THE HUMAN GENETIC MUTANT CELL REPOSITORY List of Genetic Variants, Chromosomal Aberrations and Normal Cell Cultures Submitted to the Repository Fourth Edition October 1977 I 4^0 162 U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service National Institutes of Health Marine Biological Laboratory Library Woods Hole, Massachusetts Gift of Morton Maser - 1977 — THE HUMAN GENETIC MUTANT CELL REPOSITORY o? x; ^_ 03- 21 i l-=l ! cO j r-q i-q j □ i D : m o D List of Genetic Variants, Chromosomal Aberrations and Normal Cell Cultures Submitted to the Repository Fourth Edition October 1977 INSTITUTE FOR MEDICAL RESEARCH Copewood and Davis Streets Camden, New Jersey 08103 609-966-7377 SPONSORED BY THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES TABLE OF CONTENTS Page PREFACE 1 INTRODUCTION 3 PROCEDURES FOR ORDERING GENETIC MUTANT CULTURES 5 REQUIREMENTS 5 PROCEDURE 5 ADDRESS 5 FEES 6 SHIPPING CHARGES 6 HOW SHIPPED 7 DESCRIPTIVE DATA 7 REQUEST FOR CITATION AND REPRINTS 8 PUBLICATION OF DESCRIPTIVE ARTICLES ON CELL CULTURES STORED IN THE REPOSITORY 8 ASSURANCE FORM 9 AGREEMENT ON LYMPHOID AND VIRUS TRANSFORMED CELLS 10 HUMAN GENETIC MUTANT CELL REPOSITORY MINIMUM SAFETY GUIDELINES RECOMMENDED FOR WORKING WITH LYMPHOID AND VIRUS TRANSFORMED HUMAN CELL LINES 12 SUPERVISION 12 PERSONNEL PRACTICES 13 PHYSICAL CONTROL PRACTICES 14 SUBMISSION OF SPECIMENS TO THE REPOSITORY 16 SUBMISSION SHEET 18 EXPLANATION OF THE CODE FOR RECORDING DATA IN THE COLUMNS OF THE CATALOG 23 HUMAN FIBROBLAST CULTURES WITH BIOCHEMICAL MUTANT CONDITIONS 26 DISORDERS OF AMINO ACID METABOLISM 26 Alkaptonuria 26 Argininemia 26 Argininosuccinicaciduria 26 Citrullinuria (Citrullinemia) 26 Cystinosis 26 Type I - Infantile 26 Type III - Adult 27 Type Unclassified 27 Homocystinuria (Cystathionine Synthase Deficiency) 27 Hyperglycinemia, Non-Ketotic 29 Hypermethioninemia 29 Hyperphenylalanineraia 29 Isovalericacidemia 29 Maple Syrup Urine Disease (Branched-Chain Ketoaciduria) 29 Methylmalonicaciduria 30 Phenylketonuria 30 Propionicacidemia (Hyperglycinemia with Ketoacidosis & Leukopenia) 31 Tyrosinemia 31 Page DISORDERS OF CARBOHYDRATE METABOLISM 31 Amyloidosis 31 Aspartylglycosaminuria 31 Fructose-1 ,6-Diphosphatase Deficiency 31 Fucosidosis 31 Galactosemia (Kinase Deficiency) 32 Galactosemia (Transferase Deficiency) 32 Glucose-6-Phosphate Dehydrogenase Deficiency and Variants 33 Glycogen Storage Diseases 33 Type I - Von Gierke Disease 33 Type II - Pompe Disease 34 Type III - Debranching Enzyme Deficiency 34 Type IV - Andersen Disease 34 Type V - McArdle Disease 34 Type VI - Hers Disease 34 Types VIII, IX - Phosphorylase Kinase Deficiency 34 Hyperpyruvicacidemia 35 Lactic-pyruvic Acidosis 35 Mannosidosis 35 Mucolipidoses 35 Type II - I-Cell Disease 35 Type III - Pseudo-Hurler Polydystrophy 36 Type IV 36 Mucopolysaccharidoses 36 Type IH - Hurler Syndrome 36 Type IH/S - Hurler/Scheie 37 Type IS - Scheie Syndrome 37 Type II - Hunter Syndrome 38 Type IIIA - Sanfilippo Syndrome, A 38 Type IIIB - Sanfilippo Syndrome, B 39 Type IV - Morquio Syndrome 39 Type VI - Maroteaux-Lamy Syndrome 39 Type VII - Beta-Glucuronidase Deficiency 40 Winchester Disease 40 Neuraminidase Deficiency (Acid Sialidase Deficiency) 40 Phosphoglycerate Kinase Deficiency 40 DISORDERS OF LIPID METABOLISM 40 Carnitine Palmitoyl-CoA Transferase Deficiency 40 Ceroid-lipofuscinosis 40 Cholesterol Ester Storage Disease of Liver 40 Fabry Disease (Diffuse Angiokeratoma) 40 Farber Lipogranulomatosis 41 11 Page Gaucher Disease 41 Type 2 - Infantile 41 Type 1 & 3 - Juvenile & Adult 41 GM1 Gangliosidosis - Type I 41 GM2 Gangliosidoses 42 AB Variant 42 Type I - Tay-Sachs Disease 42 Type II - Sandhoff Disease 42 Hyperlipoproteinemia 42 Type II - Familial Hypercholesterolemia 42 Krabbe Disease (Globoid Cell Sclerosis) 43 Metachromatic Leukodystrophy 43 Infantile 43 Adult 44 Multiple Sulfatase Deficiency Disease 44 Niemann-Pick Disease 44 Type A 44 Type B 45 Type C 45 Type Unspecified 45 Refsum Disease 45 Schilder Disease 45 Wolman Disease 45 DISORDERS OF NUCLEOTIDE AND NUCLEIC ACID METABOLISM 45 Adenosine Deaminase Deficiency (Immune Deficiency Disease) 45 Adenosine Phosphoribosyl Transferase Deficiency 46 Inosine Triphosphate Pyrophosphohydrolase (ITPase) Deficiency 46 Lesch-Nyhan Syndrome (HGPRT Deficiency) 46 Orotic Aciduria 47 Xeroderma Pigmentosum 47 Complementation Group A 47 Complementation Group C 47 Complementation Group D 48 Complementation Group E 48 Complementation Group Undetermined 48 OTHER DISORDERS OF KNOWN BIOCHEMISTRY 49 Acatalasia (Acatalasemia) 49 Menkes Syndrome (Kinky Hair Disease) 49 Porphyria 49 Acute Intermittent Porphyria 49 Cutanea Tarda 50 Hereditary Coproporphyria 50 Sickle Cell Anemia (Hemoglobin S) 50 in DISORDERS OF UNCERTAIN BIOCHEMICAL ETIOLOGY Adrenal Hyperplasia (Adrenogenital Syndrome) - Type III Adrenoleukodystrophy (Addison Disease and Cerebral Sclerosis) Agammaglobulinemia, X-Linked Alzheimer Disease of Brain Basal Cell Nevus Syndrome Beckwith-Wiedemann Syndrome ( EMG Syndrome) Campomelic Dwarf Canavan Disease (Spongy Degeneration of the CNS) Cartilage-Hair Hypoplasia (Metaphyseal Chondrodysplasia, McKusick Type) CNS Disorder, Unclassified, Hereditary Chediak-Higashi Syndrome Chondrodystrophy Cockayne Syndrome Conradi Syndrome (Chondrodysplasia Punctata) Corneal Dystrophy, Macular Type Cornelia de Lange Syndrome Cutis Laxa Cystic Fibrosis (Mucoviscidosis) Diabetes Mellitus Dysautonomia (Riley-Day Syndrome) Dyskeratosis Congenita Dystonia Musculorum Deformans Ehler-Danlos Syndrome Type I Type II Type IV Type VI - (Hydroxylysine-Def icient Collagen) Type Unclassified Giant Mitochondrial Disease Gouty Arthritis Huntington Chorea Hypophosphatasia Ichthyosis Congenita Incontinentia Pigmenti Leigh Encephalomyelopathy Lowe Oculocerebrorenal Syndrome Marfan Syndrome Mental Retardation, X-Linked Muscular Dystrophy Becker Type (Progressive Tardive) Duchenne Type (Pseudohypertrophic Progressive) Myositis Ossificans Neurofibromatosis (Von Recklinghausen Disease) Page 51 51 51 51 51 51 51 51 52 52 52 52 52 52 52 52 52 53 53 53 55 55 55 56 56 56 56 56 56 56 56 56 58 58 58 59 59 59 59 59 59 59 59 59 Page Osteogenesis Imperfecta 60 Papular Mucinosis 60 Potter Syndrome (Renal Agenesis) 60 Progeria 60 Retinoblastoma 61 Schizophrenia and Psychiatric Disorders 61 Sea-Blue Histiocyte Disease 61 Spinocerebellar Ataxia 61 Testicular Feminization Syndrome 62 Thanatophoric Dwarfism 62 Tuberous Sclerosis 62 Werdnig-Hof fman Disease 62 Wilson Disease (Hepatolenticular Degeneration) 62 Wiskott-Aldrich Syndrome 62 Zellweger Syndrome 62 HUMAN FIBROBLAST CULTURES WITH CHROMOSOMAL ABERRATIONS 63 SYNDROMES WITH INCREASED CHROMOSOME BREAKAGE 63 Ataxia-Telangiectasia 63 Bloom Syndrome 63 Fanconi Anemia (Pancytopenia) 63 TRANSLOCATIONS 65 Chromosome 1 65 Chromosome 2 67 Chromosome 3 69 Chromosome 4 69 Chromosome 5 71 Chromosome 6 72 Chromosome 7 7 3 Chromosome 8 74 Chromosome 9 75 Chromosome 10 76 Chromosome 11 78 Chromosome 12 78 Chromosome 13 79 Chromosome 14 80 Chromosome 15 81 Chromosome 16 82 Chromosome 17 82 Chromosome 18 84 Chromosome 19 84 Chromosome 20 85 Chromosome 21 85 Chromosome 22 87 Chromosome X 87 Chromosome Y 88 Page INVERSIONS 89 Chromosome 2 89 Chromosome 3 89 Chromosome 4 89 Chromosome 9 89 Chromosome 10 90 Chromosome 13 90 MONOSOMIES 92 Chromosome 21 92 Chromosome X 92 TRISOMY/ POLY SOMY 93 Chromosome 8 93 Chromosome 9 93 Chromosome 10 93 Chromosome 13 93 Chromosome 18 93 Chromosome 21 93 Chromosome 22 94 Chromosome X 94 Chromosome Y 95 TRIPLOIDY 95 DELETION/RING/ ISOCHROMOSOME 95 Chromosome 1 95 Chromosome 2 96 Chromosome 3 96 Chromosome 4 96 Chromosome 5 96 Chromosome 6 96 Chromosome 8 96 Chromosome 9 97 Chromosome 11 97 Chromosome 13 97 Chromosome 16 97 Chromosome 18 97 Chromosome X 98 Chromosome Y 98 TERATOMA 98 GONADAL DYSGENESIS 99 BIOCHEMICAL MARKERS 99 APPARENTLY NORMAL HUMAN FIBROBLAST CELL CULTURES 102 NON-FETAL TISSUE 102 FETAL TISSUE 104 HUMAN AMNIOTIC FLUID CELL CULTURES 105 BIOCHEMICAL MUTANT CONDITIONS 105 Cystinosis 105 VI Page Fabry Disease (Diffuse Angiokeratoma) 105 Galactosemia (Transferase Deficiency) 105 Homocystinuria (Cystathionine Synthase Deficiency) 105 Hunter Syndrome 105 Lesch-Nyhan Syndrome (HGPRT Deficiency) 105 Metachromatic Leukodystrophy 105 CHROMOSOMAL ABERRATIONS 105 Translocation 105 Inversions 106 Trisomy 106 APPARENTLY NORMAL 106 HUMAN LYMPHOCYTE CULTURES WITH BIOCHEMICAL MUTANT CONDITIONS 107 DISORDERS OF AMINO ACID METABOLISM 107 Argininemia 107 Citrullinuria (Citrullinemia) 107 Cystathionuria 107 Homocystinuria (Cystathionine Synthase Deficiency) 108 Maple Syrup Urine Disease (Branched-Chain Ketoaciduria) 108 Phenylketonuria 108 DISORDERS OF CARBOHYDRATE METABOLISM 108 Fucosidosis 108 Galactosemia (Transferase Deficiency) 109 Glycogen Storage Disease 109 Type II - Pompe Disease 109 Mucopolysaccharidosis 109 Type IH - Hurler Syndrome 109 Type IH/S - Hurler/Scheie 109 Type IIIA - Sanfilippo Syndrome, A 109 Type VI - Maroteaux-Lamy Syndrome 109 DISORDERS OF LIPID METABOLISM 109 Abetalipoproteinemia 109 Gaucher Disease 110 Hyperlipidemia 110 Hyperlipoproteinemia 110 Type II - Familial Hypercholesterolemia 110 Metachromatic Leukodystrophy 110 DISORDERS OF NUCLEOTIDE AND NUCLEIC ACID METABOLISM 11 HGPRT Deficiency 11 Inosine Triphosphate Pyrophosphohydrolase (ITPase) Deficiency 1] Lesch-Nyhan Syndrome (HGPRT Deficiency) 11 Xeroderma Pigmentosum 11 OTHER DISORDERS OF KNOWN BIOCHEMISTRY 1] Menkes Syndrome (Kinky Hair Disease) 1. Porphyria 1] Acute Intermittent Porphyria 11 vn Page DISORDERS OF UNCERTAIN BIOCHEMICAL ETIOLOGY 112 Adrenal Hyperplasia (Adrenogenital Syndrome) - Type III 112 Basal Cell Nevus Syndrome 112 Cockayne Syndrome 112 Cystic Fibrosis (Mucoviscidosis) 112 Diabetes Mellitus 113 Dysautonomia (Riley-Day Syndrome) 114 Dyskeratosis Congenita 115 Dystonia Musculorum Deformans 115 Huntington Chorea 115 tfyper IgM 116 Neurofibromatosis (Von Recklinghausen Disease) 117 Persistance of Fetal Hemoglobin (Hemoglobin F) 117 Schizophrenia and Psychiatric Disorders 117 Sea-Blue Histiocyte Disease 118 Tuberous Sclerosis 118 Waldenstrom Macroglobulinemia 118 HUMAN LYMPHOCYTE CULTURES WITH CHROMOSOMAL ABERRATIONS 119 SYNDROME WITH INCREASED CHROMOSOME BREAKAGE 119 Ataxia-Telangiectasia 119 TRANSLOCATIONS 119 TRISOMY/ POLYSOMY 119 UNCLASSIFIED HUMAN LYMPHOCYTE CULTURES 121 Allergic Asthmatic 121 Leukemia 121 Multiple Myeloma 121 APPARENTLY NORMAL HUMAN LYMPHYOCYTE CULTURES 122 SV40 VIRUS TRANSFORMED CELL CULTURES 123 Galactosemia (Transferase Deficiency) 123 Lesch-Nyhan Syndrome (HGPRT Deficiency) 123 Apparently Normal 123 ANIMAL CELL CULTURES 124 Mouse 124 Syrian Baby Hamster 124 Chinese Hamster 125 AGING CELL REPOSITORY CULTURES 126 Alzheimer Disease of Brain 126 Bloom Syndrome 126 Cowden Disease 126 Lowe Oculocerebrorenal Syndrome 126 Mulibrey Nanism 126 Progeria 126 Thanatophoric Dwarfism 127 vixi Page Translocation 127 Xeroderma Pigmentosum 127 TUMOR PATIENTS 127 Chronic Myelogenous Leukemia 127 Glomus Tumor 127 Multiple Myeloma 128 Neuroblastoma 128 Osteogenic Sarcoma 128 Retinoblastoma 128 Wilms Tumor 129 APPARENTLY NORMAL CULTURES 129 SPECIALLY CHARACTERIZED DIPLOID CELL CULTURES 130 APPENDIX A - CODE FOR CULTURE MEDIA 131 APPENDIX B - SUBMITTER CODE 133 APPENDIX C - REPOSITORY PUBLICATIONS IN CYTOGENET. CELL GENET. 153 APPENDIX D - HL-A TYPES 161 APPENDIX E - NSF CELL CULTURE CENTERS 164 INDEX 167 ix Preface to the Fourth Edition Acquisition of cell cultures by the Repository and shipment of cell cultures to investigators both continue to increase at an accelerating rate as shown on the graph which follows this preface. In addition to many new cell cultures and supplementary data on others, the present edition contains new features. McKusick's numbers, where applicable, are inserted immediately following the name of each disease. A bracket is placed around cell cultures from members of a family group. HL-A antigens have been determined on many of the lymphocyte cell cultures and this data is recorded in the table on pages 161-163. Eleven cultures are avail- able from both this Repository and from the American Type Culture Collection in Rockville, Maryland under a different numerical designation. To avoid confusion we have listed the ATCC designation under "Remarks". Camden, N.J., August 1977 Lewis L. Coriell, M.D, Ph.D. Arthur E. Greene, D.Sc. THE HUMAN GENETIC MUTANT CELL REPOSITORY 5,000 4,800 4,600 4,400 4,200 4,000 3,300 3,600 3,400 3,200 3,000 2,800 2,600 2,400 2,200 2,000 1,800 1,600 1,400 1,200 1,000 800 600 400 200 0 Cultures Shipped • Cultures Received •& March 1, 1977 4/73 4/74 4/75 4/76 2/77 I. INTRODUCTION The Human Genetic Mutant Cell Repository established in 1972 by the National Institute of General Medical Sciences at the Institute for Medical Research, Camden, New Jersey, contains low passage skin fibroblast, lymphoblast, amniotic fluid cell, and a few animal cell cultures stored in liquid nitrogen from hereditary diseases includ- ing those with biochemical and chromosome abnormalities and normal controls. Cell cultures stored in the Repository are verified for freedom from contamination, species of origin, karyotype, viability and expression of the biochemical or chromosomal defect. These cells are available to organizations or individuals engaged in health- related research or health delivery concerning early diagnosis, prevention, treatment, counseling and research for control of some of the 2,000 or more inherited diseases that afflict human beings. The problems in many of these diseases are gene abnormalities which alter one or more chemical steps in the normal metabolic sequence of cells. The application of techniques for detailed study of these cellular chemical processes in cell culture is leading to a wealth of information about human genetics and improvement in the prevention and treatment of genetic diseases and probably many other diseases in which genetic factors are not yet recognized to play a significant role. The Repository program has been developed by the National Institute of General Medical Sciences with the help of a scientific advisory committee which periodically reviews the progress of the collection and provides advice on the acquisition of cell lines. Cell cultures are listed alphabetically under cell type and biochemical or morphological abnormalities including the genetic mutant (GM) repository number, tissue, passage number, culture medium, submitter, age, sex, race, genetic status, verification and remarks . Appreciation is expressed to the many investigators who help the NIGMS Advisory Committee and the Repository staff select repre- sentative subjects and help validate the genetic defects by pro- viding clinical and laboratory data or assays on the cell culture. Interested investigators are invited to utilize the Repository as a source of genetic mutant cell cultures. Lewis L. Coriell, M.D., Ph.D. Arthur E. Greene, D. Sc. II. PROCEDURES FOR ORDERING GENETIC MUTANT CULTURES 1. REQUIREMENTS The cells are distributed only to qualified professional persons who are associated with recognized research, medical, educational or industrial organizations engaged in health-related research or health delivery. Before fibroblast cells can be shipped, the assurance form (Par. 10) must be signed and returned to the Repository. This is adequate for most cell cultures in the Repository. However, lymphoblast or virus transformed cell cultures require prior agreement to observe the Minimum Safety Guidelines (Page 12) and return of the signed Agreement on Lymphoid and Virus Transformed Cells (Par. 11). These forms may be obtained by writing to the Repository, or may be photocopied. 2. PROCEDURE Requests for cell cultures must be submitted on institutional purchase forms including purchase order numbers. Purchasing agents should indicate the name of the investigator on such orders. Tele- phone orders will be accepted when accompanied by a purchase order number, and should be confirmed within several days by letter. Each culture requested should include the Genetic Mutant Repository number (GM number), and the diagnosis. 3. ADDRESS All requisitions should be addressed to: Dr. Arthur E. Greene The Human Genetic Mutant Cell Repository Institute for Medical Research Copewood and Davis Streets Camden, New Jersey 08103 Telephone 609-966-7377 4. FEES The fee for each 25 cm2 flask of cells is $20.00 to non- profit institutions, but is reduced one dollar per culture up to 5 orders received simultaneously i.e. $19.00 each for an order of 2 cultures, $16.00 each for 5 or more. Frozen ampules are not shipped, because experience has shown much better success in shipping freshly revived flask cultures. Mass production of cell cultures is not a function of the Repository, (See Appendix E). The Repository is designed to provide only seed cultures. It is suggested that the recipient store aliquots of early passages in liquid nitrogen as insurance against contamination, accidents, artifacts associated with aging, and loss of the culture. 5. SHIPPING CHARGES The shipping charges are prepaid and will be added to the invoice at the time of billing. 6. HOW SHIPPED All cell cultures are grown and frozen in antibiotic-free media to aid in detection and prevention of contamination. Cell cultures in the Repository have been tested and found free of mycoplasma, bacteria, molds and fungi during characterization, at the time of frozen storage, and after recovery from liquid nitrogen. When an order is received, a frozen ampule is usually recovered from liquid nitrogen on the following Thursday and the medium is changed on Friday. The following Monday, the culture is inspected, the medium is removed and the T25 flask is filled with fresh medium, packed and shipped, usually by air mail special delivery. The flask is enclosed within two watertight plastic envelopes within a styrofoam box in a cardboard mailer to prevent leakage, overheating or freezing during shipment. A return postcard is enclosed. Please return the postcard with notations about the condition on arrival. Pertinent suggestions to improve the effectiveness of the Repository are appreciated. 7. DESCRIPTIVE DATA Each shipment contains descriptive data about the cell culture, suggested directions for cell growth and pertinent references when available. Upon receipt cell cultures should be placed in the incubator at 37° C for a few hours or overnight to permit recovery from damage which may have occurred during shipment . 8. REQUEST FOR CITATION AND REPRINTS It will be greatly appreciated and will make the cell col- lection more valuable if the source and Repository number is cited in publications in which cell cultures from the Human Genetic Mutant Cell Repository are used. The Repository would appreciate receiving a reprint of such publications. 9. PUBLICATION OF DESCRIPTIVE ARTICLES ON CELL CULTURES STORED IN THE REPOSITORY Concise descriptions of some of the cultures stored in the Repository are published after characterization in Cytogenetics and Cell Genetics under the name of the individual originally submitting the culture or biopsy. These descriptions include brief clinical histories, assay methods when applicable, family pedigrees, full or partial karyotypes in the case of chromosomal aberrations, and references to previous work involving the cell lines. For a listing of these concise papers, see Appendix C, page 153. 10. ASSURANCE FORM Before cells can be shipped from the Genetic Mutant Cell Repository the recipient institution must submit a purchase order number and agree to the limitations listed below. This agreement must be renewed annually. Please sign and return originial to the Institute for Medical Research, Copewood Street, Camden, New Jersey 08103. ASSURANCE As purchaser of cell cultures from the Genetic Mutant Cell Repository we agree that such cells, their progeny, or deriva- tives will not be used in human experimentation. It is further agreed that if such use is planned, the purchaser will first ob- tain prior written approval of the Project Officer, NOl-GM-6-2119 , National Institute of General Medical Sciences. It is further agreed that cell cultures obtained from the Genetic Mutant Cell Repository will not be resold, but they may be replicated by a third party for the original purchaser. The third party shall not be allowed to resell other than to the original purchaser furnishing the material for replication and the third party shall not use such cells for human experimen- tation. Name of Institution Name of Principal Investigator Date Signature of Authorized Signature of Principal Date Official Investigator 11. AGREEMENT ON LYMPHOID AND VIRUS TRANSFORMED CELLS This document must be appropriately completed and exchanged before lymphoid and virus transformed cell lines can be trans- ferred from the Human Genetic Mutant Cell Repository to your laboratory. AGREEMENT The potential hazardous nature of these human cell lines is unknown. However, in view of this lack of knowledge, it is appropriate that the scientific community be made aware that a potential hazard may exist. Therefore, we recommend that the enclosed guidelines for laboratory procedure be adhered to in the handling of lymphoid and virus transformed cell lines. They are also recommended for handling all cell cultures. It is understood that you will not further distribute cell lines sent to you to laboratories not under your direct super- vision. It is further agreed that all cultures obtained from the Human Genetic Mutant Cell Repository may only be replicated by a third party if the third party also executes an Agreement on Lymphoid and Virus Transformed Cells agreeing to follow the Minimum Safety Guidelines. As purchaser of cell cultures from the Human Genetic Mutant Cell Repository we agree that such cells, their progeny, or derivatives will not be used in human experimentation. It is 10 further agreed that if such use is planned, the purchaser will first obtain prior written approval of the Project Officer, NOl-GM-6-2119, National Institute of General Medical Sciences. This agreement, when appropriately executed, will be on file and will qualify you to receive lymphoid and virus transformed cell lines from the Human Genetic Mutant Cell Repository. AGREEMENT ON LYMPHOID AND VIRUS TRANSFORMED CELLS We the signatories below, have read and understand this document and agree that in the handling of cell lines furnished, we will adhere to the procedures and recommendations outlined in the foregoing and the attached "Minimum Safety Guidelines Recommended for Working with Lymphoid and Virus Transformed Human Cell Lines." A. For the recipient laboratory: Investigator: Signature Date Title Head of Signature Date Laboratory or Immediate Title Supervisor : Address B. For Human Genetic Mutant Cell Repository: Signature Date Title 11 III. HUMAN GENETIC MUTANT CELL REPOSITORY MINIMUM SAFETY GUIDELINES RECOMMENDED FOR WORKING WITH LYMPHOID AND VIRUS TRANSFORMED HUMAN CELL LINES* A. Supervision 1. Administrative Responsibilities a. Responsibility of Management Management should establish a biohazards committee to insti- tute and enforce a health and safety policy which includes a specific safety program for work involving human cell lines. The program should meet applicable federal, state and local regulations and include safety training, maintenance of accident records, and provisions for emergency treatment. b. Responsibility of the Principal Investigator The principal investigator is responsible for the prepara- tion of safety protocols for the research program under his direction. The protocols should include appropriate procedures for use, storage, decontamination, disposal and emergency treat- ment. The protocols should be approved by the biohazards *These guidelines were developed on February 11, 1974 at a special meeting at the National Institutes of Health attended by represent- atives from the Office of Biohazards of NCI, NIAID, NIGMS and the Advisory Committee to the Human Genetic Mutant Cell Repository. 12 committee and discussed with the research staff before starting the research program. 2. Medical Surveillance and Screening a. Physical Examinations Appropriate pre-employment and periodic medical examinations are desirable for persons working with human cell lines. b. Work Restrictions Persons having reduced immunologic competency should be restricted from working with these human cell lines. c. Serum Collection Serum should be collected at the time of the pre-employment physical to establish a baseline reference. Serum should be re- collected and stored annually. Serum should be collected immedi- ately after accidental injection or ingestion and at an appropriate interval thereafter. For those individuals exposed to long terra lymphoid lines or their derivatives, anti-EB virus titers should be obtained on the collected sera. 3. Laboratory Access Access to the cell culture area should be restricted to persons directly working with the cell lines, or by specific authorization by the principle investigator or director of the laboratory . B. Personnel Practices 1. Pipetting 13 Mechanical pipetting aids rather than mouth pipetting should be used for all pipetting procedures. 2. Eating, Drinking and Smoking Eating, drinking and smoking should not be allowed in the same areas where cell lines are under study. 3. Protective Clothing It is recognized that the criteria for protective clothing may vary according to the physical situation of the laboratory and the agents handled. Ideally, adequate protective clothing such as a fully fastened laboratory coat should be worn. This clothing should not be worn outside the work area once the work area has been entered. C. Physical Control Practices (Recommended for all cell lines, but required for long term lymphoid lines and their deri- atives) . 1. Ventilated Safety Cabinets or Hoods Ventilated safety cabinets and hoods and other safety apparatus should be employed and should be tested at least annually to certify correct containment and operation. A list of speci- fications for satisfactory hoods and instructional materials may be obtained from the Office of Biohazards, NCI. 2. Housekeeping Appropriate housekeeping procedures which suppress the 14 formation of aerosols should be used. Working surfaces should be wiped down with an appropriate disinfectant before and after work with each cell culture and at the end of the working day. 3. Decontamination and Disposal Contaminated glassware and similar materials should be appropriately decontaminated or stored for decontamination before removal from the work area for recycling or disposal. Liquid wastes should be decontaminated either chemically or by heat, before being discharged to the community sanitary sewer system. 4. Protection of Vacuum Lines Vacuum services, if used, should be protected with disposable absolute air filters and liquid traps. The effluent should be collected in liquid traps containing concentrated disinfectant. References Biohazards in Biological Research, ed. A. Hellman, M.N. Oxman and P. Pollack. Cold Spring Harbor Laboratory, New York (1973). National Cancer Institute Specification: General Purpose Clean Air Biological Safety Cabinet. 15 IV. SUBMISSION OF SPECIMENS TO THE REPOSITORY Biopsies are preferred to established cell cultures because they can be processed and stored in lower passage. When submitting a specimen to the Repository, the biopsy should be placed in a 25 cm tissue culture flask or screw top vial with culture medium containing 100 units/ml of penicillin and 100 mcg/ml of streptomycin. Tape the top or cap of the flask very securely to prevent leakage. Package the biopsy flask in a container so that it will not be broken in transit. Mark on the outside of the package that it should be kept at room temperature and not refrigerated, frozen or overheated. Early passage cultures may be submitted when a biopsy cannot be obtained from the patient. The culture flask (25 cm preferably) should be filled to the top with culture medium and shipped as described above. Mail biopsy or culture the same day by air mail special delivery to: Dr. Arthur E. Greene Human Genetic Mutant Cell Repository Institute for Medical Research Copewood and Davis Streets Camden, New Jersey 08103 Phone 609-966-7377 Before a biopsy or cell culture can be processed for the 16 Repository, documented proof of the diagnosis must be provided on a submission sheet which is available from the Institute for Medical Research, or may be photocopied by the submitter from pages 18-22. Without this information the culture cannot be coded into the information retrieval system or be of value to users of the Repository; and to conserve effort and expense the Repository staff are instructed not to process a specimen unless documentation of diagnosis is provided with the specimen. Sub- mitters are therefore requested to fill in all applicable blanks on the submission sheets. Please provide a family genealogy if appropriate . No biopsies or cell cultures submitted to the Human Mutant Cell Repository are to be obtained from a live fetus, defined by the presence of pulse, circulation and other vital signs. 17 SUBMISSION SHEET Please Complete Every Item that Applies . TO BE FILLED IN BY I MR Date Received / / GM # Mo. Day Year Contamination ? 1 Failure SPECIES: \T\ HUMAN (Go to Item 1) \Y\ OTHER_ (Go to Item 8) ( Specify) 1. Initials: 2A. Date of Birth / / or Age: Mo. Day Year 2B. Gestational Age if Amniotic Fluid or Fetus: Days Wks. Mos. Yrs. "(Circle One) Wks. (Circle One) 3. Sex: [T] Male [T] Female [3J Ambiguous [4] Not Recorded 4. A. Race: |T] white |Y| Black [T] Oriental [4] Other ( Specify) B. Ethnic Background if Relevant to the Disorder: (Especially Useful for Inborn Errors of Metabolism) M PL, 5. Clinical Phenotype: [T] Clinically Normal [2] Clinically Affected [T] No Information 6. Clinical Manifestations/Diagnosis: (Please List) A. B. C. D. E. 7. Source(s) of Clinical Information: (Check One or More) |T1 Personal Examination [3] Autopsy Records |"2~| Hospital Records {b] Private Physician [3J Genetic Clinic Records (7] Other [4~1 Specialist's Report (Specify) s M M a H 8. Local Culture/Lab/Biopsy Identification Number: 9. Type of Sample: \T\ Culture if Passages When Submitted Date of Origin / / Mo. Day Year Date Submitted / / Mo . Day Year 10. Tissue of Origin [T] Peripheral Blood [2~1 Bone Marrow 131 Amniotic Fluid \2\ Biopsy [3j Blood Date Obtained / / Mo. Day Year [4] Skin 00 Other Specify 18 11 Culture Medium in which Submitted: m McCoys Eagle-Hanks ' Eagle-Ear le /o RPMI-1640 Fetal Calf LO % [21 1 Serum % [31 % Inactivated m Ham's F-12 % a Uninactivated [5] [81 Ham's F-10 Other % > 12. Additioi Antibacl UJ No H] Yes m m 0 utner CO CX o pq a D H O l of Following :erial Agents? Penicillin Streptomycin Gentamycin Other to C % % % % ( Specify) ulture? Antifungal (Yeast)? UJ No CO Yes fll Fungizone [2] Mycostatin [3] Other Other Additives? [lj No [2] Yes (List) ( Specify) 13. Special Instruct ion(s ) on Handling or Freezing of Culture/Biopsy? Q] No [2j Yes ( Specify) 14. Have Chromosome Studies ever been Done on this Individual? |T| Information Not Available (Go to Item 22) [2] No (Go to Item 22) [T| No, but Studies are Underway (Go to Item 22) [4] Yes [T] On Cells from this Culture [2] On Cells from Other Tissue/Samples 15. General Karyotype Results: \T\ Normal [2] Abnormal \T\ Balanced [2j Unbalanced [3J Not Certain 16. Sex Chromosomal Complement: (Check One or More) LH XX [2] XO [3j XXX [4] XY [3J XXY [H XYY [7] XXXY [8j Other ( Specify) 17. Autosomal Mosaicism? [T] Detected (If so, # and % Sub Lines: w H to o § CO § a Not Detected Suspected 19 CO to o CO w H to < M w « o o Breakage/Somatic Rearrangements? [T] Data Not Available 2 Data Available (T) J Breaks Observed [2~| ^ Somatic Rearrangements 5 Observed ^ [3] Neither Observed o 19. Current International Nomenclature: ______ CO o 2 O 20. The Above Karyotype is Based on \T\ Banded or _] Unbanded Technique (s ) . 21. If Banded, what Staining Method(s) was Used: 22. Have Biochemical Studies been Done on this Individual __ No (Go to Item 29) CD Yes |T| On Cells from this Culture (Go to Item 23) jT| On Other Cultures or Tissues from Same Patient (Go to Item 28) 23. Specific Defect Detected or Investigated: 24. Assay Method Used: 25. Assay Level in this Cell Culture: 3 26. Assay Level in Normal Control Cell Cultures 27. Conclusion Based on Biochemical Assay: [T] Normal |T| Abnormal [3] Inconclusive Consistent with Heterozygosity [T| Consistent with Homozygosity j3] Genotype Uncertain [3 Not Applicable 20 28. Significant Laboratory Data on Other Cell Cultures or Tissues from this Individual : Tissue Assay Level Conclusion (See Item 27) 29, Is Pedigree Available? No Yes o 30. Relative Chrom. Studies Done? Biochem. Studies Done? Clinical Lab Studies Done? Cultures Available? Banked in Camden? CO Father re Mother 3 Siblings Offspring PL, Other ( Specify) CO CO o ►J u 55 W CO H 55 31. 32. 33. Has this Pat ient /Family been Reported in Literature? [j] No LH Yes Specify Reference Has a Sample from this Patient been Previously Stored in Camden? Q] No [3 Yes, GM # . Any Additional Comments/Observations/References/Lab Studies on Culture, Patient, Family Etc.? o c_> Enclosures: [JJ Pedigree |T) Clinical History/Description of Patient and/or Family [31 Karyotype {U\ Laboratory Data on Patient/Family [31 Reprint of Reference \b\ Other (Specify) 21 To encourage storage of unusual cell cultures in the Repository, provision has been made for delayed release to other investigators if the contributor so desires. Please check your preference: a) release culture to anyone requesting it , b) release only to contributor during the first year . At the conclusion of 1 year the cell culture will be listed in the next printing of the catalog and made available to other investigators unless additional time is specifically requested. I hereby grant permission for these cells to be stored in a bank of genetic mutant cell cultures and the progeny cells distributed to qualified investigators. Appropriate consent was obtained from the patient from whom the cells were originally obtained, or can be reason- ably inferred, for use of these cells for diagnosis, research, teaching or therapy. No biopsies or cell cultures submitted to the Human Mutant Cell Repository are to be obtained from a live fetus, defined by the presence of pulse, circulation and other vital signs. Date Submitter ( Signature) Address Telephone Number Mail completed form with, or preferably preceeding shipment of cell cultures, to: Dr. Arthur Greene, Institute for Medical Research, Copewood and Davis Streets, Camden, New Jersey 08103. Phone: 609-966-7377. 22 EXPLANATION OF THE CODE INTERPRETING RECORDED DATA IN THE COLUMNS OF THE CATALOG COLUMN GM #: The GM number of the cell culture, refers to the number assigned to the culture when it was received at the Human Genetic Mutant Cell Repository. Fibroblast cultures are all originated from skin unless noted in the Remarks column. Lymphocyte cultures are all established from peripheral blood. McKusick's number is inserted following the name of each disease.* Passage #: The number of serial in vitro transfers of the cell culture as stored in liquid nitrogen. Culture Medium: For code see appendix A, page 131. Submitter Code: A number" which identifies the investigator who submitted the biopsy or culture to the Repository. For code see appendix B, page 133. Age : Age of the donor is expressed in years, or when appropri- ate in months (mo.), weeks (wk.) or days (da.). F indicates fetus . Sex: M or F Race: W-Caucasian; B-black; 0-Oriental ; I-Indian (India); P-Puerto Rican. Space left empty if race unknown. *McKusick, Victor. Mendelian Inheritance in Man 4th Edition. John's Hopkins Press, Baltimore, London. 1975. 23 Genetic Status: + y 7 (0) Normal gene Affected gene Heraizygous for X-linked trait At risk for autosomal trait, genetic status not determined Carrier for trait as determined by pedigree or clinical diagnosis The McKusick* number immediately following the name of the disease will indicate the dominant, recessive, or X-linked nature of the disease. The first digit is one for a dominant disease (e.g. Huntington Chorea - 14310), two for a recessive disease (e.g. Tay-Sachs Disease - 27280), and three for an X-linked trait (e.g. Lesch Nyhan Syndrome - 30800). Verified : B if the defect was verified on the cell culture before freezing, A if verified after recovery from liquid nitrogen. Space left blank if verified on another cell culture or tissues from the same patient or relative, if not verified at all, or if verification is not yet possible because defect is unknown or not yet expressed in culture. Paris Nomenclature: As described (Paris Conference 1971) and Supplement (1975): Standardization in Human Cytogenetics. Birth Defects: Original Article Series, VIII:7, 1972. The National Foundation, New York. *McKusick, Victor. Mendelian Inheritance in Man 4th Edition. John's Hopkins Press, Baltimore, London. 1975. 24 Balanced, Unbalanced: Balanced (B) or Unbalanced (U) karyotype Remarks: Any pertinent information not included in preceding columns . *after GM #: Means a description of this cell culture has been published in Cytogenetics and Cell Genetics. Reference numbers appearing in parentheses at the bottom of the page refer to these publications listed in Appendix C, pages 153-160. Aging Cell Repository: Cell cultures listed under this heading are of particular interest to investigators interested in studies on aging. Some cultures originally deposited in the GM Repository are also of interest to the Aging Repository. For convenience these cell cultures are listed in both the GM and the Aging (AG) Repository. Many new cell cultures are now being added to the Aging Repository and receive an AG #. Double listings will be made when appropriate. Requests for these cells may be addressed to the Director of the Aging Repository: Dr. Warren W. Nichols Institute for Medical Research Copewood Street Camden, New Jersey 08103 Telephone 609-966-7377 Procedures and charges are the same as for the Genetic Mutant Cell Repository. 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