zfp38 mRNA is expressed in spermatocytes, indicating that transcription factor ZFP38 has the potential to regulate transcription during meiosis. In this study, we generated Zfp38 conditional knockout mice (Zfp38flox/flox, Stra8-Cre, hereafter called Zfp38 cKO) and found that spermatogenesis did not progress beyond meiosis prophase I in Zfp38 cKO mice. Using a chromosomal spread technique, we observed that Zfp38 cKO spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3 double staining. Progression of DNA double-strand breaks (DSB) repair is disrupted in Zfp38 cKO spermatocytes, as revealed by γ-H2AX, RAD51 and MLH1 staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51, TEX15 and PALB2, were significantly reduced in Zfp38 cKO spermatocytes. Taken together, our data suggest that ZFP38 is critical for the chromosomal synapsis and DSB repairs partially via its regulation of DSB repair- associated protein expression during meiotic progression in mouse. Reproduction (2016) 152 431–437 Introduction recombinases (Pittman et al. -
Associated with Tumorigenesis of Human Astrocytomas (Tumor Suppressor Genes/Antioncogenes/Brain Tumors/Neurofibromatosis/Colon Cancer) M
Proc. Nati. Acad. Sci. USA Vol. 86, pp. 7186-7190, September 1989 Medical Sciences Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas (tumor suppressor genes/antioncogenes/brain tumors/neurofibromatosis/colon cancer) M. EL-AzOUZI*, R. Y. CHUNG*, G. E. FARMER*, R. L. MARTUZA*, P. McL. BLACKt, G. A. ROULEAUt, C. HETTLICH*, E. T. HEDLEY-WHYTE§, N. T. ZERVAS*, K. PANAGOPOULOS*, Y. NAKAMURA¶, J. F. GUSELLAt, AND B. R. SEIZINGER*tII *Molecular Neurooncology Laboratory, Neurosurgery Service, tMolecular Neurogenetics Laboratory, and §Neuropathology Laboratory, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114; *Department of Neurosurgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115; and lHoward Hughes Medical Institute, and University of Utah, Salt Lake City, UT 84132 Communicated by Richard L. Sidman, June 28, 1989 (received for review February 2, 1989) ABSTRACT Astrocytomas, including glioblastoma multi- differentiated astrocytomas and the glioblastoma multiforme. forme, represent the most frequent and deadly primary neo- Although some patients with anaplastic astrocytoma respond plasms of the human nervous system. Despite a number of well to chemotherapy and/or radiotherapy, other patients do previous cytogenetic and oncogene studies primarily focusing not (2). Anaplastic astrocytomas, therefore, may be com- on malignant astrocytomas, the primary mechanism of tumor posed of several distinct biological subgroups, which cannot initiation has remained obscure. The loss or inactivation of be detected by standard histopathological techniques (6, 7). "tumor suppressor" genes are thought to play a fundamental Thus, alternative diagnostic tools, such as genetic markers, role in the development ofmany human cancers. -
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 -
Non-Coding Functional Snps Within the Arthritis-Associated TRAF1-C5 Locus
Non-Coding Functional SNPs Within the Arthritis-Associated TRAF1-C5 Locus The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Chiu, Darren Jianjhih. 2018. Non-Coding Functional SNPs Within the Arthritis-Associated TRAF1-C5 Locus. Master's thesis, Harvard Medical School. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:42076544 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA ! ! Non-coding Functional SNPs within the Arthritis-associated TRAF1-C5 Locus Darren Jianjhih Chiu A Thesis Submitted to the Faculty of The Harvard Medical School in Partial Fulfillment of the Requirements for the Degree of Master of Medical Sciences in Immunology Harvard University Boston, Massachusetts. May, 2018 Thesis Advisor: Dr. Peter Nigrovic Darren Jianjhih Chiu! Non-coding functional SNPs within the arthritis-associated TRAF1-C5 locus Abstract The TRAF1-C5 locus is associated by genome-wide association studies (GWAS) with susceptibility to rheumatoid arthritis and juvenile idiopathic arthritis. Monocytes from healthy individuals with the arthritis-associated risk variant rs3761847 express lower intracellular TRAF1 protein in response to LPS and have greater LPS-induced production of IL-6 and TNF, consistent with a role in inflammatory disease. However, the functional interpretation of this finding remains challenging. Tagging SNPs identified by GWAS are often not causal themselves, but rather simply reside in close association with true functional variants. -
Minichromosome Maintenance Complex Component 8 and 9 Gene Expression in the Menstrual Cycle and Unexplained Primary Ovarian Insufficiency
Journal of Assisted Reproduction and Genetics (2019) 36:57–64 https://doi.org/10.1007/s10815-018-1325-z GENETICS Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency Yelena Dondik1,2 & Zhenmin Lei1 & Jeremy Gaskins1 & Kelly Pagidas1 Received: 2 July 2018 /Accepted: 20 September 2018 /Published online: 1 October 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Purpose DNA repair genes Minichromosome maintenance complex component (MCM) 8 and 9 have been linked with gonadal development, primary ovarian insufficiency (POI), and age at menopause. Our objective was to characterize MCM 8 and 9 gene expression in the menstrual cycle, and to compare MCM 8/9 expression in POI vs normo-ovulatory women. Methods Normo-ovulatory controls (n = 11) and unexplained POI subjects (n = 6) were recruited. Controls provided three blood samples within one menstrual cycle: (1) early follicular phase, (2) ovulation, and (3) mid-luteal phase. Six of 11 controls only provided a follicular phase sample. Amenorrheic POI subjects provided a single, random blood sample. MCM8/9 expression in peripheral blood was assessed with qRTPCR. Analyses were performed using delta-Ct measurements; group differences were transformed to a fold change (FC) and confidence interval (CI). Differences across menstrual cycle phases were compared using random effects ANOVA. Two-sample t tests were used to compare two groups. Results MCM8 expression was significantly lower at ovulation and during the luteal phase, when compared to the follicular phase [FC = 0.69 in the luteal vs follicular phase (p = 0.012, CI = 0.53, 0.90); and 0.65 in the ovulatory vs follicular phase (p = 0.0057, CI = 0.50, 0.85)].