Next-Generation Karyotyping Assays for Detecting Inherited Chromosomal Anomalies
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Diagnostic Interpretation of Genetic Studies in Patients with Primary
AAAAI Work Group Report Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma & Immunology Ivan K. Chinn, MD,a,b Alice Y. Chan, MD, PhD,c Karin Chen, MD,d Janet Chou, MD,e,f Morna J. Dorsey, MD, MMSc,c Joud Hajjar, MD, MS,a,b Artemio M. Jongco III, MPH, MD, PhD,g,h,i Michael D. Keller, MD,j Lisa J. Kobrynski, MD, MPH,k Attila Kumanovics, MD,l Monica G. Lawrence, MD,m Jennifer W. Leiding, MD,n,o,p Patricia L. Lugar, MD,q Jordan S. Orange, MD, PhD,r,s Kiran Patel, MD,k Craig D. Platt, MD, PhD,e,f Jennifer M. Puck, MD,c Nikita Raje, MD,t,u Neil Romberg, MD,v,w Maria A. Slack, MD,x,y Kathleen E. Sullivan, MD, PhD,v,w Teresa K. Tarrant, MD,z Troy R. Torgerson, MD, PhD,aa,bb and Jolan E. Walter, MD, PhDn,o,cc Houston, Tex; San Francisco, Calif; Salt Lake City, Utah; Boston, Mass; Great Neck and Rochester, NY; Washington, DC; Atlanta, Ga; Rochester, Minn; Charlottesville, Va; St Petersburg, Fla; Durham, NC; Kansas City, Mo; Philadelphia, Pa; and Seattle, Wash AAAAI Position Statements,Work Group Reports, and Systematic Reviews are not to be considered to reflect current AAAAI standards or policy after five years from the date of publication. The statement below is not to be construed as dictating an exclusive course of action nor is it intended to replace the medical judgment of healthcare professionals. -
Agricultural University of Athens
ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική -
Predicting Human Genes Susceptible to Genomic Instability Associated with Alu/Alu-Mediated Rearrangements
Downloaded from genome.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Predicting human genes susceptible to genomic instability associated with Alu/Alu-mediated rearrangements Key words: genome instability, Alu, genomic rearrangement, MMBIR, bioinformatics, machine- learning Xiaofei Song1, Christine R. Beck1, Renqian Du1, Ian M. Campbell1, Zeynep Coban-Akdemir1, Shen Gu1, Amy M. Breman1,2, Pawel Stankiewicz1,2, Grzegorz Ira1, Chad A. Shaw1,2, James R. Lupski1,3,4,5* 1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 2. Baylor Genetics, Houston, TX 77021, USA 3. Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA 4. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA 5. Texas Children’s Hospital, Houston, TX 77030, USA *Corresponding author: James R. Lupski, M.D., Ph.D., D.Sc. (hon), FAAP, FACMG, FANA, FAAAS, FAAS Cullen Professor, Department of Molecular and Human Genetics and Professor of Pediatrics Member, Human Genome Sequencing Center (HGSC) Baylor College of Medicine One Baylor Plaza Houston, Texas 77030 E-mail: [email protected] Phone: (713) 798-6530 Fax: (713) 798-5073 Downloaded from genome.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract Alu elements, the short interspersed element numbering >1 million copies per human genome, can mediate the formation of copy number variants (CNVs) between substrate pairs. These Alu/Alu-mediated rearrangements (AAMR) can result in pathogenic variants that cause diseases. To investigate the impact of AAMR on gene variation and human health, we first characterized Alus that are involved in mediating CNVs (CNV-Alus) and observed that these Alus tend to be evolutionarily younger. -
The Neurodegenerative Diseases ALS and SMA Are Linked at The
Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gky1093 The neurodegenerative diseases ALS and SMA are linked at the molecular level via the ASC-1 complex Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gky1093/5162471 by [email protected] on 06 November 2018 Binkai Chi, Jeremy D. O’Connell, Alexander D. Iocolano, Jordan A. Coady, Yong Yu, Jaya Gangopadhyay, Steven P. Gygi and Robin Reed* Department of Cell Biology, Harvard Medical School, 240 Longwood Ave. Boston MA 02115, USA Received July 17, 2018; Revised October 16, 2018; Editorial Decision October 18, 2018; Accepted October 19, 2018 ABSTRACT Fused in Sarcoma (FUS) and TAR DNA Binding Protein (TARDBP) (9–13). FUS is one of the three members of Understanding the molecular pathways disrupted in the structurally related FET (FUS, EWSR1 and TAF15) motor neuron diseases is urgently needed. Here, we family of RNA/DNA binding proteins (14). In addition to employed CRISPR knockout (KO) to investigate the the RNA/DNA binding domains, the FET proteins also functions of four ALS-causative RNA/DNA binding contain low-complexity domains, and these domains are proteins (FUS, EWSR1, TAF15 and MATR3) within the thought to be involved in ALS pathogenesis (5,15). In light RNAP II/U1 snRNP machinery. We found that each of of the discovery that mutations in FUS are ALS-causative, these structurally related proteins has distinct roles several groups carried out studies to determine whether the with FUS KO resulting in loss of U1 snRNP and the other two members of the FET family, TATA-Box Bind- SMN complex, EWSR1 KO causing dissociation of ing Protein Associated Factor 15 (TAF15) and EWS RNA the tRNA ligase complex, and TAF15 KO resulting in Binding Protein 1 (EWSR1), have a role in ALS. -
Homo Sapiens, Homo Neanderthalensis and the Denisova Specimen: New Insights on Their Evolutionary Histories Using Whole-Genome Comparisons
Genetics and Molecular Biology, 35, 4 (suppl), 904-911 (2012) Copyright © 2012, Sociedade Brasileira de Genética. Printed in Brazil www.sbg.org.br Research Article Homo sapiens, Homo neanderthalensis and the Denisova specimen: New insights on their evolutionary histories using whole-genome comparisons Vanessa Rodrigues Paixão-Côrtes, Lucas Henrique Viscardi, Francisco Mauro Salzano, Tábita Hünemeier and Maria Cátira Bortolini Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Abstract After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the com- plete genomes of our nearest relative, the chimpanzee (Pan troglodytes), of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A to- tal of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a frac- tion of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence. -
Extensive Cargo Identification Reveals Distinct Biological Roles of the 12 Importin Pathways Makoto Kimura1,*, Yuriko Morinaka1
1 Extensive cargo identification reveals distinct biological roles of the 12 importin pathways 2 3 Makoto Kimura1,*, Yuriko Morinaka1, Kenichiro Imai2,3, Shingo Kose1, Paul Horton2,3, and Naoko 4 Imamoto1,* 5 6 1Cellular Dynamics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan 7 2Artificial Intelligence Research Center, and 3Biotechnology Research Institute for Drug Discovery, 8 National Institute of Advanced Industrial Science and Technology (AIST), AIST Tokyo Waterfront 9 BIO-IT Research Building, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan 10 11 *For correspondence: [email protected] (M.K.); [email protected] (N.I.) 12 13 Editorial correspondence: Naoko Imamoto 14 1 15 Abstract 16 Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of 17 importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple 18 parallel transport pathways that the receptors constitute is poorly understood because only limited 19 numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 20 species of human import receptors with a high-throughput method that employs stable isotope 21 labeling with amino acids in cell culture, an in vitro reconstituted transport system, and quantitative 22 mass spectrometry. The identified cargoes illuminated the manner of cargo allocation to the 23 receptors. The redundancies of the receptors vary widely depending on the cargo protein. Cargoes 24 of the same receptor are functionally related to one another, and the predominant protein groups in 25 the cargo cohorts differ among the receptors. Thus, the receptors are linked to distinct biological 26 processes by the nature of their cargoes. -
Potential Risks of Seismic Surveys to Snow Crab Resources
Environmental Studies Research Fund 220 An Assessment of the Potential Risks of Seismic Surveys to Affect Snow Crab Resources Évaluation des risques potentiels liés aux relevés sismiques sur les ressources de crabe des neiges Canada February 2021 An assessment of the potential risks of seismic surveys to affect Snow Crab resources (ESRF Project 2014-01S) 2 Principal Investigator: Dr. Corey Morris Project sub-component leaders: C. J. Morris1, D. Cote1, B. Martin2, R Saunders-Lee3, M. Rise4, and J. Hanlon1. 1 Science Branch, Fisheries and Oceans Canada P.O. Box 5667, St. John’s, NL, A1C 5X1, 2 JASCO applied sciences division, 3 Fish Food and Allied Workers Union, 4 Department of Ocean Sciences, Memorial University of Newfoundland, 3 The correct citation for this report C. J. Morris, D. Cote, B. Martin, R Saunders-Lee, M. Rise, J. Hanlon., J. Payne, P.M. Regular, D. Mullowney, J. C. Perez-Casanova, M.G. Piersiak, J. Xu, V. Han, D. Kehler, J.R. Hall, S. Lehnert, E. Gonzalez, S. Kumar, I. Bradbury, N. Paddy. 2019. An assessment of the potential risks of seismic surveys to affect Snow Crab resources. St. John’s, NL. 92p. Environmental Studies Research Fund Report No. 220 Disclaimer The Environmental Studies Research Funds are financed from special levies on the oil and gas industry and administered by the Department of Natural Resources for the Minister of Natural Resources Canada and the Minister of Indian Affairs and Northern Development. The Environmental Studies Research Funds and any person acting on their behalf assume no liability arising from the use of the information contained in this document. -
Gene Expression in the Mouse Eye: an Online Resource for Genetics Using 103 Strains of Mice
Molecular Vision 2009; 15:1730-1763 <http://www.molvis.org/molvis/v15/a185> © 2009 Molecular Vision Received 3 September 2008 | Accepted 25 August 2009 | Published 31 August 2009 Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice Eldon E. Geisert,1 Lu Lu,2 Natalie E. Freeman-Anderson,1 Justin P. Templeton,1 Mohamed Nassr,1 Xusheng Wang,2 Weikuan Gu,3 Yan Jiao,3 Robert W. Williams2 (First two authors contributed equally to this work) 1Department of Ophthalmology and Center for Vision Research, Memphis, TN; 2Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, Memphis, TN; 3Department of Orthopedics, University of Tennessee Health Science Center, Memphis, TN Purpose: Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology. Methods: mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts. Results: We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. -
Copy Number Variations in a Cohort of 420 Individuals with Neurodevelopmental Disorders from the South of Brazil
www.nature.com/scientificreports OPEN Copy Number Variations in a Cohort of 420 Individuals with Neurodevelopmental Disorders From the South of Brazil Tiago Fernando Chaves 1,5*, Nathacha Baretto1,5, Luan Freitas de Oliveira1, Maristela Ocampos2, Ingrid Tremel Barbato2, Mayara Anselmi1, Gisele Rozone De Luca3, Jorge Humberto Barbato Filho2, Louise Lapagesse de Camargo Pinto3, Pricila Bernardi4 & Angelica Francesca Maris1* Chromosomal microarray (CMA) is now recommended as frst tier for the evaluation in individuals with unexplained neurodevelopmental disorders (ND). However, in developing countries such as Brazil, classical cytogenetic tests are still the most used in clinical practice, as refected by the scarcity of publications of microarray investigation in larger cohorts. This is a retrospective study which analyses the reading fles of CMA and available clinical data from 420 patients from the south of Brazil, mostly children, with neurodevelopmental disorders requested by medical geneticists and neurologists for diagnostic purpose. Previous karyotyping was reported for 138 and includes 17 with abnormal results. The platforms used for CMA were CYTOSCAN 750K (75%) and CYTOSCAN HD (25%). The sex ratio of the patients was 1.625 males :1 female and the mean age was 9.5 years. A total of 96 pathogenic copy number variations (CNVs), 58 deletions and 38 duplications, were found in 18% of the patients and in all chromosomes, except chromosome 11. For 12% of the patients only variants of uncertain clinical signifcance were found. No clinically relevant CNV was found in 70%. The main referrals for chromosomal microarrays (CMA) were developmental delay (DD), intellectual disability (ID), facial dysmorphism and autism spectrum disorder (ASD). -
Expression Profile of Genes from 12P in Testicular Germ Cell Tumors Of
Oncogene (2003) 22, 1880–1891 & 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00 www.nature.com/onc Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1 S Rodriguez1,7, O Jafer1,7, H Goker1,6, BM Summersgill1, G Zafarana2, AJM Gillis2, RJHLM van Gurp2, JW Oosterhuis2, Y-J Lu1,3, R Huddart4, CS Cooper5, J Clark5, LHJ Looijenga2 and JM Shipley*,1 1Molecular Cytogenetics, Institute of Cancer Research, Sutton, Surrey, UK; 2Pathology/Laboratory for Experimental Patho-Oncology, Erasmus MC University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute 3000 DR Rotterdam, The Netherlands; 3Section of Paediatric Oncology, Institute of Cancer Research, Sutton, Surrey, UK; 4Academic Department of Urology, The Royal Marsden National Health Service Trust and Institute of Cancer Research, Sutton, Surrey, UK; 5Cell Transformation, Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton Surrey, UK Gain of 12p material is invariably associated with Keywords: testicular germ cell tumors of adolescents testicular germ cell tumors (TGCTs) of adolescents and and adults; isochromosome 12p; amplification; micro- adults, most usually as an isochromosome 12p. We array expression profiling; comparative expressed analyzed TGCTs with i(12p) using a global approach to sequence hybridization; candidate genes expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2–p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype Introduction showed higher levels of expression than seminomas. Notably, 12p11.2–p12.1 is amplified in about 10% of Testicular germ cell tumors (TCGTs) of adolescents and TGCTs and CESH analysis of such amplicon cases adults comprise 1% of all malignancies in men and have showed high levels of overexpression from this region. -
Molecular Profiling
HEALTHCARE PROFESSIONALS No. 4 in a series providing the latest information Facts About Molecular Profiling Introduction Cancer therapies have always leveraged the differences between normal and neoplastic cells, and over recent years our understanding of precisely what is different has expanded exponentially. As DNA sequencing technology has uncovered more and more genetic and molecular defects driving blood cancers, therapies have evolved away from “one-size-fits- all” to more targeted approaches, all with a goal of improving clinical outcomes. Molecular profiling helps identify the precise molecular changes associated with malignancy and frequently guides diagnosis, treatment, and prognosis for blood cancers. There are numerous targeted therapies on the market for hematologic malignancies and many more in clinical trials. While advances in genetic analysis have shed welcome light on precise molecular changes driving malignancies, incorporating molecular profiling into routine practice is not without challenges. DNA sequencing reports can deliver overwhelming amounts of difficult-to-interpret information, leaving clinicians uncertain of which mutations are clinically relevant to determine the best course of action. It is challenging to keep pace with the extremely rapid development of newly identified targets or indications for approved therapies. There are access and reimbursement difficulties, particularly for targeted therapies not FDA-approved for a particular malignancy that may harbor a druggable aberration. Finally, patients need to be educated about molecular profiling in order to better inform their decision-making and allow them to be fully engaged partners in their care. This Fact Sheet provides a broad overview of the basics of molecular profiling and how results can inform care for patients with hematologic malignancies. -
Identifying Candidate Genes for 2P15p16.1 Microdeletion Syndrome Using Clinical, Genomic, and Functional Analysis
Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis Hani Bagheri, … , Cheryl Y. Gregory-Evans, Evica Rajcan-Separovic JCI Insight. 2016;1(3):e85461. https://doi.org/10.1172/jci.insight.85461. Research Article Genetics The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34, BCL11A, and REL) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients’ lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients’ LCLs. Other pathways associated with these genes (e.g., NF-κB and Wnt signaling as well as the DNA damage response) were not impaired in patients’ LCLs. Knockdown of xpo1a, rel, bcl11aa, and bcl11ab resulted in abnormal zebrafish