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The Emerging Technology and Application of Preimplantation Genetic Diagnosis

Published online by Cambridge University Press:  01 January 2021

Richard J. Tasca  and
Michael E. McClure
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Extract

Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis (PGD) provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.

PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment of pregnancy. The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization (IVF). In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell(s), or a polar body, is placed into a tube for single gene analysis (DNA analysis by polymerase chain reaction (PCR)), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide (fluorescence in situ hybridization (FISH)).

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Article
Information
Journal of Law, Medicine & Ethics , Volume 26 , Issue 1 , Spring 1998 , pp. 7 - 16
Copyright
Copyright © American Society of Law, Medicine and Ethics 1998

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References

See, for example, Fujimura, J.H., Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge: Harvard University Press, 1996); and Friedman, J.M., “Genetics and Epidemiology, Congenital Anomalies and Cancer,” American Journal of Human Genetics, 60 (1997): 469–73.Google Scholar
See, for example, Scott, W.K. Pericak-Vance, M.A. Haines, J.L., Letter, “Genetic Analysis of Complex Diseases,” Science, 275 (1997): 1327; Bell, D.A. Taylor, J. A., Letter, “Genetic Analysis of Complex Diseases,” Science, 275 (1997): 1327–28; Long, A.D. Grote, M.N. Langley, C.H., Letter, “Genetic Analysis of Complex Diseases,” Science, 275 (1997): 1328; Muller-Myhsok, B. Abel, L., Letter, “Genetic Analysis of Complex Diseases,” Science, 275 (1997): 1328–29; Merikangas, K., Letter, “Genetic Analysis of Complex Diseases,” Science, 275 (1997): 1329–30; Risch, N. Merikangas, K., “The Future of Genetic Studies of Complex Human Diseases,” Science, 273 (1996): 1516–17; and Sawcer, S. Goodfellow, P.N. Compston, A., “The Genetic Analysis of Multiple Sclerosis,” Trends in Genetics, 13 (1997): 234–39.Google Scholar
See Spielman, R.S. McGinnis, R.E. Ewens, W.J., “Transmission Test for Linkage Disequilibrium: The Insulin Gene Region and Insulin-Dependent Diabetes Mellitus (IDDM),” American journal of Human Genetics, 52 (1993): 506–11; and Mitchell, L.E., “Differentiating Between Fetal and Maternal Genotypic Effects Using the Transmission Test for Linkage Disequilibrium,” American Journal of Human Genetics, 60 (1997): 1006–07.Google Scholar
See Sawcer, Goodfellow, Compston, , supra note 2.Google Scholar
See, for example, Kent-First, M., “A Lesson from Mosaics: Don't Leave the Genetics Out of Molecular Genetics,” Journal of NIH Research, 9 (1997): 29–33; Iarovici, D., “Anti-Integrin Blocks Osteoporosis in Rats Lacking Estrogen,” Journal of NIH Research, 9 (1997): 34–35; and Boehmer, A.L.M., “Germ-Line and Somatic Mosaicism in the Androgen Insensitivity Syndrome: Implications for Genetic Counseling,” American Journal of Human Genetics, 60 (1997): 1003–06.Google Scholar
See Crystal, R.G., “Transfer of Genes to Humans: Early Lessons and Obstacles to Success,” Science, 270 (1995): 404–10.CrossRefGoogle Scholar
See Koehn, R.K. Hilbish, T.J., “The Adaptive Importance of Genetic Variation,” American Scientist, 75 (1996): 182–89.Google Scholar
See Little, P., “Human Genetics. Woman's Meat, a Man's Poison,” Nature, 382 (1996): 494–95; and Post, S.G., “The Clinical Introduction of Genetic Testing for Alzheimer Disease. An Ethical Perspective,” JAMA, 277 (1997): 832-36.Google Scholar
See Giardiello, F.M., “The Use and Interpretation of Commercial APC Gene Testing for Familial Adenomatous Polyposis,” N. Engl. J. Med., 336 (1997): 823–27.CrossRefGoogle Scholar
See Neel, J., “A Program for Genetics in a World of Desperate Scarcities,” in Mattern, M., ed., Moral Education V (Cold Spring Harbor: Cold Spring Harbor Press, 1995): 45–73; Leonard, H.B. Zeckhauser, R.J., “Cost-Benefit Analysis Applied to Risks: Its Philosophy and Legitimacy,” in Beauchamp, T.L. Walters, L., eds., Contemporary Issues in Bioethics (Belmont: Wadsworth, 3rd ed., 1989): 607–18; Modell, B. Kuliev, A.M., “A Scientific Basis for Cost-Benefit Analysis of Genetic Services,” Trends in Genetics, 9 (1993): 46–51; Hidlebaugh, D.A. Thompson, I.E. Berger, M.J., “Cost of Assisted Reproductive Technologies for a Health Maintenance Organization,” Journal of Reproductive Medicine, 42 (1997): 570–74; and Davis, D.S., “Genetic Dilemmas and the Child's Right to an Open Future,” Rutgers Law Journal, 28 (1997): 549–92.Google Scholar
See Verlinsky, Y., Abstract, “Preimplantation Diagnosis of Age-Related Aneuploidies by First and Second Polar Body FISH Analysis,” Journal of Assisted Reproduction and Genetics, 14 (1997): 477.Google Scholar
See Scriver, C.R., eds., The Metabolic and Inherited Bases of Inherited Disease (New York: McGraw-Hill, 7th ed., 1995); and Welsh, M.J., “Cystic Fibrosis,” in Scriver, , id. at 3799–876.Google Scholar
See Sanders, J.S. Pryor, T.D. Wedel, M.K., “Prolonged Survival in an Adult with Cystic Fibrosis,” Chest, 11 (1980): 226–27.Google Scholar
See Gibson, L.E. Cooke, R.E., “A Test for Concentration of Electrolytes in Sweat in Cystic Fibrosis of the Pancreas Utilizing Pilocarpine by Iontophoresis,” Pediatrics, 23 (1959): 545.Google Scholar
See Collins, F.S., “Cystic Fibrosis: Molecular Biology and Therapeutic Implications,” Science, 256 (1992): 774–83.Google Scholar
See Gravel, R.A., “The GM2 Gangliosidoses,” in Scriver, , supra note 12, at 2838–78.Google Scholar
See id. at 2859.Google Scholar
See id. at 2862.Google Scholar
Worton, R.G. Brooke, M.H., “The X-Linked Muscular Dystrophies,” in Scriver, , supra note 12, at 4195–226.Google Scholar
Gussoni, E. Blau, H.M. King, L.M., “The Fate of Individual Myoblasts after Transplantation into Muscles of DMD Patients,” Nature Medicine, 3 (1997): 970–77.Google Scholar
Emery, A.E.H., Duchenne Muscular Dystrophy (New York: Oxford University Press, 2nd ed., 1993).Google ScholarPubMed
See Gussoni, Blau, King, , supra note 20.Google Scholar
See Caskey, C.T., “Triplet Repeat Mutations in Human Disease,” Science, 256 (1992): 784–88; and Sutherland, G.R. Molley, J.C. Richards, R.I., “Fragile X Syndrome: The Most Common Cause of Familial Intellectual Handicap,” Medical Journal of Australia, 158 (1993): 482–85.Google Scholar
See Beaudet, A.L., “Genetics, Biochemistry, and Molecular Basis of Variant Human Phenotypes,” in Scriver, , supra note 12, at 67.Google Scholar
See Caskey, , supra note 23.Google Scholar
See id.Google Scholar
See Beaudet, , supra note 24; and Epstein, C., “Down Syndrome (Trisomy 21),” in Scriver, , supra note 12, at 749–94.Google Scholar
See Warburton, D., “Cytogenetic Abnormalities in Spontaneous Abortions of Recognized Conceptions,” in Porter, I.H. Willey, A., eds., Perinatal Genetics: Diagnosis and Treatment (New York: Academic Press, 1986): 133–48.Google Scholar
See Thompson, J.S. Thompson, M.W., eds., Genetics in Medicine (Philadelphia: W.S. Saunders, 1986); and Beaudet, , supra note 24.Google Scholar
For a very comprehensive view of genetic diseases, see Metabolic and Molecular Bases of Inherited Disease. See Scriver, , supra note 12.Google Scholar
See Scriver, C.R., “The Frequency of Genetic Disease and Congenital Malformation among Patients in a Pediatric Hospital,” Canadian Medical Association Journal, 108 (1973): 1111–15; Baird, P.A., “Genetic Disorders in Children and Young Adults: A Population Study,” American Journal of Human Genetics, 42 (1988): 677–93; Galjaard, H., Genetic Metabolic Diseases: Early Diagnosis and Prenatal Analysis (Amsterdam: Elsevier, 1980); Delhanty, J.D.A. Handyside, A.H., “The Origin of Genetic Defects in the Human and their Detection in the Preimplantation Embryo,” Human Reproduction Update, 1 (1995): 201–15; and McKusick, V.A., Mendelian Inheritance in Man (Baltimore: Johns Hopkins Press, 1992).Google Scholar
See Beaudet, , supra note 24, at 67; and see Galjaard, , supra note 31.Google Scholar
See Delhanty, Handyside, , supra note 31.Google Scholar
See Wilcox, J.A., “Incidence of Early Loss of Pregnancy,” N. Engl. J. Med., 319 (1988): 189–94.Google Scholar
See Beaudet, , supra note 24, at 69.Google Scholar
See Saiki, R.K., “Primer-Directed Enzymatic Amplification of DNA with a Thermostabile DNA Polymerase,” Science, 239 (1988): 487–91.Google Scholar
See Delhanty, J.D.A., “Multicolor FISH Detects Frequent Chromosomal Mosaicism and Chaotic Division in Normal Preimplantation Embryos from Fertile Patients,” Human Genetics, 99 (1997): 755–60.CrossRefGoogle Scholar
See Munné, S., “The Use of First Polar Bodies for Preimplantation Diagnosis of Aneuploidy,” Human Reproduction, 10 (1995): 1014–20; and Dyban, A., “Detection of Aneuploidy in Human Oocytes and Corresponding First Polar Bodies by Fluorescent In Situ Hybridization,” Journal of Assisted Reproduction and Genetics, 13 (1996): 73–78.Google Scholar
See Handyside, A.H. Delhanty, J.D.A., “Preimplantation Genetic Diagnosis: Strategies and Surprises,” Trends in Genetics, 13 (1997): 270–75.Google Scholar
See McClure, M.E., “The ART of Medically-Assisted Reproduction: An Embryo is an Embryo is an Embryo,” in Thomasma, D.C. Kushner, T., eds., Birth to Death: Science and Bioethics (New York: Cambridge University Press, 1996): 35–49.Google Scholar
See Hardy, K., “Human Preimplantation Development In Vitro Is Not Adversely Affected by Biopsy at the 8-Cell Stage,” Human Reproduction, 5 (1990): 708–14; Pierce, K.E., “Preimplantation Development of Mouse and Human Embryos Biopsied at Cleavage Stages Using a Modified Displacement Technique,” Human Reproduction, 12 (1997): 351–56.Google Scholar
See Delhanty, , supra note 37.Google Scholar
See Harris, J.A. James, L., “State-by-State Cost of Birth Defects—1992,” Teratology, 56 (1997): 11–12.3.0.CO;2-4>CrossRefGoogle Scholar
See Handyside, Delhanty, , supra note 39.Google Scholar
See El-Hashemite, N. Wells, D. Delhanty, J.D.A., Letter & Comment, “Preimplantation Genetic Diagnosis of Beta-Thalassaemia,” Lancet, 348 (1996): 620.Google Scholar
See Findlay, I., “Simultaneous DNA ‘Fingerprinting,’ Diagnosis of Sex and Single-Gene Defect Status from Single Cells,” Human Reproduction, 10 (1995): 1005–13; and Findlay, I., Abstract, “Fluorescent PCR in Single Cells,” Journal of Assisted Reproduction and Genetics, 14 (1997): 439–40.Google Scholar
See Grifo, J.A., Abstract, “Preimplantation Genetic Diagnosis of Marfan's Syndrome Using Single Cell PCR and Restriction Endonuclease Digestion,” Journal of Assisted Reproduction and Genetics, 14 (1997): 441.Google Scholar
See Ray, P.F. Handyside, A.H., “Increasing the Denaturation Temperature During the First Cycles of Amplification Reduces Allele Dropout from Single Cells for Preimplantation Genetic Diagnosis,” Molecular Human Reproduction, 2 (1996): 213–18.Google Scholar
See Handyside, Delhanty, , supra note 39.Google Scholar
See Zhang, L., “Whole Genome Amplification from a Single Cell: Implications for Genetic Analysis,” Proceedings of the National Academy of Sciences, 89 (1992): 5847–51; and see Delhanty, Handyside, , supra note 31.Google Scholar
See Xu, K.P., “Primer Extension Preamplification for Detection of Multiple Genetic Loci from Single Human Blastomeres,” Human Reproduction, 8 (1993): 2206–10.Google Scholar
See Harper, J.C., “Identification of the Sex of Human Preimplantation Embryos in Two Hours Using an Improved Spreading Method and Fluorescent In-Situ Hybridization (FISH) Using Directly Labelled Probes,” Human Reproduction, 9 (1994): 721–24.CrossRefGoogle Scholar
See Speicher, M.R. Gwyn Ballard, S. Ward, D.C., “Karyotyping Human Chromosomes by Combinatorial Multi-Fluor FISH,” Nature Genetics, 12 (1996): 368–75; and Weier, H.-U.G., Abstract, “Spectral Imaging in Preconception/Pre-implantation Genetic Diagnosis (PGD) of Aneuploidy: Multi-Color, Multi-Chromosome Screening of Single Cells,” journal of Assisted Reproduction and Genetics, 14 (1997): 479.CrossRefGoogle Scholar
See Handyside, A.H., “Preimplantation Genetic Diagnosis Today,” in Edwards, R.G. Beard, H.K. Howles, C.M., eds., Human Conception In Vitro, 1995 (Oxford: Oxford University Press, 1995): 139–51.Google Scholar
See id.Google Scholar
See Delhanty, , supra note 37.Google Scholar
See id.Google Scholar
See Verlinsky, , supra note 11.Google Scholar
See Handyside, , supra note 54.Google Scholar
See Carson, S., presentation at “Introducing Innovations into Practice: Technical and Ethical Analyses of Preimplantation Genetic Diagnosis and Intracytoplasmic Sperm Injection Technologies” Bethesda, Maryland (June 19, 1992) (on file with authors); and Handyside, A., presentation at “Introducing Innovations into Practice: Technical and Ethical Analyses of Preimplantation Genetic Diagnosis and Intracytoplasmic Sperm Injection Technologies” Bethesda, Maryland (June 19, 1992) (on file with authors).Google Scholar