First published in 1966, Thompson and Thompson Genetics and Genomics in Medicine has become an essential textbook for medical students, genetic counseling students, students in laboratory medicine, and more advanced trainees. With its focus on fundamental principles in human genetics and genomics and their application to medicine, the book has served many as a well-thumbed resource they return to over and over. Such students can continue to depend on this valuable text, joining those in newer fields of genome data analysis for all they need to know about genetics and genomics throughout their basic science training, clinical placements and beyond. Coverage includes new discoveries—such as the functional roles of non-coding RNAs, chromatin regulation and epigenetics—latest technologies, and new diagnoses they are enabling. Under an expanded title, this ninth edition has been completely revised by a new editorial team overseeing a large cadre of contributing authors. Support groups have also assisted to update illustrations featuring beautiful images of those living with genetic conditions.
1. Chapter 1. Introduction - p. 1 2. Chapter 2. Introduction to the Human Genome - p. 5 3. Chapter 3. The Human Genome: Gene Structure and Function - p. 23 4. Chapter 4. Human Genetic Diversity: Human Genetic Diversity: Genomic Variation - p. 45 5. Chapter 5. Principles of Clinical Cytogenetics and Genome Analysis - p. 61 6. Chapter 6. The Chromosomal and Genomic Basis of Disease: Disorders of the Autosomes and Sex Chromosomes - p. 79 7. Chapter 7. Patterns of Single-Gene Inheritance - p. 109 8. Chapter 8. Principles of Clinical Epigenetics - p. 135 9. Chapter 9. Complex Inheritance of Common Multifactorial Disorders - p. 149 10. Chapter 10. Population Genetics for Genomic Medicine - p. 175 11. Chapter 11. Identifying the Genetic Basis for Human Disease - p. 203 12. Chapter 12. The Molecular Basis of Genetic Disease - p. 231 13. Chapter 13. The Molecular, Biochemical, and Cellular Basis of Genetic Disease - p. 251 14. Chapter 14. The Treatment of Genetic Disease - p. 293 15. Chapter 15. Developmental Genetics and Birth Defects - p. 321 16. Chapter 16. Cancer Genetics and Genomics - p. 347 17. Chapter 17. Genetic Counseling and Risk Assessment - p. 373 18. Chapter 18. Preconception and Prenatal Screening and Diagnosis - p. 391 19. Chapter 19. Application of Genomics to Medicine and Individualized Health Care - p. 411 20. Chapter 20. Ethical and Social Issues in Genetics and Genomics - p. 425 21. Clinical Case Studies Illustrating Genetic Principles - p. 435 22. Case Presentations - p. 435 23. 1. Abacavir-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (MIM 608579) (Genetically Determined Immunological Adverse Drug Reaction) - p. 435 24. 2. Achondroplasia (MIM 100800) (FGFR3 Pathogenic Variant) - p. 437 25. 3. Age-Related Macular Degeneration (MIM 603075) (Complement Factor H Variants) - p. 440 26. 4. Alzheimer Disease (MIM 104300) - p. 443 27. 5. 16p11.2 Deletion Syndrome (MIM 611913) - p. 446 28. 6. Beckwith-Wiedemann Syndrome (MIM 130650) (Uniparental Disomy and Imprinting Defect) - p. 449 29. 7. Hereditary Breast and Ovarian Cancer (MIM 604370, 612555) (BRCA1 and BRCA2 Pathogenic Variants) - p. 453 30. 8. Charcot-Marie-Tooth Disease Type 1 A (MIM 118220) (PMP22 Sequence Variant or Duplication) - p. 455 31. 9. CHARGE Syndrome (MIM 214800) (CHD7 Disorder) - p. 457 32. 10. Chronic Myelogenous Leukemia (MIM 608232) (BCR-ABL1 Oncogene) - p. 459 33. 11. Inflammatory Bowel Disease (MIM 266600) - p. 461 34. 12. Cystic Fibrosis (MIM 219700) (CFTR Pathogenic Variants) - p. 464 35. 13. Hearing Loss (NonSyndromic) (MIM 220290) (GJB2 Pathogenic Variants) - p. 469 36. 14. Duchenne Muscular Dystrophy (MIM 310200) (Dystrophin [DMD] Pathogenic Variants) - p. 471 37. 15. Monogenic Diabetes (MIM 600496) (Single Gene Pathogenic Variants Impacting Pancreatic Islet β Cell Development and/or Function) - p. 474 38. 16. Familial Hypercholesterolemia (MIM 143890) (Low-Density Lipoprotein Receptor [LDLR] Variants) - p. 478 39. Principles - p. 480 40. Major Phenotypic Features - p. 480 41. History and Physical Findings - p. 480 42. Background - p. 480 43. Questions for Small Group Discussion - p. 482 44. References - p. 482 45. 17. Fragile X Syndrome (MIM 300624), Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS) (MIM 300623), and Fragile X–Associated Primary Ovarian Insufficiency (FXPOI) (MIM 311360) (Pathogenic FMR1 Repeat Expansion) - p. 482 46. 18. GAUCHER DISEASE Type I (Non-Neuronopathic) (MIM 230800) (GBA Pathogenic Variants) - p. 486 47. 19. Glucose-6-Phosphate Dehydrogenase Deficiency (MIM 300908) (G6PD Pathogenic Variants) - p. 490 48. 20. Hereditary Hemochromatosis (MIM 235200) (HFE Pathogenic Variants) - p. 494 49. 21. Hemophilia (MIM 306700 and MIM 306900) (F8 or F9 Pathogenic Variants) - p. 497 50. 22. 22q11.2 Deletion Syndrome (MIM 188400 DiGeorge Syndrome or MIM 192430 Velocardiofacial Syndrome) - p. 500 51. 23. Holoprosencephaly (Nonsyndromic Form) (MIM 142945) (Sonic Hedgehog [SHH] variants) - p. 504 52. 24. Huntington Disease (MIM 143100) (HTT Pathogenic Variant [CAG Expansion]) - p. 508 53. 25. Hypertrophic Cardiomyopathy (MIM 192600) (Cardiac Sarcomere Gene Variants) - p. 512 54. 26. Proteus Syndrome (MIM 176920) (AKT1 Gene de novo Mosaic Variant) - p. 515 55. 27. Fetal Growth Restriction (Abnormal Fetal Karyotype) - p. 518 56. 28. Long QT Syndrome (MIM 192500) (Cardiac Ion Channel Gene) - p. 522 57. 29. Lynch Syndrome (MIM 120435) (DNA Mismatch Repair Genes Pathogenic Variants) - p. 526 58. 30. Marfan Syndrome (MIM 154700) (FBN1 Pathogenic Variants) - p. 529 59. 31. Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MIM 201450) (ACADM Pathogenic Variation) - p. 532 60. 32. Miller-Dieker Syndrome (MIM 247200) (17p13.3 Heterozygous Deletion) - p. 536 61. 33. Myoclonic Epilepsy With Ragged-Red Fibers (MIM 545000) (Mitochondrial tRNAlys Variant) - p. 540 62. Principles - p. 542 63. Major Phenotypic Features - p. 542 64. Case Report - p. 542 65. Background - p. 542 66. Phenotype and Natural History - p. 543 67. Management - p. 543 68. Inheritance - p. 543 69. Questions for Small Group Discussion - p. 543 70. References - p. 543 71. 34. Neurofibromatosis 1 (MIM 162200) (NF1 Pathogenic Variants) - p. 543 72. 35. Roifman Syndrome (MIM 616651) RNU4ATAC Noncoding RNA Gene Pathogenic Variants - p. 547 73. 36. Ornithine Transcarbamylase Deficiency (MIM 311250) (OTC Pathogenic Variant) - p. 550 74. 37. Polycystic Kidney Disease (MIM 173900 and MIM 613095) (PKD1 or PKD2 Pathogenic Variants) - p. 554 75. 38. Prader-Willi Syndrome (MIM 176270) (Absence of Paternally Derived 15q11-q13) - p. 558 76. 39. Retinoblastoma (MIM 180200) (RB1 Pathogenic Variants) - p. 563 77. 40. Rett Syndrome (MIM 312750) (MECP2 Variants) - p. 565 78. 41. Noonan Syndrome (RASopathies) (MIM 163950) - p. 567 79. 42. Sickle Cell Disease (MIM 603903) - p. 569 80. 43. Tay-TAY-Sachs Disease (MIM 272800) (HEXA Pathogenic Variants) - p. 571 81. 44. α-Thalassemia (α-Globin Deficiency) (MIM 604131) - p. 574 82. 45. Thiopurine S-Methyltransferase Deficiency (MIM 610460) (TPMT Variants) - p. 577 83. 46. Thrombophilia (MIM 188055 and 176860) (FV and PROC Pathogenic Variants) - p. 579 84. 47. Turner Syndrome (Female Monosomy X) Chromosomal - p. 583 85. 48. Xeroderma Pigmentosum (MIM 278700) (Defect of Nucleotide Excision Repair, XPA Pathogenic Variants) - p. 586 86. 49. Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure (MIM 614742) (TERT Pathogenic Variants) - p. 590 87. Glossary - p. 595 88. Index - p. 631
First published in 1966, Thompson and Thompson Genetics and Genomics in Medicine has become an essential textbook for medical students, genetic counseling students, students in laboratory medicine, and more advanced trainees. With its focus on fundamental principles in human genetics and genomics and their application to medicine, the book has served many as a well-thumbed resource they return to over and over. Such students can continue to depend on this valuable text, joining those in newer fields of genome data analysis for all they need to know about genetics and genomics throughout their basic science training, clinical placements and beyond. Coverage includes new discoveries—such as the functional roles of non-coding RNAs, chromatin regulation and epigenetics—latest technologies, and new diagnoses they are enabling. Under an expanded title, this ninth edition has been completely revised by a new editorial team overseeing a large cadre of contributing authors. Support groups have also assisted to update illustrations featuring beautiful images of those living with genetic conditions.
1. Chapter 1. Introduction - p. 1 2. Chapter 2. Introduction to the Human Genome - p. 5 3. Chapter 3. The Human Genome: Gene Structure and Function - p. 23 4. Chapter 4. Human Genetic Diversity: Human Genetic Diversity: Genomic Variation - p. 45 5. Chapter 5. Principles of Clinical Cytogenetics and Genome Analysis - p. 61 6. Chapter 6. The Chromosomal and Genomic Basis of Disease: Disorders of the Autosomes and Sex Chromosomes - p. 79 7. Chapter 7. Patterns of Single-Gene Inheritance - p. 109 8. Chapter 8. Principles of Clinical Epigenetics - p. 135 9. Chapter 9. Complex Inheritance of Common Multifactorial Disorders - p. 149 10. Chapter 10. Population Genetics for Genomic Medicine - p. 175 11. Chapter 11. Identifying the Genetic Basis for Human Disease - p. 203 12. Chapter 12. The Molecular Basis of Genetic Disease - p. 231 13. Chapter 13. The Molecular, Biochemical, and Cellular Basis of Genetic Disease - p. 251 14. Chapter 14. The Treatment of Genetic Disease - p. 293 15. Chapter 15. Developmental Genetics and Birth Defects - p. 321 16. Chapter 16. Cancer Genetics and Genomics - p. 347 17. Chapter 17. Genetic Counseling and Risk Assessment - p. 373 18. Chapter 18. Preconception and Prenatal Screening and Diagnosis - p. 391 19. Chapter 19. Application of Genomics to Medicine and Individualized Health Care - p. 411 20. Chapter 20. Ethical and Social Issues in Genetics and Genomics - p. 425 21. Clinical Case Studies Illustrating Genetic Principles - p. 435 22. Case Presentations - p. 435 23. 1. Abacavir-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (MIM 608579) (Genetically Determined Immunological Adverse Drug Reaction) - p. 435 24. 2. Achondroplasia (MIM 100800) (FGFR3 Pathogenic Variant) - p. 437 25. 3. Age-Related Macular Degeneration (MIM 603075) (Complement Factor H Variants) - p. 440 26. 4. Alzheimer Disease (MIM 104300) - p. 443 27. 5. 16p11.2 Deletion Syndrome (MIM 611913) - p. 446 28. 6. Beckwith-Wiedemann Syndrome (MIM 130650) (Uniparental Disomy and Imprinting Defect) - p. 449 29. 7. Hereditary Breast and Ovarian Cancer (MIM 604370, 612555) (BRCA1 and BRCA2 Pathogenic Variants) - p. 453 30. 8. Charcot-Marie-Tooth Disease Type 1 A (MIM 118220) (PMP22 Sequence Variant or Duplication) - p. 455 31. 9. CHARGE Syndrome (MIM 214800) (CHD7 Disorder) - p. 457 32. 10. Chronic Myelogenous Leukemia (MIM 608232) (BCR-ABL1 Oncogene) - p. 459 33. 11. Inflammatory Bowel Disease (MIM 266600) - p. 461 34. 12. Cystic Fibrosis (MIM 219700) (CFTR Pathogenic Variants) - p. 464 35. 13. Hearing Loss (NonSyndromic) (MIM 220290) (GJB2 Pathogenic Variants) - p. 469 36. 14. Duchenne Muscular Dystrophy (MIM 310200) (Dystrophin [DMD] Pathogenic Variants) - p. 471 37. 15. Monogenic Diabetes (MIM 600496) (Single Gene Pathogenic Variants Impacting Pancreatic Islet β Cell Development and/or Function) - p. 474 38. 16. Familial Hypercholesterolemia (MIM 143890) (Low-Density Lipoprotein Receptor [LDLR] Variants) - p. 478 39. Principles - p. 480 40. Major Phenotypic Features - p. 480 41. History and Physical Findings - p. 480 42. Background - p. 480 43. Questions for Small Group Discussion - p. 482 44. References - p. 482 45. 17. Fragile X Syndrome (MIM 300624), Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS) (MIM 300623), and Fragile X–Associated Primary Ovarian Insufficiency (FXPOI) (MIM 311360) (Pathogenic FMR1 Repeat Expansion) - p. 482 46. 18. GAUCHER DISEASE Type I (Non-Neuronopathic) (MIM 230800) (GBA Pathogenic Variants) - p. 486 47. 19. Glucose-6-Phosphate Dehydrogenase Deficiency (MIM 300908) (G6PD Pathogenic Variants) - p. 490 48. 20. Hereditary Hemochromatosis (MIM 235200) (HFE Pathogenic Variants) - p. 494 49. 21. Hemophilia (MIM 306700 and MIM 306900) (F8 or F9 Pathogenic Variants) - p. 497 50. 22. 22q11.2 Deletion Syndrome (MIM 188400 DiGeorge Syndrome or MIM 192430 Velocardiofacial Syndrome) - p. 500 51. 23. Holoprosencephaly (Nonsyndromic Form) (MIM 142945) (Sonic Hedgehog [SHH] variants) - p. 504 52. 24. Huntington Disease (MIM 143100) (HTT Pathogenic Variant [CAG Expansion]) - p. 508 53. 25. Hypertrophic Cardiomyopathy (MIM 192600) (Cardiac Sarcomere Gene Variants) - p. 512 54. 26. Proteus Syndrome (MIM 176920) (AKT1 Gene de novo Mosaic Variant) - p. 515 55. 27. Fetal Growth Restriction (Abnormal Fetal Karyotype) - p. 518 56. 28. Long QT Syndrome (MIM 192500) (Cardiac Ion Channel Gene) - p. 522 57. 29. Lynch Syndrome (MIM 120435) (DNA Mismatch Repair Genes Pathogenic Variants) - p. 526 58. 30. Marfan Syndrome (MIM 154700) (FBN1 Pathogenic Variants) - p. 529 59. 31. Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MIM 201450) (ACADM Pathogenic Variation) - p. 532 60. 32. Miller-Dieker Syndrome (MIM 247200) (17p13.3 Heterozygous Deletion) - p. 536 61. 33. Myoclonic Epilepsy With Ragged-Red Fibers (MIM 545000) (Mitochondrial tRNAlys Variant) - p. 540 62. Principles - p. 542 63. Major Phenotypic Features - p. 542 64. Case Report - p. 542 65. Background - p. 542 66. Phenotype and Natural History - p. 543 67. Management - p. 543 68. Inheritance - p. 543 69. Questions for Small Group Discussion - p. 543 70. References - p. 543 71. 34. Neurofibromatosis 1 (MIM 162200) (NF1 Pathogenic Variants) - p. 543 72. 35. Roifman Syndrome (MIM 616651) RNU4ATAC Noncoding RNA Gene Pathogenic Variants - p. 547 73. 36. Ornithine Transcarbamylase Deficiency (MIM 311250) (OTC Pathogenic Variant) - p. 550 74. 37. Polycystic Kidney Disease (MIM 173900 and MIM 613095) (PKD1 or PKD2 Pathogenic Variants) - p. 554 75. 38. Prader-Willi Syndrome (MIM 176270) (Absence of Paternally Derived 15q11-q13) - p. 558 76. 39. Retinoblastoma (MIM 180200) (RB1 Pathogenic Variants) - p. 563 77. 40. Rett Syndrome (MIM 312750) (MECP2 Variants) - p. 565 78. 41. Noonan Syndrome (RASopathies) (MIM 163950) - p. 567 79. 42. Sickle Cell Disease (MIM 603903) - p. 569 80. 43. Tay-TAY-Sachs Disease (MIM 272800) (HEXA Pathogenic Variants) - p. 571 81. 44. α-Thalassemia (α-Globin Deficiency) (MIM 604131) - p. 574 82. 45. Thiopurine S-Methyltransferase Deficiency (MIM 610460) (TPMT Variants) - p. 577 83. 46. Thrombophilia (MIM 188055 and 176860) (FV and PROC Pathogenic Variants) - p. 579 84. 47. Turner Syndrome (Female Monosomy X) Chromosomal - p. 583 85. 48. Xeroderma Pigmentosum (MIM 278700) (Defect of Nucleotide Excision Repair, XPA Pathogenic Variants) - p. 586 86. 49. Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure (MIM 614742) (TERT Pathogenic Variants) - p. 590 87. Glossary - p. 595 88. Index - p. 631
