DOCSLIB.ORG

Neurogenetics Made Easy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neurogenetics Made Easy Talk outline • How geneticists can help neuroradiologists • Genetic testing: when, which and why • Genetic testing today Neurogenetics made easy • genome-wide strategies for mutation detection Enza Maria Valente, MD, PhD Dept of Molecular Medicine, University of Pavia • How neuroradiologists can help geneticists Neurogenetics, IRCCS Mondino Foundation • practical examples • the importance of collaboration Whygeneticsisimportant? for patients How geneticists can help improved diagnosis neuroradiologists prognostic indications indications for management and treatment Genetic testing: for families when, which and why assessment of recurrence risks early prenatal diagnosis testing relatives (e.g. carrier testing) new therapies, clinical trials etc… 4 A quick refresh about mendelian inheritance Decision-making flowchart for genetic testing everything that is not acquired (such as infective, toxic, vascular, traumatic Indication to genetic testing etc…) MUST recognize a genetic basis pre-test genetic counselling and informed consent autosomal recessive autosomal dominant two mutated copies of the gene are one mutated copy of a gene is sufficient test selection required to cause the disease to cause the disease healthy heterozygous parents transmit for diseases reducing fitness, the laboratory selection both mutated copies of the gene to mutation usually occurs de novo during 25% offspring parental meiosis Æ sporadic cases GENETIC TESTING horizontal transmission (multiple for diseases non reducing fitness, the affected individuals in one generation) mutation is transmitted vertically from negative or ambiguous results positive results can also present in sporadic cases one affected parent to 50% offspring diagnostic reassessment? implications for management, X-linked further genetic testing? prenatal diagnosis, recessive: hemizygous male patients inherit one mutated copy of a gene on the X research testing? counselling for relatives chrom. from the heterozygous mother (healthy or minimally affected) – also de novo dominant: heterozygous females are affected while in hemizygous males the mutation post-test genetic counselling is lethal or gives rise to much more severe phenotypes – also de novo 5 Indications to diagnostic genetic testing Indications to diagnostic genetic testing validation of diagnostic suspicion (clinical / imaging) diagnosis of conditions without clear clinical or imaging clues prognostic indications (genotype-phenotype correlates) differential diagnosis among distinct conditions with overlapping phenotypes Neurofibromatosis 1 (NF1 gene) café-au-lait spots, axillary freckles Early onset pure cutaneous neurofibromas cerebellar atrophy • AT (ATM) optic gliomas, cranial tumours, other MRI lesions • AOA1 (APTX) • SCA29 (ITPR1) … AT AOA1 ITPR1 Leigh syndrome (mitochondrial) Joubert syndrome onset < 1 year congenital ataxia reproductive risks, carrier testing and prenatal diagnosis severe neurological variable organ involvement specific treatments, therapeutic trials picture typical “molar tooth sign” ++ severe disorders with full penetrance typical basal ganglia NBIA lesions Neuronal Ceroid Lipofuscinoses Lysosomal storage disorders PLAN Infantile NCL Infantile NCL Poretti et al, Neuropediatrics 2015; Vedolin et al, AJNR 2013 Genetic counselling Selection of test genetic testing must be considered an integrated service, mutation(s) already identified in affected family members preceded and followed by specific genetic counseling genetic testing specifically targeted to confirm the familial mutation(s) an appropriately trained person (clinical or medical geneticist, genetic counsellor, or genetic nurse) offers the patient and his family accurate and genetic and molecular homogeneity comprehensive information on: a specific mutation causes most cases of a disease (e.g. Friedreich’s Ataxia Æ GAA expansion in the FXN gene) rationale and procedure of the test standardized genetic testing, high sensitivity inheritance, natural history, and management of the disease implications for the health and reproductive choices of the relatives genetic and/or molecular heterogeneity (commonest!) potential benefits, disadvantages, and consequences for the future health, employment, and insurance prospects of the individual The same disease can be caused by different mutations and different mutational mechanisms involving one or even many genes referral for psychosocial support when indicated ataxia-telangiectasia (ATM, very large gene, many mutations) results, especially when positive, should also be rendered in the Joubert syndrome (>40 genes known to date) context of genetic counselling Genetic strategies: high resolution array standard cytogenetics array studies (CNVs) Genetic testing today genome-wide strategies for Ordered pool of genomic sequences (oligos – CGHarray or SNPs – SNParray), which physical position on the genome is known mutation detection The whole genome is analyzed in a single experiment Resolution depends on the length of DNA probes and the average distance between two adjacent probes on the genome on the same chip you can simultaneously test for: - copy number variations on the whole genome (dels-dups) -regionsof homozygosity by descent 12 Dandy Walker syndrome – chrom. 3q25 deletion Dandy Walker syndrome – chrom. 6p25 deletion - heterozygous point mutations: Axenfeld-Rieder syndrome + mild CVH - small deletions or duplications: CVH – mega cisterna magna -large deletions: nearly all have DWS (but 1 normal!!!) 13 14 Grinberg et al, Nat Genet 2004; Ferraris et al, OJRD 2013 Aldinger et al, Nature Genet 2009 Genetic strategies: next generation sequencing (NGS) Caution in interpretation of NGS results linkage studies bioinformatics high-throughput, cost- and time-effective simultaneous resequencing of mutation Æ permanent change polymorphism Æ variant bothconfusion replaced by large portions of the genome in the nucleotide sequence with frequency >1% assumed as pathogenic assumed as benign Current diagnostic applications: variant • target resequencing of panels of genes or clinical exome Æ hundreds of genes of our choice or about 4000-7000 genes known to cause inherited disorders • mutation screening in clinically and genetically heterogeneous disorders pathogenic likely of uncertain likely benign pathogenic significance (VUS) benign • whole exome sequencing Æ the coding regions of the >20.000 genes in our genome • novel gene identification (even in small families/sporadic) • «fishing» for diagnosis in patients with limited clinical-imaging clues with respect to a condition and inheritance pattern (e.g., c.1521_1523delCTT (p.Phe508del), pathogenic, cystic fibrosis, autosomal recessive). 15 Incidental findings in NGS testing Joubert syndrome (>40 genes) findings that have potential health or reproductive importance discovered in the course of conducting research but beyond the aims of the study sequencing laboratories should actively seek examples: and report pathogenic variants in 56 genes - BRCA1-2: breast / ovarian cancer associated with 24 conditions, all with evidence - LDLR: hypercholesterolemia that early intervention can prevent or - PKP2: arithmogenic cardiomiopathy ameliorate severe adverse medical outcomes Comprehensive pre- and post-test counselling is essential 18 Gene-phenotype correlates Ponto-Cerebellar Hypoplasias: clinical and genetic classification NGS-based screening PCH GENE LOCUS CLINICAL FEATURES MKS1 in 400 JS probands EXOSC3, VRK1 9p13 Onset at birth 2% TMEM216 B9D1 TMEM237 other genes PCH1 1% 1% 1% 6% TSEN54, RARS2 14q32 axonal motor neuropathy CSPP1 INPP5E 2% JS + kidney 2% TSEN54 17q25 Onset at birth, dyskinesias / chorea OFD1 PCH2 TSEN2 3p25 vermis less hypoplastic than hemispheres RPGRIP1L 2% 3% TSEN34 19q13 (dragonfly appearance) -Pure JS KIAA0586 -JS + JATD + OFD 3% Onset at birth, optic atrophy negative PCH3 Not known 7q11-q21 TMEM67 hearing impairement JS + liver 6% 43% CC2D2A PCH4/PCH5 TSEN54 17q25 Fetal onset, severe progression, myoclonus 6% PCH6 RARS2 6q15 Onset at birth, mitochondrial defects Variable AHI1 phenotypes 6% PCH7 TOE1 ambiguous genitalia CEP290 C5orf42 8% 9% PCH8 CHMP1A 16q24 onset at birth Pure JS (++ progressive microcephaly, ID, deafness retinopathy) CASK CASK Xp11 Dragonfly/butterfly, normal CC Cerebello- unspecific clinical features, death by age 10 oculo-renal -Pure JS PCH9 AMPD2 1p13 -OFDVI CC hypoplasia, «8» shape of vermis (axial cut) Slow onset, progressive spasticity/seizures PCH10 CPL1 11q12 Absent or delay speech 20 PCH screening – Italian cohort «Shrunken cerebellum»: non-progressive cerebellar atrophy RARS2 VLDLR PPM2/ATP2B3 2% 2% 18 months • unique inclusion criterion: PCH 2% EXOSC3 9 Mild developmental delay confirmed on neuroimaging 5% 9 Cerebellar Ataxia • 61 probands analyzed TSEN54 neg 16% 39% • 44 genes 9 Normal cognitive development or mild intellectual deficit CASK 9 Clinical improvement in time Males: 34% mosaic loss of function 9 No progression of atrophy at severe missense neuroimaging Males: Females: Males: missense or splice het loss of function hemiz. loss of function several genes involved CASK mutations 6 years DD/ID progressive microcephaly most severe clinical presentation nystagmus variable PCH severe to profound DD seizures (not severe) moderate to severe DD/ID rapidly progressive microcephaly (short stature) very limited language cortical atrophy / hypomielination PMM2 (tremor, hypotonia) seizures, short stature, scoliosis severe intractable seizures (dysmorphism) sensory-neural hearing loss
Load more

Recommended publications
  • MOLECULAR GENETICIST UBC's Centre for Applied Neurogenetics, Within the Faculty of Medicine, Division of Neurology and Departm
    MOLECULAR GENETICIST UBC’s Centre for Applied Neurogenetics, within the Faculty of Medicine, Division of Neurology and Department of Medical Genetics, is seeking a talented and highly motivated Postdoctoral Fellow/Research scientist with a strong background in human genetics. The post- holder will join a multi-discipline team and contribute significantly to identify genetic variability that either causes or contributes to the onset of neurologic and neurodegenerative disease. His/her role will involve working closely with bioinformatician, scientific and medical staff to elucidate the genetic architecture of these diseases (particularly Parkinson’s disease) using state- of-the-art approaches, which range from classical linkage, genome-wide genotyping, through next-generation sequencing, mainly exome and other targeted sequencing experiments (Farrer M. Nat. Rev. Genet. 2006; Farrer M. et al., Nat. Genet. 2008; Vilarino-Guell C. et al., Am. J. Hum. Genet. 2011). Results are used for diagnostic and therapeutic development in partnership with other academic groups and the Pharmaceutical industry (Lewis J. et al., Mol. Neurodegeneration 2008; Melrose H et al., Neurobio Dis. 2010). He/she may also participate in the supervision of interns and graduate students, as well as grant writing. The successful candidate will hold a Ph.D. specializing in human molecular genetics, with an aptitude for molecular biology, statistical genetics and/or bioinformatics. Must have experience with Sanger sequencing, Sequenom, TaqMan and microsatellite genotyping, and strong interest in NGS applied to human disease is desired. He/she will have demonstrated research acumen and have a track record of successful publications, ideally in neurologic and/or neurodegenerative disease. For its beauty and amenities Vancouver is consistently ranked within the top 5 cities to live in the world.
    [Show full text]
  • Genetics and Other Human Modification Technologies: Sensible International Regulation Or a New Kind of Arms Race?
    GENETICS AND OTHER HUMAN MODIFICATION TECHNOLOGIES: SENSIBLE INTERNATIONAL REGULATION OR A NEW KIND OF ARMS RACE? HEARING BEFORE THE SUBCOMMITTEE ON TERRORISM, NONPROLIFERATION, AND TRADE OF THE COMMITTEE ON FOREIGN AFFAIRS HOUSE OF REPRESENTATIVES ONE HUNDRED TENTH CONGRESS SECOND SESSION JUNE 19, 2008 Serial No. 110–201 Printed for the use of the Committee on Foreign Affairs ( Available via the World Wide Web: http://www.foreignaffairs.house.gov/ U.S. GOVERNMENT PRINTING OFFICE 43–068PDF WASHINGTON : 2008 For sale by the Superintendent of Documents, U.S. Government Printing Office Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800 Fax: (202) 512–2104 Mail: Stop IDCC, Washington, DC 20402–0001 COMMITTEE ON FOREIGN AFFAIRS HOWARD L. BERMAN, California, Chairman GARY L. ACKERMAN, New York ILEANA ROS-LEHTINEN, Florida ENI F.H. FALEOMAVAEGA, American CHRISTOPHER H. SMITH, New Jersey Samoa DAN BURTON, Indiana DONALD M. PAYNE, New Jersey ELTON GALLEGLY, California BRAD SHERMAN, California DANA ROHRABACHER, California ROBERT WEXLER, Florida DONALD A. MANZULLO, Illinois ELIOT L. ENGEL, New York EDWARD R. ROYCE, California BILL DELAHUNT, Massachusetts STEVE CHABOT, Ohio GREGORY W. MEEKS, New York THOMAS G. TANCREDO, Colorado DIANE E. WATSON, California RON PAUL, Texas ADAM SMITH, Washington JEFF FLAKE, Arizona RUSS CARNAHAN, Missouri MIKE PENCE, Indiana JOHN S. TANNER, Tennessee JOE WILSON, South Carolina GENE GREEN, Texas JOHN BOOZMAN, Arkansas LYNN C. WOOLSEY, California J. GRESHAM BARRETT, South Carolina SHEILA JACKSON LEE, Texas CONNIE MACK, Florida RUBE´ N HINOJOSA, Texas JEFF FORTENBERRY, Nebraska JOSEPH CROWLEY, New York MICHAEL T. MCCAUL, Texas DAVID WU, Oregon TED POE, Texas BRAD MILLER, North Carolina BOB INGLIS, South Carolina LINDA T.
    [Show full text]
  • The Neurogenetics of Group Behavior in Drosophila Melanogaster Pavan Ramdya1,*, Jonathan Schneider2,* and Joel D
    © 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2017) 220, 35-41 doi:10.1242/jeb.141457 REVIEW The neurogenetics of group behavior in Drosophila melanogaster Pavan Ramdya1,*, Jonathan Schneider2,* and Joel D. Levine2,* ABSTRACT that are ripe for neurobiological investigation: the formation of Organisms rarely act in isolation. Their decisions and movements are social networks and the regulation of collective behavior. often heavily influenced by direct and indirect interactions with conspecifics. For example, we each represent a single node within a Social networks social network of family and friends, and an even larger network of In animal groups, individuals can be drawn toward or away from one strangers. This group membership can affect our opinions and another for a variety of reasons. For example, long-lasting bonds actions. Similarly, when in a crowd, we often coordinate our may exist between family members. On shorter time scales, movements with others like fish in a school, or birds in a flock. individuals may be sexually attracted to one another, or to Contributions of the group to individual behaviors are observed environmental resources such as food patches (Ramos-Fernández across a wide variety of taxa but their biological mechanisms remain et al., 2006). Individuals may also avoid one another because of largely unknown. With the advent of powerful computational tools social or sexual competition, or to maintain a comfortable distance as well as the unparalleled genetic accessibility and surprisingly from their neighbors (Simon et al., 2011). The process of satisfying rich social life of Drosophila melanogaster, researchers now have a these opposing forces gives rise to a dynamic group-level structure unique opportunity to investigate molecular and neuronal called a social network (Kossinets and Watts, 2006).
    [Show full text]
  • Computational Neurogenetics
    Journal of Theoretical and Computational Nanoscience, vol.1 (1) American Scientific Publisher, 2004, in print Computational Neurogenetics ∗ Nikola Kasabov ∗∗ and Lubica Benuskova Knowledge Engineering and Discovery Research Institute School of Information Technology Auckland University of Technology Auckland, New Zealand Address: AUT Technology Park, 581-585 Great South Road, Penrose, Auckland, New Zealand Phone 64 9 917 9506 Fax 64 9 917 9501 Emails: [email protected]; [email protected] WWW: http://www.kedri.info ∗ The author to whom correspondence regarding the manuscript should be directed. 1 Journal of Theoretical and Computational Nanoscience, vol.1 (1) American Scientific Publisher, 2004, in print Abstract The aim of the paper is to introduce the scope and the problems of a new research area called Computational Neurogenetics (CNG), along with some solutions and directions for further research. CNG is concerned with the study and the development of dynamic neuronal models integrated with gene models. This area brings together knowledge from various science disciplines, such as computer and information science, neuroscience and cognitive study, genetics and molecular biology. A computational neurogenetic model is created to model a brain function or a brain disease manifestation, or to be used as a general mathematical model for solving complex scientific and engineering problems. The CNG area goes beyond modelling simple relationship between a single gene and a single neuronal function or a neuronal parameter. It is the interaction between hundreds and thousands of genes in a neuron and their relationship with the functioning of a neuronal ensemble and the brain as a whole (e.g., learning and memory, speech and vision, epilepsy, mental retardation, aging, neural stem cells, etc.).
    [Show full text]
  • Neurochemistry & Metabolic Test Request Form
    5424 Glenridge Drive NE Neurochemistry & Metabolic Atlanta, GA 30342 USA toll-free: 678.225.0222 Test Request Form fax: 678.225.0212 mnglabs.com We gladly accept deliveries Monday-Saturday, excluding holidays CLIA License #11D0703390; CAP License #1441004; State of Georgia License #060-381 Patient Name DOB STAT Testing Now Available For STAT Testing, please see page 4. Metabolic CSF (MET01) Amino Acids (NC04) Neurotransmitter Metabolites (NC07) Sialic Acid [Disorders with Hypomyelination of Unknown Etiology/ (MET07) Lactate (5HIAA, HVA, 3OMD) [Includes Biomarkers for Pyridoxine Responsive Seizures] Sialic Acid Storage Disorders] (MET11) Pyruvate* (NC05) Pyridoxal 5’-phosphate (NC08) Alpha-Aminoadipic (NC01) 5-Methyltetrahydrofolate [Pyridox[am]ine Phosphateoxidase Deficiency + Semialdehyde [Pyridoxine-Responsive Seizures] (NC02) Neopterin [Marker for CNS CNS Pyridoxal 5’-phosphate Deficiency] Immune System Stimulation] (NC09) 4-Hydroxybutyric Acid (NC06) Succinyladenosine [Succinic Semialdehyde Dehydrogenase (NC03) Neopterin/Tetrahydrobiopterin [Adenylosuccinate Lyase Deficiency] Deficiency] (NC10) Glucose [Glucose Transporter Deficiency] Blood & Muscle (MET02) Amino acids (Plasma) (MET08) Lactate (Plasma) (MET23) Creatine & Guanidinoacetate (MET04) Coenzyme Q10 Level (MET09) Phenylalanine Loading (Plasma) (Leukocytes) Assay (Plasma) (MET24) Glucose (Plasma) (MET05) Coenzyme Q10 Level (MET10) Pyruvate* (Blood) (MET29) 3-O-Methyldopa (Plasma) (Muscle) (MET12) Thymidine/Deoxyuridine [Specific Marker for Aromatic L-Amino Analytes (Plasma)
    [Show full text]
  • Epigenetics the Epicenter for Future Anesthesia Research?
    Epigenetics The Epicenter for Future Anesthesia Research? Creed M. Stary, M.D., Ph.D., Hemal H. Patel, Ph.D., David M. Roth, M.D., Ph.D. ONRAD Hal Wadding- approximately 80% of the human C ton (1905–1975), a British genome is indeed associated with embryologist, geneticist, and phi- at least one biochemical func- losopher, proposed the concept tion: regulation of the expression of epigenetics, defined broadly of coding genes.4 These results in as the bridge between an organ- part explain the observation that Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/123/4/743/372860/20151000_0-00008.pdf by guest on 26 September 2021 ism’s inheritable genome and the the majority of RNA species that observable traits of that organism, are generated are not subsequently such as morphology, physiologi- translated to protein5 and demon- cal properties, and behavior.1 For strate that gene regulation is far example, although a majority of more complex than has been tra- a given organism’s cells share an ditionally believed. identical set of chromosomes, The list of noncoding RNAs embryological development has grown from transfer RNAs results in a wide diversity of cell and ribosomal RNAs to include types, each with individualized the discovery of small nucleolar gene expression patterns and func- “miRs are small (19 to 22 RNAs, long noncoding RNAs, tions. In this light, epigenetics is and, the topic of the current generally now defined as the study nucleotides), highly conserved study by Qiao et al., miRs. miRs of gene expression processes that across species, and.… [Their are important posttranscriptional are impacted by the external envi- regulators that interact with ronment and can be passed to suc- binding to target genes] multiple target mRNAs to coor- cessive generations, independently dinately regulate protein expres- of changes in Watson-Crick DNA results in gene silencing or sion.
    [Show full text]
  • Neurogenetics FRIDAY OCTOBER 27, 2017
    Department of Neurology Fall Symposium: Neurogenetics FRIDAY OCTOBER 27, 2017 https://bit.ly/2fNFmBZ Check in begins at 7:30am Damasio Conference Room University of Iowa Hospitals and Clinics Elevator C, Level 7 PROVIDED BY INTENDED AUDIENCE University of Iowa Health Care Department of Neurology Neurologists, Healthcare Providers, Allied Health, Resi- University of Iowa Roy J. and Lucille A. Carver College of Medicine. dents (current and Former), Fellows, & Students GENERAL INFORMATION OBJECTIVES Upon completion of this program the learner should be able to: • Identify neurogenetic disease of the brain, spinal cord, nerve, and muscle • Utilize the current standards of care for managing these disorders • Describe how to diagnose and differentiate these disorders in a rational manner • Discuss the clinical presentation and management of genetic diseases of the brain, spinal cord, nerve and muscle • Explain advances in translational science for these neurogenetic disorders • Review the underlying etiologies for these disorders and approaches to treatment • Evaluate patients and families with neurogenetic conditions Welcome Reception REGISTRATION A welcome reception will be held Thursday Thanks to several sponsors this years October 26th from 7-9 at the Share Wine Lounge hile symposium is free for all attendees. W & Small Bistro at the Sheraton Iowa City Hotel. registration is open until the start of the conference, we encourage early registration to enable us to provide the Parking best possible service. Parking is available in the hospital
    [Show full text]
  • Clinical Exome Sequencing Tip Sheet – Medicare Item Numbers 73358/73359
    Clinical exome sequencing Tip sheet – Medicare item numbers 73358/73359 Glossary Chromosome microarray (CMA or molecular Monogenic conditions (as opposed karyotype): CMA has a Medicare item number to polygenic or multifactorial conditions) are for patients presenting with intellectual caused by variants in a single gene. Variants disability, developmental delay, autism, or at may be inherited (dominant or recessive least two congenital anomalies. CMA is the fashion), or may occur spontaneously (de recommended first line test in these cases as novo) showing no family history. it can exclude a chromosome cause of disease which is unlikely to be detected by Whole exome sequence – sequencing only exome. the protein coding genes (exons). The exome is ~2% of the genome and contains ~85% of Gene panel is a set of genes that are known to disease-causing gene variants. be associated with a phenotype or disorder. They help narrow down the search Whole genome sequence – sequencing the for variants of interest to genes with evidence entire genome (all genes, including coding linking them to particular phenotypes and noncoding regions) Human phenotype ontology (HPO) terms Singleton – Analysis of the child only. describe a phenotypic abnormality using a Trio – analysis of the child and both biological standard nomenclature. Ideally, all clinicians parents. and scientists are using the same terms. Variant - A change in the DNA code that Mendeliome refers to the ~5,000 genes (out of differs from a reference genome. about 20,000 protein coding genes) that are known to be associated with monogenic disease. As variants in new genes are identified with evidence linking them with human disease, they are added to the Mendeliome.
    [Show full text]
  • Questions You May Want to Ask Your Genetics Team
    Q uestions you May Want to Ask Your Child’s Genetics Team Names of Geneticist and Genetic Counselor: ________________________________________ Phone/Contact Information: _____________________________________________________ Appointment Date: ____________________________________________________________ Next Appointment Date: ________________________________________________________ A “genetics team” is made up of a The purpose of a genetic testing or exam is to find out if the cause of your child’s hearing loss is genetic. About sixty clinical geneticist, a genetic counselor, percent of all hearing loss in babies is caused by changes in and other health care professionals. genes. Genes contain the instructions that tell a person’s cells A clinical geneticist is a doctor who how to grow and support the body. Some changes in a gene can cause hearing loss. Hearing loss can also be caused by specializes in diagnosing and caring infections, certain medication, and risks such as prolonged for people with genetic conditions. loud noise in the environment. For many children, the cause of hearing loss may not be known. A genetic counselor is a health care professional who talks with people The genetics team will ask you questions about your child and family. They will do a complete physical exam and may about the risk for genetic conditions recommend that your child and you have a blood test. They and provides counseling and support. may suggest your child see another doctor or specialist to Members of the genetics team work help them better understand the cause of your child’s hearing loss. Knowing the cause may help you and all the professionals together during a genetics exam. who work with your child better plan for his/her future needs.
    [Show full text]
  • Guide to Interpreting Genomic Reports: a Genomics Toolkit
    Guide to Interpreting Genomic Reports: A Genomics Toolkit A guide to genomic test results for non-genetics providers Created by the Practitioner Education Working Group of the Clinical Sequencing Exploratory Research (CSER) Consortium Genomic Report Toolkit Authors Kelly East, MS, CGC, Wendy Chung MD, PhD, Kate Foreman, MS, CGC, Mari Gilmore, MS, CGC, Michele Gornick, PhD, Lucia Hindorff, PhD, Tia Kauffman, MPH, Donna Messersmith , PhD, Cindy Prows, MSN, APRN, CNS, Elena Stoffel, MD, Joon-Ho Yu, MPh, PhD and Sharon Plon, MD, PhD About this resource This resource was created by a team of genomic testing experts. It is designed to help non-geneticist healthcare providers to understand genomic medicine and genome sequencing. The CSER Consortium1 is an NIH-funded group exploring genomic testing in clinical settings. Acknowledgements This work was conducted as part of the Clinical Sequencing Exploratory Research (CSER) Consortium, grants U01 HG006485, U01 HG006485, U01 HG006546, U01 HG006492, UM1 HG007301, UM1 HG007292, UM1 HG006508, U01 HG006487, U01 HG006507, R01 HG006618, and U01 HG007307. Special thanks to Alexandria Wyatt and Hugo O’Campo for graphic design and layout, Jill Pope for technical editing, and the entire CSER Practitioner Education Working Group for their time, energy, and support in developing this resource. Contents 1 Introduction and Overview ................................................................ 3 2 Diagnostic Results Related to Patient Symptoms: Pathogenic and Likely Pathogenic Variants . 8 3 Uncertain Results
    [Show full text]
  • Psychiatric Genetics, Neurogenetics, and Neurodegeneration
    EDITORIAL published: 14 January 2015 doi: 10.3389/fgene.2014.00467 Psychiatric genetics, neurogenetics, and neurodegeneration Berit Kerner* Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA *Correspondence: [email protected] Edited and Reviewed by: Valerie Knopik, Rhode Island Hospital, USA Keywords: risk gene identification, functional genomic variants, social epigenetics, heterogeneity, pleiotropy, amyotrophic lateral sclerosis (ALS), genome-wide association studies (GWAS), environmental exposure Neuropsychiatric disorders are common, complex, and severe observation that variations in the same gene can influence several disorders that affect the core of a person: their emotions, intel- seemingly unrelated phenotypic traits. Heterogeneity describes lect, and ability to self-regulate. Millions of individuals world- the observation that the same disease can be caused by genetic wide suffer from these disorders; nevertheless, the factors that variationinanyoneofanumberofgenes.Theauthorsalsohigh- lead to the manifestation of symptoms are poorly understood. light recent successes in risk gene identification that were brought Neuropsychiatric disorders are characterized by heterogeneity, about with the help of next-generation sequencing in combi- which means that disorders with similar symptoms and disease nation with linkage studies and/or functional studies in small course do not necessarily share the same disease mechanisms or animals and cell cultures. Sequeira et al. explore
    [Show full text]
  • DP-Genome-Editing-EN-Web
    Discussion paper focusing on the scientific relevance of genome editing and on the ethical, legal and societal issues potentially involved ISSUED BY THE ETHICS COUNCIL OF THE MAX PLANCK SOCIETY 1. Introduction and motivation for the discussion paper Christiane Walch-Solimena As an organization dedicated to fundamental research, the intense controversies have emerged around some of its Max Planck Society (MPG) is committed to pursue issues at applications. Thus, first experiments in human embryonic cells the very frontiers of current knowledge and bears a special re- have been performed already since 2015 in China1 intended to sponsibility to critically evaluate novel scientific developments. correct certain disease-causing mutations. These publications Such assessment includes both the scientific potential as well have set off discussions throughout the scientific community as the risks that may be faced if the scientific findings may be and beyond about the ethical and safety implications of this put into practice one day in the future. To this end, the MPG research. An International Summit on Human Genome Editing Ethics Council has been asked to assemble a working group focused on the future of human genome editing and convened to outline and discuss questions arising from a revolutionary by the US National Academy of Medicine, the UK’s Royal Socie- technology that in recent years has opened up unforeseen ty and the Chinese Academy of Sciences in December 2015 opportunities in the manipulation of genes and genomes: the voiced the need for an ongoing global forum. Statements on CRISPR-Cas9 gene editing and genome engineering technolo- ethical and societal questions of genome editing, also cover- gy.
    [Show full text]