Skip to main content
SpringerLink
Log in

Gene Action: Genetic Diseases

  • Chapter
Human Genetics

Abstract

Gene Action and Genetic Strategies. How do genes manage to determine the development and function of the organism? This is the basic problem of genetic biology that should be solved. The topics discussed earlier such as the structure of the genetic material and Mendelian segregation are interesting scientifically because they help in solving this basic question. In Chap.6 Mendelism is described as the central paradigm of genetics. Thus, a Mendelian mode of inheritance for a certain phenotype points to a specific change within the information-carrying DNA, and the study of linkage with DNA variants as markers leads to precise localization of the gene causing this phenotype. After the nature of the genetic alteration has been defined, the path of gene action between genotype and phenotype can be elucidated. For a long time linkage studies were known in principle to be the “King’s road” leading to gene localization. Linkage study in humans is more difficult than in experimental organisms because of the lack of directed matings. Although statistical techniques needed for human gene mapping have been available for some time, practical implementation was impeded by the lack of suitable genetic markers that could be used as landmarks for gene localization. This has fundamentally changed with discovery of the very frequent DNA polymorphisms. (Sect.12.1.2).

This investigation reveals... a clear case of a change produced in a protein molecule by an allelic change in a single gene involved in synthesis.

L. Pauling, “Sickle cell anemia, a molecular disease,” Science, 1949

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abel T, Maniatis T (1994) Mechanisms of eukaryotic gene regulation. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H (eds) The molecular basis of blood diseases, 2 nd edn. Saunders, Philadelphia, PP 33–70

    Google Scholar 

  2. Alargon B, Regueiro AA, Arnaiz-Villena A, Terhorst C (1988) Familial defect in the surface expression of the T-cell receptor–CD3 complex. N Engl J Med 319: 1203–1208

    Article  Google Scholar 

  3. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1983) Molecular biology of the cell. Garland, New York

    Google Scholar 

  4. Alter BP (1985) Antenatal diagnosis of thalassemia. a review. Ann N Y Acad Sci 445: 393–407

    Article  PubMed  CAS  Google Scholar 

  5. Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr 64: 146–148

    Google Scholar 

  6. Anderson DC, Smith CW, Springer TA (1989) Leucocyte adherence deficiency and other disorders of leucocyte motility. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2751–2778

    Google Scholar 

  7. Anderson WF (1992) Human gene therapy. Science 256: 808–813

    Article  PubMed  CAS  Google Scholar 

  8. Anonymous (1973) Pharmacogenetics. Report of a WHO scientific group. WHO Tech Rep Ser 524.

    Google Scholar 

  9. Anonymous (1978) Fetal haemoglobin in sickle-cell anaemia and thalassaemia–a clue to therapy? (Editorial). Lancet 1: 971–972

    Google Scholar 

  10. Anonymous (1988) Immunsystem, 2nd edn. Spektrum der Wissenschaft, Heidelberg

    Google Scholar 

  11. Anonymous (1993) Diagnosing the heart of the problem (Editorial). Nat Genet 4: 211–212

    Google Scholar 

  12. Antonarakis SE, Kazazian HH Jr, Orkin SH (1985) DNA polymorphism and molecular pathology of the human globin gene clusters. Hum Genet 69: 1–14

    Article  PubMed  CAS  Google Scholar 

  13. Baralle FE, Shoulders CC, Proundfoot NJ (1980) The primary structure of the human epsilon-globin gene. Cell 21: 621–626

    Article  PubMed  CAS  Google Scholar 

  14. Beadle GW (1945) Biochemical genetics. Chem Rev 37: 15–96

    Article  CAS  Google Scholar 

  15. Beadle GW, Ephrussi B (1936) The differentiation of eye pigments in drosophila as studied by transplantations.Genetics 21: 225–247

    CAS  Google Scholar 

  16. Beadle GW, Tatum EL (1941) Genetic control of biochemical reactions in neurospora. Proc Natl Acad Sci USA 27: 499–506

    Article  PubMed  CAS  Google Scholar 

  17. Becker MA, Kostel PJ, Meyer LJ, Seegmiller JE (1973) Human phosphoribosylpyrophosphate synthetase: increased enzyme specific activity in a family with gout and excessive purine synthesis. Proc Natl Acad Sci USA 70: 2749

    Article  PubMed  CAS  Google Scholar 

  18. Beet EA (1949) The genetics of the sickle cell trait in a Bantu tribe. Ann Eugen 14: 279

    PubMed  CAS  Google Scholar 

  19. Bell DA et al (1993) Genotype phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis 14: 1689–92

    Article  PubMed  CAS  Google Scholar 

  20. Bellingham AJ (1976) Haemoglobins with altered oxygen affinity. Br Med Bull 32: 234–238

    PubMed  CAS  Google Scholar 

  21. Benöhr HC, Waller HD (1975) Metabolism in haemolytic states. Clin Haematol 4: 45–62

    PubMed  Google Scholar 

  22. Benson MD (1995) Amyloidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease, vol 3, 7th edn. McGraw-Hill, New York, pp 4157–4191

    Google Scholar 

  23. Betke K, Beutler E, Brewer GJ, Kirkman HN, Luzzato L, Motulsky AG, Ramot B, Siniscalco M (1967) Standardization of procedures for the study of glucose-6-phosphate dehydrogenase. WHO Tech Rep Ser 366

    Google Scholar 

  24. Beutler E (1969) G-6-PD activity of individual erythrocytes and X-chromosomal inactivation. In: Yunis JJ (ed) Biochemical methods in red cell genetics. Academic, New York, pp 95–113

    Google Scholar 

  25. Beutler E (1975) Red cell metabolism. A manual of biochemical methods. Grune and Stratton, New York

    Google Scholar 

  26. Beutler E (1979) Review: Red cell enzyme defects as non-diseases and as diseases. Blood 54: 1–7

    PubMed  CAS  Google Scholar 

  27. Beutler E (1993) Gaucher disease as a paradigm of current issues regarding single gene mutations of humans. Proc Natl Acad Sci USA 90: 5384–5390

    Article  PubMed  CAS  Google Scholar 

  28. Beyreuther K, Multhaupt B, Masters CL (1996) Alzheimer Krankheit. Molekulare Pathogenese and deren Implikationen für die Therapieforschung. Akademie-Journal 2 95: 28–39

    Google Scholar 

  29. Bickel H (1953) Influence of phenylalanine intake on phenylketonuria. Lancet 2: 812

    Article  Google Scholar 

  30. Bickel Med Surg 12: 114–118 (1954)

    Google Scholar 

  31. Blackwell TK, Alt FW (1988) Immunoglobulin genes. In: Hames BD, Glover DM (eds) Molecular immunology. IRL, Oxford, pp 1–60

    Google Scholar 

  32. Blombäck M, Blombäck B, Mammen EF, Prasad AS (1968) Fibrinogen Detroit - a molecular defect in the N-terminal disulphide knot of human fibrinogen? Nature 218: 134

    Article  PubMed  Google Scholar 

  33. Bonaiti-Pellié C, Phung L, Nordmann Y (1984) Recurrence risk estimation of acute intermittent porphyria based on analysis of porphobilinogen deaminase activity: a Bayesian approach. Am J Med Genet 19: 755762

    Google Scholar 

  34. Bothwell TH, Charlton RW, Motulsky AG (1983) Idiopathic hemochromatosis. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1269–1298

    Google Scholar 

  35. Boyer SH, Rucknagel DL, Weatherall DJ, Watson-Williams EJ (1963) Further evidence for linkage between the 13 and S loci governing human hemoglobins and the population dynamics of linked genes. Am J Hum Genet 15: 438–448

    PubMed  CAS  Google Scholar 

  36. Bradley TB, Boyer SH, Allen FH (1961) Hopkins-2-hemoglobin: a revised pedigree with data on blood and serum groups. Bull Johns Hopkins Hosp 108: 75–79

    Google Scholar 

  37. Braunitzer G, Hilschmann N, Rudloff V, Hilse K, Liebold B, Müller R (1961) The haemoglobin particles. Chemical and genetic aspects of their structure. Nature 190: 480

    Google Scholar 

  38. Brewer GJ (1971) Annotation: human ecology, an expanding role for the human geneticist. Am J Hum Genet 23: 92–94

    PubMed  CAS  Google Scholar 

  39. Brown MS, Goldstein JL (1974) Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man. Science 185: 61–63

    Article  PubMed  CAS  Google Scholar 

  40. Brown MS, Goldstein JL (1976) New directions in human biochemical genetics: understanding the manifestations of receptor deficiency states. Prog Med Genet [New Ser] 1: 103–119

    CAS  Google Scholar 

  41. Brown MS, Goldstein JL (1984) How LDL receptors influence cholesterol and atherosclerosis. Sci Am 251: 5866

    Article  Google Scholar 

  42. Bunn HF (1994) Sickle hemoglobin and other hemoglobin mutants. In: Stamatoyannopoulos G, Nienhuis AW, Marjerus PW, Varmus H (eds) The molecular basis of blood diseases, 2nd edn. Saunders, Philadelphia, pp 207–256

    Google Scholar 

  43. Bunn HF, Forget BS, Ranney HM (1977) Human hemoglobins. Saunders, Philadelphia

    Google Scholar 

  44. Burnet FM (1959) The clonal selection theory of acquired immunity. Cambridge Universtiy Press, London

    Google Scholar 

  45. Butenandt A (1953) Biochemie der Gene und Genwirkungen. Naturwissenschaften 40: 91–100

    Article  CAS  Google Scholar 

  46. Byers PH (1989) Disorders of collagen biosynthesis and structure. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2805–2842

    Google Scholar 

  47. Byers PH (1990) Brittle bones–fragile molecules: disorders of collagen structure and expression. Trends Genet 6: 293–300

    Article  PubMed  CAS  Google Scholar 

  48. Byers PH, Tsipouras P, Bonadio JF et al (1988) Perinatal lethal osteogenesis imperfecta (0I type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet 42: 237–248

    PubMed  CAS  Google Scholar 

  49. Byers PH, Wallis GA, Willing MC (1991) Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet 28: 433–442

    Article  PubMed  CAS  Google Scholar 

  50. Lantz M, Gehler J (1976) The mucopolysaccharidoses: Inborn errors of glycosaminoglycan catabolism. Hum Genet 32: 233–255

    Google Scholar 

  51. Cao A (1994) 1993 William Allan award address. Am J Hum Genet 54: 397–402

    Google Scholar 

  52. Cao A, Cossu P, Falchi AM, Monni G, Pirastu M, Rosatelli C, Scalas MT, Tuveri T (1985) Antenatal diagnosis of thalassemia major in Sardinia. Ann N Y Acad Sci 445: 380–392

    Article  PubMed  CAS  Google Scholar 

  53. Carrier L, Hengstenberg C, Beckmann JS et al (1993) Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome n. Nat Genet 4: 311–313

    Article  PubMed  CAS  Google Scholar 

  54. Carson PE, Flanagan CL, Ickes CE, Alving AS (1956) Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124: 484–485

    Article  PubMed  CAS  Google Scholar 

  55. Carver MFH, Cutler A (1994) International hemoglobin information center variant list. Hemoglobin 18: 77161

    Google Scholar 

  56. Childs B, Zinkham W (1958) A genetic study of a defect in glutathione metabolism of the erythrocyte. Johns Hopkins Med J 102: 21–37

    CAS  Google Scholar 

  57. Cholerton S, Daly AK, Idle JR (1992) The role of individual human cytochromes P45o in drug metabolism and clinical response. Trends Pharmacol Sci 13: 434–439

    Article  PubMed  CAS  Google Scholar 

  58. Chuang DT, Fisher CW, Lau KS et al (1991) Maple syrup urine disease; domain structure, mutations and exon skipping in the dihydrolipoyl transacylase ( E2) component of the branced-chain alpha keto acid dehydrogenase complex. Mol Biol Med 8: 49–63

    Google Scholar 

  59. Chung D, Ichinose A (1989) Hereditary disorders related to fibrinogen and factor XIII. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2135–2153

    Google Scholar 

  60. Cleaver JE (1972) Xeroderma pigmentosum: Variants with normal DNA repair and normal sensitivity to ultraviolet light. J Invest Dermatol 58: 124–128

    Article  PubMed  CAS  Google Scholar 

  61. Clevers H, Alarcon B, Wileman T, Terhorst C (1988) The T cell receptor CD 3 complex: a dynamic protein ensemble. Annu Rev Immunol 6: 629–662

    Article  PubMed  CAS  Google Scholar 

  62. Collinge J, Poulter M, Davis MB et al (1991) Presymptomatic detection or exclusion of prion protein gene defects in families with inherited prion diseases. Am J Hum Genet 49: 1351–1354

    PubMed  CAS  Google Scholar 

  63. Collins FS, Weissman SM (1984) The molecular genetics of human hemoglobins nucleic acid. Res Mol Biol 31: 315–462

    CAS  Google Scholar 

  64. Cooper DN, Krawczak M (1993) Human gene mutation. Bioscience Scientific, Oxford

    Google Scholar 

  65. Cori GT, Cori CF (1952) Glucose-6-phosphatase of the liver in glycogen storage disease. J Biol Chem 199: 661

    PubMed  CAS  Google Scholar 

  66. Costa T, Scriver CR, Childs B (1985) The effect of Mendelian disease on human health: a measurement. Am J Med Genet 21: 231–242

    Article  PubMed  CAS  Google Scholar 

  67. Cox DW (1995) Alpha-i-antitrypsine deficiency. In: The metabolic and molecular basis of inherited disease, 7th edn. McGraw-Hill, New York, pp 4125–4158

    Google Scholar 

  68. Dacie JV, Mollison PL, Richardson N, Selwyn JG, Shapiro L (1953) Atypical congenital haemolytic anemia. Q J Med 22: 79

    PubMed  CAS  Google Scholar 

  69. De Vries DD, de Wijs IJ, Wolff G et al (1993) X-linked myoclonus epilepsy explained as a maternally inherited mitochondrial disorder. Hum Genet 91: 51–54

    Article  PubMed  Google Scholar 

  70. Desnick RJ (ed) (1980) Enzyme therapy in genetic diseases. Liss, New York

    Google Scholar 

  71. Desnick RJ (ed) (1991) Treatment of genetic diseases. Churchill Livingstone, New York

    Google Scholar 

  72. Driscoll MC, Dobkin CS, Alter BP (1989) ad13-thalessemia due to a de novo mutation deleting the 5’ (3-globin gene activation-region hypersensitive sites. Proc Natl Acad Sci USA 86: 7470

    Google Scholar 

  73. Eichelbaum M, Gross AS (1991) The genetic polymorphism of debrisoquine sparteine metabolism–clinical aspects. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Elsevier, Amsterdam, pp 625–648

    Google Scholar 

  74. Emery AEH, Anand R, Danford N, Duncan W, Paton L (1978) Aryl-hydrocarbon-hydroxylase inducibility in patients with cancer. Lancet 1: 470–472

    Article  PubMed  CAS  Google Scholar 

  75. Epstein CJ (1977) Inferring from modes of inheritance to the mechanisms of genetic disease. In: Rowland LP (ed) Pathogenesis of human muscular dystrophies. Excerpta Medica, Amsterdam, pp 9–22

    Google Scholar 

  76. Evans DAP (1993) The debrisoquine sparteine polymorphism (cytochrome P450 2D6). In: Price Evans DA (ed) Genetic factors in drug therapy. Cambridge University Press, Cambridge, pp 54–88

    Google Scholar 

  77. Evans DAP (1993) N-Acetyltransferase. In: Genetic factors in drug therapy. Cambridge University Press, Cambridge, pp 211–302

    Google Scholar 

  78. Evans DAP (1993) Genetic factors in drug therapy. Cambridge University Press, Cambridge, pp 137–175

    Google Scholar 

  79. Evans DAP, Manley K, McKusick VA (1960) Genetic control of isoniazid metabolism in man. BMJ 2: 485

    Google Scholar 

  80. Fisher CR, Fisher CW, Chuang DT, Cox RP (1991) Occurrence of a tyr393-to-asn (Y393N) mutation in the El-alpha gene of the branced-chain alpha-ketoacid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population. Am J Hum Genet 49: 429–434

    PubMed  CAS  Google Scholar 

  81. Fisher CW, Lau KS, Fisher CR et al (1991) A 17 bp insertion and a phe 215-to-cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34. Biochem Biophys Res Commun 174: 804–809

    Article  PubMed  CAS  Google Scholar 

  82. Flatz G (1971) Population study of erythrocyte glutathione reductase activity. II. Hematological data of subjects with low enzyme activity and stimulation characteristics in their families. Hum Genet 11: 278–285

    Article  CAS  Google Scholar 

  83. Flatz G (1971) Population study of erythrocyte glutathione reductase activity I. Stimulation of the enzyme by flavin adenine dinucleotide and by riboflavin substitution. Hum Genet 11: 269–277

    Article  CAS  Google Scholar 

  84. Flatz G (1992) Lactase deficiency: biological and medical aspects of the adult human lactase polymorphism. In: King RA, Rotter JI, Motulsky AG (eds) The genetic basis of common disease. Oxford University Press, New York, pp 305–325

    Google Scholar 

  85. Flatz G, Xirotiris N (1976) Glukose-6-phosphat-dehydrogenase. In: Becker PE (ed) Humangenetik, ein kurzes Handbuch, vol 3. Thieme, Stuttgart, pp 494–535

    Google Scholar 

  86. Flint J, Harding RM, Clegg JB, Boyce AJ (1993) Why are some genetic disorders common? Distinguishing selection from other processes by molecular analysis of globin gene variants. Hum Genet 91: 91–117

    Article  PubMed  CAS  Google Scholar 

  87. Foiling A (1934) Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität. Hoppe Seylers Z Physiol Chem 227: 169

    Article  Google Scholar 

  88. Forbes GB (1953) Glycogen storage disease. J Pediatr 42: 645

    Article  PubMed  CAS  Google Scholar 

  89. Forrester WC, Thompson C, Elder JT, Goudine M (1986) A developmentally stable chromatin structure in the human 13-globin cluster. Proc Natl Acad Sci USA 83: 1359

    Article  PubMed  CAS  Google Scholar 

  90. Franceschetti A, Klein D (1954) Le dépistage des hétérozygotes. In: Gedda L (ed) Genetica medica. Orrizonte Medico, Rome

    Google Scholar 

  91. Fratantoni JC, Hall CW, Neufeld EF (1968) Hunter and Hurler syndromes. Mutual correction of the defect in cultured fibroblasts. Science 162: 570–572

    Google Scholar 

  92. Friedmann T, Seegmiller JE, Subak-Sharpe JH (1968) Metabolic cooperation between genetically marked human fibroblasts in tissue culture. Nature 220: 272–274

    Article  CAS  Google Scholar 

  93. Frézal J, Munnich A, Mitchell G (1983) One gene, several messages. From multifunctional proteins to endogenous opiates. Hum Genet 64: 311–314

    Google Scholar 

  94. Friedmann T (1989) Progress toward human gene therapy. Science 244: 1275–1282

    Article  PubMed  CAS  Google Scholar 

  95. Fujii J, Zorzato F, De Leon S, Khanna VK, Weiler JE, O’Brien PJ, MacLennan DH (1991) Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253: 448

    Article  PubMed  CAS  Google Scholar 

  96. Garrod AE (1902) The incidence of alcaptonuria: a study in chemical individuality. Lancet 2: 1616–1620

    Article  CAS  Google Scholar 

  97. Garrod AE (1923) Inborn errors of metabolism. Frowde, London (Reprint 1963 Oxford University Press, London )

    Google Scholar 

  98. Geisterfer-Lowrance AAT, Kass S, Sasazuki T et al (1990) A molecular basis for familiar hypertrophic cardiomyopathy: a ß cardiac myosin heavy chain gene missense mutation. Cell 62: 999–1006

    Article  PubMed  CAS  Google Scholar 

  99. Gibbons RJ, Wilkie AOM, Weatherall DJ, Higgs DR (1991) A newly defined x-linked mental retardation syndrome associated with a-thalassemia. J Med Genet 28: 729

    Article  PubMed  CAS  Google Scholar 

  100. Gibson QH (1948) The reduction of methaemoglobin in red blood cells and studies on the cause of idiopathic methaemoglobinaemia. Biochem J 42: 13–23

    PubMed  CAS  Google Scholar 

  101. Gibson QH, Harrison DC (1947) Familial idiopathic methemoglobinemia. Lancet 2: 941–943

    Article  PubMed  CAS  Google Scholar 

  102. Glatt H, Oesch F (1984) Variations in epoxide hydro-last activities in human liver and blood. In: Omenn GS, Gelboin HV (eds) Genetic variability in responses to chemical exposure. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 189–2o1(CHS Banbury report 16 )

    Google Scholar 

  103. Goldfarb LG, Petersen RB, Tabatan M et al (1992) Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science 258: 806–808

    Article  PubMed  CAS  Google Scholar 

  104. Goldschmidt RB (1935) Gen and Außeneigenschaft (Untersuchungen an Drosophila) I. and II. Mitt Z Vererbungslehre 10: 74–98

    Google Scholar 

  105. Goldstein JL, Brown MS (1977) The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46: 897–930

    Article  PubMed  CAS  Google Scholar 

  106. Goldstein JL, Brown MS (1989) In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York

    Google Scholar 

  107. Graham JB, Barrow ES, Reisner HM, Edgell CJS (1983) The genetics of blood coagulation. Adv Hum Genet 13: 1–81

    Article  PubMed  CAS  Google Scholar 

  108. Grove DI, Forbes IJ (1975) Increased resistance to helminth infestation in an atopic population. Med J Aust 1: 336–338

    PubMed  CAS  Google Scholar 

  109. Guthrie R, Susi A (1963) A simple phenylalanine method for detecting phenylketonuria in large populations of newborns. Pediatrics 32: 338

    PubMed  CAS  Google Scholar 

  110. Haldane JBS (1954) The biochemistry of genetics. London

    Google Scholar 

  111. Harris H (1980) The principles of human biochemical genetics, 4th edn. North-Holland, Amsterdam in. Hayashi A, Fujita T, Fujimura M, Titani K (1980) A new abnormal fetal hemoglobin, Hb FM Osaka (a„ az 63 HIS’ Tyr). Hemoglobin 4: 447

    Google Scholar 

  112. Heckbert SR, Weiss NS, Hornung SK, Eaton DL, Motulsky AG (1992) Glutathione S-transferase and epoxide hydrolase activity in human leukocytes in relation to the risk of lung and other smoking-related cancers. J Natl Cancer Inst 84: 414–422

    Article  PubMed  CAS  Google Scholar 

  113. Hentze MW (1991) Determinants and regulation of cytoplasmic mRNA stability in eukaryotic cells. Biochim Biophys Acta 1090: 281–292

    Article  PubMed  CAS  Google Scholar 

  114. Herrick JB (1910) Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med 6: 517

    Article  Google Scholar 

  115. Higgs DR, Hill AVS, Micholls R, Goodbourn SEY, Ayyub H, Teal H, Clegg JB, Weatherall DJ (1985) Molecular rearrangements of the human a-gene cluster. Ann N Y Acad Sci 445: 45–56

    Article  PubMed  CAS  Google Scholar 

  116. Hilschmann N, Craig LC (1965) Amino acid sequence studies with Bence-Jones proteins. Proc. Natl Acad Sci USA 53: 1403

    Google Scholar 

  117. Hilschmann N, Kratzin H, Altevogt P, Ruban E, Kortt A, Staroscik C, Scholz R, Palm W, Barnikol H-U, Barnikol-Watanabe S, Bertram J, Horn J, Engelhard M, Schneider M, Dreher W (1976) Evolutionary origin of antibody specificity. In: Goodman M, Tashian RE (eds) Molecular anthropology. Plenum, New York, pp 369–386

    Chapter  Google Scholar 

  118. Hobbs HH, Russell DW, Brown GS, Goldstein JL (1990) The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu Rev Genet 24: 133–170

    Article  PubMed  CAS  Google Scholar 

  119. Honig GR, Adams JG III (1986) Human hemoglobin genetics. Springer, Vienna

    Google Scholar 

  120. Hörlein H, Weber G (1948) Über chronische familiäre Methämoglobinämie and eine neue Modifikation des Methämoglobins. Dtsch Med Wochenschr 72: 476

    Article  Google Scholar 

  121. Howell DR, Williams JC (1983) The glycogen storage diseases. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 141–166

    Google Scholar 

  122. Huisman THJ, Wilson JB, Gravely M, Hubbard M (1974) Hemoglobin grady: the first example of a variant with elongated chains due to an insertion of residues. Proc Natl Acad Sci USA 71: 3270–3273

    Article  PubMed  CAS  Google Scholar 

  123. Ingram VM (1956) A specific chemical difference between the globins of normal human and sickle cell anaemia haemoglobin. Nature 178: 792

    Article  PubMed  CAS  Google Scholar 

  124. Jackson LG (1985) First-trimester diagnosis of fetal genetic disorders. Hosp Pract 20: 39–48

    CAS  Google Scholar 

  125. Jaenicke T, Diederich KW, Haas Wet al (1990) The complete sequence of the human (3-myosin heavy chain gene and a comperative analysis of its product. Genomics 8: 194–206

    Google Scholar 

  126. Jandl JH, Cooper RA (1978) Hereditary spherocytosis. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw-Hill, New York, pp 1396–1409

    Google Scholar 

  127. Jervis GA (1953) Phenylpyruvic oligophrenia: deficiency of phenylalanine oxidizing system. Proc Soc Exp Biol Med 82: 514–515

    PubMed  CAS  Google Scholar 

  128. Kahn A, Kaplan J-C, Dreyfus J-C (1979) Advances in hereditary red cell enzyme anomalies. Hum Genet 50: 1–27

    Article  PubMed  CAS  Google Scholar 

  129. Kainulainen K, Pulkkinen L, Savolainen AC et al (1990) Location on chromosome 15 of the genetic defect causing Marfan syndrome. N Engl J Med 323: 935–939

    Article  PubMed  CAS  Google Scholar 

  130. Kainulainen K, Steinmann B, Collins F et al (1991) Mar-fan syndrome: no evidence for heterogeneity in different populations, and more precise mapping of the gene. Am J Hum Genet 49: 662–667

    PubMed  CAS  Google Scholar 

  131. Kalckar HM (1957) Biochemical mutations in man and microorganisms. Science 125: 105–108

    Article  PubMed  CAS  Google Scholar 

  132. Kalow W, Grant DM (1995) Pharmacogenetics. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease, vol 3, 7th edn. McGraw-Hill, New York, pp 293–326

    Google Scholar 

  133. Kalow W, Staron N (1957) On distribution and inheritance of human serum cholinesterase, as indicated by dibucaine numbers. Can J Biochem 35: 1305

    Article  PubMed  CAS  Google Scholar 

  134. Kamuzora H, Lehmann H (1975) Human embryonic haemoglobins including a comparison by homology of the human and Cl chains. Nature 256: 511–513

    Article  PubMed  CAS  Google Scholar 

  135. Kan YW (1985) Molecular pathology of a-thalassemia. Ann N Y Acad Sci 445: 28–35

    Article  PubMed  CAS  Google Scholar 

  136. Kan YW, Chang JC, Poon R (1979) Nucleotide sequences of the untranslated 5’ and 3’ regions of human a-, (3- and y-globin mRNAs. In: Stamatoyannopoulos G, Nienhuis A (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton, New York, pp 595–606

    Google Scholar 

  137. Kazazian HH (1990) The thalassemia syndromes: molecular basis and prenatal diagnosis in 1990. Semin Hema-tol 27: 209

    CAS  Google Scholar 

  138. Kellermann G, Luyten-Kellerman M, Shaw CR (1973) Genetic variation of aryl hydrocarbon hydroxylase in human lymphocytes. Am J Hum Genet 25: 327–331

    PubMed  CAS  Google Scholar 

  139. Kellermann G, Shaw CR, Luyten-Kellerman M (1973) Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma. N Engl J Med 289: 934

    Article  PubMed  CAS  Google Scholar 

  140. Kelley WN, Greene ML, Rosenbloom FM, Henderson JF, Seegmiller JE (1969) Hypoxanthine-guanine phosphoribosyl transferase in gout. Ann Intern Med 70: 155–206

    PubMed  CAS  Google Scholar 

  141. Kelly WJ, Wyngaarden JB (1983) Clinical syndromes associated with HPRT deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1115–1143

    Google Scholar 

  142. Kendrew JC, Dickerson RE, Strandberg BE, Hart RG, Davies DR, Phillips DC, Shore VC (1960) Structure of myoglobin - a three-dimensional Fourier synthesis at 2 A. Resolution. Nature 185: 422–427

    Google Scholar 

  143. Kessel M, Gruss P (1990) Murine developmental control genes. Science 249: 375–379

    Article  Google Scholar 

  144. Kirkman HN (1972) Enzyme defects. Prog Med Genet 8: 125–168

    CAS  Google Scholar 

  145. Kresse H, Cantz M, von Figura K, Glössl J, Paschke E (1981) The mucopolysaccharidoses: biochemistry and clinical symptoms. Klin Wochenschr 59: 867–876

    Article  PubMed  CAS  Google Scholar 

  146. Krooth RS, Weinberg AN (1961) Studies on cell lines developed from the tissues of patients with galactosemia. J Exp Med 133: 1155–1171

    Article  Google Scholar 

  147. Kühn A (1961) Grundriß der Vererbungslehre. Quelle and Meyer, Heidelberg

    Google Scholar 

  148. Lee EJD, Zhao B, Moochhala SM, Ngoi SS (1994) Frequency of mutant CYPIAI, NAT2 and GSTM1 alleles in a normal Chinese population. Pharmacogenetics 4: 355–358

    Article  PubMed  CAS  Google Scholar 

  149. Lehmann H, Huntsman RG (1974) Man’s hemoglobins. North-Holland, Amsterdam

    Google Scholar 

  150. Lehmann H, Ryan E (1956) The familial incidence of low pseudocholinesterase level. Lancet 2: 124

    Article  Google Scholar 

  151. Lenke RR, Levy HL (1980) Maternal phenylketonuria and hyperphenylalaninemia: an international survey of the outcome of untreated and treated pregnancies. N Engl J Med 303: 1202

    Article  PubMed  CAS  Google Scholar 

  152. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36: 561

    Article  PubMed  CAS  Google Scholar 

  153. Liebhaber SA, Goossens MJ, Kan YW (1980) Cloning and complete sequence of human 5’-alpha-globin gene. Proc Natl Acad Sci USA 77: 7054–7058

    Article  PubMed  CAS  Google Scholar 

  154. Lin HJ, Han CY, Lin BK, Hardy S (1993) Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, Blacks, Hispanics and Whites: application to metabolic epidemiology. Am J Hum Genet 52: 827–834

    PubMed  CAS  Google Scholar 

  155. Llerna A, Edman G, Cobaleda J, Ben’itez J, Schalling D, Bertilsson L (1993) Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuractive substrate of product of the cytochrome P4502D6. Acta Psychiatr Scand 87: 23–28

    Article  Google Scholar 

  156. Loh EY, Covirla SC, Serafini AT et al (1988) Human Tcell-receptor 8-chain: genomic organization, diversity and expression in populations of cells. Proc Natl Acad Sci USA 85: 9714–9718

    Article  PubMed  CAS  Google Scholar 

  157. London SJ, Daly AK, Thomas DC, Caporaso NE, Idle JR (1994) Methodological issues in the interpretation of studies of the CYP2D6 genotype in relation to lung cancer risk. Pharmacogenetics 4: 107–108

    Article  PubMed  CAS  Google Scholar 

  158. Lux SE, Becker PS (1989) Disorders of the red cell membrane skeleton: hereditary pherocytosis and hereditary elliptocytosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis inherited disease, 6th edn. McGraw-Hill, New York, pp 2367–2408

    Google Scholar 

  159. Marrack P, Kappler J (1987) The T cell receptor. Science 238: 1073–1079

    Article  PubMed  CAS  Google Scholar 

  160. Martinez J, Holburn RR, Shapiro S, Erslev AJ (1974) Fibrinogen Philadelphia: a hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism. J Clin Invest 53: 600

    Article  PubMed  CAS  Google Scholar 

  161. Masirimiriembwa CM, Johannson I, Hasler JA, Ingelman-Sundberg M (1993) Genetic polymorphism of cytochrome P450 CYP2D6 in Zimbabwean population. Pharmacogenetics 3: 275–280

    Article  Google Scholar 

  162. a. Masters CL, Beyreuther K, Trillet M, Christen Y (eds) (1994) Amyloid protein precursor in development, aging, and Alzheimer’s disease. Springer, Berlin Heidelberg New York

    Google Scholar 

  163. May A, Huehns ER (1976) The mechanism and prevention of sickling. Br Med Bull 32: 223–233

    PubMed  CAS  Google Scholar 

  164. McKusick VA (1972) Heritable disorders of connective tissue, 4th edn. Mosby, St Louis

    Google Scholar 

  165. McKusick VA (1995) Mendelian inheritance in man, 11th edn. Johns Hopkins University Press, Baltimore

    Google Scholar 

  166. Meyer UA, Skoda RC, Zanger UM, Heim M, Broly F (1992) The genetic polymorphism of debrisoquine sparteine metabolism–molecular mechanisms. In: Pharmacogenetics of drug metabolism. Elsevier, Amsterdam, pp 609–624

    Google Scholar 

  167. Meyers DA, Marsh DG (1992) Allergy and asthma. In: King RA, Rotter JI, Motulsky AG (eds) The genetic basis of common disease. Oxford University Press, New York, pp 130–149

    Google Scholar 

  168. Miller AD (1992) Human gene therapy comes of age. Nature 357: 455–460

    Article  PubMed  CAS  Google Scholar 

  169. Motulsky AG (1957) Drug reactions, enzymes and biochemical genetics. JAMA 165: 835–837

    Google Scholar 

  170. Motulsky AG (1965) Theoretical and clinical problems of glucose-6-phosphate dehydrogenase deficiency. In: Jon-xis JHP (ed) Abnormal haemoglobins in Africa. Blackwell, Oxford, pp 143–196 a

    Google Scholar 

  171. Motulsky AG (1970) Biochemical genetics of hemoglobins and enzymes as a model for birth defect research. In: Frazer FC, McKusick VA (eds) Congenital malformations. Excerpta Medica, Amsterdam, p 199

    Google Scholar 

  172. Motulsky AG (1972) Hemolysis in glucose-6-phosphate dehydrogenase deficiency. Fed Proc 31: 1286–1292

    PubMed  CAS  Google Scholar 

  173. Motulsky AG (1973) Frequency of sickling disorders in US blacks. N Engl J Med 288: 31–33

    Article  PubMed  CAS  Google Scholar 

  174. Motulsky AG (1975) Glucose-6-phosphate dehydrogenase and abnormal hemoglobin polymorphisms–evidence regarding malarial selection. In• Salzano FM (ed) The role of natural selection in human evolution. North-Holland, Amsterdam, pp 271–291

    Google Scholar 

  175. Motulsky AG (1977) Ecogenetics: genetic variation in susceptibility to environmental agents. In: Human genetics. Proceedings of the 5th International Congress of Human Genetics, Mexico City, 10–15 Oct 1976. Excerpta Medica, Amsterdam, pp 375–385

    Google Scholar 

  176. Motulsky AG (1978) Multifactorial inheritance and heritability in pharmacogenetics. International Titisee Conference, Titisee, 13–15 Oct 1977. Hum Genet 1 [Suppl]: 7–12

    Google Scholar 

  177. a. Motulsky AG (1995) Jewish diseases and origins. News and views. Nature [Genet] 9: 99–101

    Google Scholar 

  178. b. Motulsky AG (1996) Nutritional ecogenetics: homocysteine-related arterioclerotic vascular disease, neural tube defects, and folic acid ( Invited editorial ). Am J Hum Genet 58: 17–20

    Google Scholar 

  179. c. Motulsky AG (1996) Human genetic variation in nutrition and chronic disease prevention. 3rd International Symposium on Infant Nutrition in the Prevention of Chronic Pathology, Sept 18–22, 1995, Alicante. Ergon, Madrid (in press)

    Google Scholar 

  180. Motulsky AG, Vogel F, Buselmaier W, Reichert W, Kellermann G, Berg P (eds) (1978) Human genetic variation in response to medical and environmental agents: pharmacogenetics and ecogenetics. International Titisee Conference, Titisee, 13–15 Oct 1977. Hum Genet 1 [Suppl]

    Google Scholar 

  181. Mueller RF, Hornung S, Furlong CE, Anderson J, Giblett ER, Motulsky AG (1983) Plasma paraoxonase polymorphism: a new enzyme assay, population, family, biochemical, and linkage studies. Am J Hum Genet 35: 393408

    Google Scholar 

  182. Mullan M, Crawford F (1993) Genetic and molecular advances in Alzheimer’s disease. Trends Neurosci 16: 398403

    Google Scholar 

  183. Nagel RL, Labie D (1985) The consequences and implications of the multicentric origin of the Hb S gene. In: Stamatoyannopoulos G, Nienhuis A (eds) Experimental approaches for the study of hemoglobin switching. Liss, New York, pp 93–103

    Google Scholar 

  184. Nazar-Stewart V, Motulsky AG, Eaton DL, White E, Hornung SK, Leng Z-T, Stapleton P, Weiss NS (1993) The glutathione S-transferase Mu polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res 53: 2313–2318

    PubMed  CAS  Google Scholar 

  185. Nebert DW, Goujon FM, Gielen JE (1972) Aryl hydrocarbon hydroxylase induction by polycyclic hydrocarbons: Simple autosomal dominant trait in the mouse. Nature [New Biol] 236: 107

    Google Scholar 

  186. Neel JV (1949) The inheritance of sickle cell anemia. Science 110: 64

    Article  PubMed  CAS  Google Scholar 

  187. Neel JV (1949) The detection of the genetic carriers of hereditary disease. Am J Hum Genet 1 2: 19–36

    PubMed  CAS  Google Scholar 

  188. Neel JV (1953) The detection of the genetic carriers of inherited disease. In: Sorsby A (ed) Clinical genetics. Mosby, St Louis, p 27

    Google Scholar 

  189. Nienhuis AW, Anagnou NP, Ley TJ (1984) Advances in thalassemia research. Blood 63: 738–758

    PubMed  CAS  Google Scholar 

  190. Neufeld EF (1974) The biochemical basis for mucopolysaccharidoses and mucolipidoses. Prog Med Genet 10: 81-loi

    Google Scholar 

  191. Neufeld EF, Muenzer J (1989) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6 th edn. McGraw-Hill, New York, pp 1565–1587

    Google Scholar 

  192. Newton BW, Benson RC, McCarriston CC (1966) Sparteine sulphate: a potent carpicious oxytocic. Am J Obstet Gynecol 94: 234–241

    PubMed  CAS  Google Scholar 

  193. Oettinger MA, Schatz DG, Gorka C, Baltimore D (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248: 1517–1523

    Article  PubMed  CAS  Google Scholar 

  194. Old JM (1992) Haemoglobinopathies. In: Brock DH (ed) Prenatal diagnosis and screening. Churchill, London, pp 425–439

    Google Scholar 

  195. Old JM, Weatherall DJ, Wart RHT, Petrou M, Modell B, Rodeck CH, Warren R, Morsman JM (1985) First trimester diagnosis of the hemoblobin disorders. Ann N Y Acad Sci 445: 349–356

    Article  PubMed  CAS  Google Scholar 

  196. Omenn GS, Motulsky AG (1978) “Ecogenetics”: genetic variation in susceptibility to environmental agents. In: Cohen BH, Lilienfeld AM, Huang PC (eds) Genetic issues in public health and medicine. Thomas, Springfield, pp 83–111

    Chapter  Google Scholar 

  197. Orkin SH, Kazazian HH Jr (1984) The mutation and polymorphism of the human [3- globin gene and its surrounding area. Annu Rev Genet 18: 131–171

    Article  PubMed  CAS  Google Scholar 

  198. Orkin SH, Motulsky AG (1995) Report and recommendation of the Panel to Assess the NIH Investment in Research on Gene Therapy. National Institutes of Health, Bethesda

    Google Scholar 

  199. Orkin SH, Alter BP, Itay C, Mahoney MJ, Lazarus H, Hobbins JC, Nathan DG (1978) Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med 299: 166–172

    Article  PubMed  CAS  Google Scholar 

  200. Pauling L, Itano HA, Singer SJ, Wells IC (1949) Sickle cell anemia: a molecualr disease. Science 110: 543

    Article  PubMed  CAS  Google Scholar 

  201. Penrose LS (1935) Inheritance of phenylpyruvic amentia (Phenylketonuria) Lancet 2: 192–194

    Article  Google Scholar 

  202. Perutz MF (1976) Structure and mechanism of haemoglobin. Br Med Bull 32: 195–208

    PubMed  CAS  Google Scholar 

  203. Prins HK, Oort M, Loos JA, Zürcher C, Beckers T (1966) Congenital nonspherocytic hemolytic anemia associated with glutathione deficiency of the erythrocytes. Blood 27: 145

    PubMed  CAS  Google Scholar 

  204. Propping P (1978) Pharmacogenetics Rev Physiol Biochem Pharmacol 83: 124–173

    Google Scholar 

  205. Propping P (1984) Genetic aspects of neurotoxicity. In: Blum K, Manzo L (eds) Neurotoxicology. Dekker, New York, pp 203–218

    Google Scholar 

  206. Propping P (1989) Psychiatrische Genetik. Springer, Berlin Heidelberg New York

    Book  Google Scholar 

  207. Pumphrey RSH (1986) Computer models of the human immunoglobulins. Immunol Today 7: 206-

    Google Scholar 

  208. Romeo G (1977) Analytical review. Enzymatic defects of hereditary porphyrias: an explanation of dominance at the molecular level. Hum Genet 39: 261–276

    Article  PubMed  CAS  Google Scholar 

  209. Romeo L, Osorio-Almeida L, Higgs DR et al (1991) aglobin structural genes. Blood 78: 1589–1595

    Google Scholar 

  210. Rommens JM, Ianuzzi MC, Kerem B-S et al (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245: 1059–1065

    Article  PubMed  CAS  Google Scholar 

  211. Rosenthal D, Kety SS (1968) The transmission of schizophrenia. Pergamon, Oxford

    Google Scholar 

  212. Sakai LY, Keene DR, Engvall E (1986) Fibrillin, a new 350 kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol 103: 2499–2509

    Article  PubMed  CAS  Google Scholar 

  213. Sandhoff K, Christomanou H (1979) Biochemistry and genetics of gangliosidoses. Hum Genet 50: 107–143

    Article  PubMed  CAS  Google Scholar 

  214. Schimpl A (1991) Antikörper and Antikörpersynthese. In: Gemsa D et al (eds) Immunologie, 3rd edn. Thieme, Stuttgart, pp 16–29

    Google Scholar 

  215. Schloot W, Goedde HW (1974) Biochemische Genetik des Menschen. In: Vogel F (ed) Erbgefüge. Springer, Berlin Heidelberg New York, pp 325–494 (Handbuch der allgemeinen Pathologie, vol 9 )

    Google Scholar 

  216. Schroeder WA, Huisman THJ (1978) Human gamma chains: structural features. In: Stamatoyannopoulos G, Nienhuis A (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton, New York,pp 29–45

    Google Scholar 

  217. Scriver CR (1969) Treatment of inherited disease: Realized and potential. Med Clin North Am 53: 941–963

    PubMed  CAS  Google Scholar 

  218. Scriver CR, Clow CL (1980) Phenylketonuria and other phenylalanine hydroxylase mutants in man. Annu Rev Genet 14: 179–202

    Article  PubMed  CAS  Google Scholar 

  219. Scriver CR, Rosenberg LE (1973) Amino acid metabolism and its disorders. Saunders, Philadelphia

    Google Scholar 

  220. Scriver CR, Beaudet AL, Sly WS, Valle D (eds) (1989) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York

    Google Scholar 

  221. Sears DA (1978) The morbidity of sickle cell trait. A review of the literature. Am J Med 64: 1021–1036

    Article  PubMed  CAS  Google Scholar 

  222. Seegmiller JE (1983) Disorders of purine and pyrimidine metabolism. In: Emery AEH, Rimoin DL (eds) Principles and practice of medical genetics. Churchill Livingstone, Edinburgh, pp 1286–1305

    Google Scholar 

  223. Seegmiller JE, Rosenbaum FM, Kelly WN (1967) An enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155: 1682

    Google Scholar 

  224. Seidegâard J, Pero RW, Markowitz MM, Roush G, Miller DG, Beattie EJ (1990) Isoenzymes(s) of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow-up study. Carcinogenesis u: 33–36

    Google Scholar 

  225. Semenza G (1981) Intestinal oligo-and disaccharides. In: Randle PJ, Steiner DF, Whelan WJ (eds) Carbohydrate metabolism and its disorders, vol 3. Academic, London, pp 425–479

    Google Scholar 

  226. Serjeant GR (1974) The clinincal features of sickle cell disease. Clinical Studies. I V. North-Holland, Amsterdam

    Google Scholar 

  227. Sinnott EW, Dunn LC, Dobzhansky T (1958) Principles of genetics, 5th edn. McGraw-Hill, New York

    Google Scholar 

  228. Slighton JL, Blechl AE, Smithies O (1980) Human fetal G-gamma-and A-gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged in these duplicated genes. Cell 21: 627–638

    Article  Google Scholar 

  229. Sly WS, Achard DT, Kaplan A (1977) Correction of enzyme deficient fibroblasts: evidence for a new type of pinocytosis receptor which mediates uptake of lysosomal enzymes ( Abstr ). Clin Res 25: 471A

    Google Scholar 

  230. Smithies O (1955) Grouped variations in the occurence of new protein components in normal human serum. Nature 175: 307–308

    Article  PubMed  CAS  Google Scholar 

  231. Smithies O (1955) Zone electrophoresis in starch gels: group variations in the serum proteins of normal human adults. Biochem J 61: 629–641

    PubMed  CAS  Google Scholar 

  232. Spielberg SP, Gordon GB, Blake DA, Goldstein DA, Her-long HF (1981) Predisposition to phenytoin hepatotoxicity assessed in vitro. N Engl J Med 305: 722–727

    Article  PubMed  CAS  Google Scholar 

  233. Spranger J (1972) The systemic mucopolysaccharidoses. Ergeb Inn Med Kinderheilkd 32: 165

    Article  PubMed  CAS  Google Scholar 

  234. Spritz RA, DeRiel JK, Forget BG, Weissman SM (1980) Complete nucleotide sequence of the human delta-globin gene. Cell 21: 639–646

    Article  PubMed  CAS  Google Scholar 

  235. Stamatoyannopoulos G (1972) The molecular basis of hemoglobin disease. Annu Rev Genet 6: 47

    Article  PubMed  CAS  Google Scholar 

  236. Stamatoyannopoulos G, Nienhuis AW (1994) Hemoglobin switching. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H (eds) The molecular basis of blood diseases, 2nd edn. Saunders, Philadelphia, pp 107–155

    Google Scholar 

  237. Strominger J (1989) Developmental biology of T-cell receptors. Science 244: 943–950

    Article  PubMed  CAS  Google Scholar 

  238. Swift M, Chase C (1979) Cancer in families with Xeroderma pigmentosum. J Natl Cancer Inst 62: 1415–1421

    PubMed  CAS  Google Scholar 

  239. Swift M, Reitnauer PJ, Morrell D et al (1987) Breast and other cancers in families with ataxia-teleangiectasia. N Engl J Med 316: 1289–1294

    Article  PubMed  CAS  Google Scholar 

  240. Taliaferro WH, Huck JG (1923) The inheritance of sickle cell anaemia in man. Genetics 8: 594

    PubMed  CAS  Google Scholar 

  241. Thein SL, Wainscoat JS, Lynch JR, Weatherall DJ, Sampietro M, Fiorelli G (1985) Direct detection of ß*39 thalassaemic mutation with Mae 1. Lancet 1: 1095

    Article  PubMed  CAS  Google Scholar 

  242. Thierfelder L, McRae C, Watkins H et al (1993) A familial hypertrophic cardiomyopathy locus maps to chromosome 15 q2. Proc Natl Acad Sci USA 90: 6270–6274

    Article  PubMed  CAS  Google Scholar 

  243. Thierfelder L, Watkins H, MacRee C et al (1994) a-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 77: 701–702

    Google Scholar 

  244. Tolleshaug H, Goldstein JL, Schneider WJ, Brown MS (1982) Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia. Cell 30: 715–724

    Article  PubMed  CAS  Google Scholar 

  245. Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302: 575–581

    Article  PubMed  CAS  Google Scholar 

  246. Tonegawa S (1986) Somatic generation of antibody diversity. Nature 302: 575–581

    Article  Google Scholar 

  247. Tynan K, Comeau K, Pearson M et al (1993) Mutation screening of complete fibrillin-i coding sequence: report of five new mutations, including two in 8-cysteine domains. Hum Mol Genet 2: 1813–1821

    Article  PubMed  CAS  Google Scholar 

  248. Udenfriend S, Cooper JR (1952) The enzymatic conversion of phenylalanine to tyrosine. J Biol Chem 194: 503

    PubMed  CAS  Google Scholar 

  249. a. Van Broeckhoven C (1995) Presenilins and Alzheimer’s disease. Nature Genet u: 230–232

    Google Scholar 

  250. Van Hoof F, Hers HG (1964) Ultrastructure of hepatic cells in Hurler’s disease (gargoylism). C R Acad Sci [D] 259: 1281

    Google Scholar 

  251. Van Poppet G, de Vogel N, Van Bladeren PJ, Kok FJ (1992) Increased cytogenetic damage in smokers deficient in glutathione S-transferase isozyme Mu. Carcinogenesis 13: 303–305

    Article  Google Scholar 

  252. Vogel F (1959) Moderne Probleme der Humangenetik. Ergeb Inn Med Kinderheilkd 12: 52–125

    Article  Google Scholar 

  253. Vogel F (1984) Relevant deviations in heterozygotes of autosomal-recessive diseases. Clin Genet 25: 381–415

    Article  PubMed  CAS  Google Scholar 

  254. Voigtlaender V (1977) Genetik der Neurodermitis. Z Hautkr 5 [Suppl]: 65–71

    Google Scholar 

  255. Vosberg H-P (1994) Myosin mutations in hypertrophic cardiomyopathy and functional implications. HERZ (in press)

    Google Scholar 

  256. Waller HD, Benöhr A C (1976) Enzymdefekte in Glykolyse und Nucleotidstoffwechsel roter Blutzellen bei nichtspherocytären hämolytischen Anämien. Klin Wochenschr 54: 803–850

    Article  PubMed  CAS  Google Scholar 

  257. Watkins H, MacRae C, Thierfelder L et al (1993) A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1 CO. Nat Genet 3: 333–337

    Article  PubMed  CAS  Google Scholar 

  258. Watson JD, Gilman M, Witkowski J, Zoller M (1992) Recombinant DNA, 2nd edn. Freeman, New York

    Google Scholar 

  259. Weatherall DJ (1994) The thalassemias. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H (eds) The molecular basis of blood diseases, 2nd edn. Saunders, Philadelphia, pp 157–205

    Google Scholar 

  260. Weatherall DJ, Clegg JB (1981) The thalassemia syndromes, 3rd edn. Blackwell, Oxford

    Google Scholar 

  261. Wedlund PJ, Aslanian WS, McAllister CB, Wilkinson GR, Branch RA (1984) Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin Pharmacol Ther 36: 773780

    Google Scholar 

  262. Weinshilboum RM (1983) Biochemical genetics of catecholamines in humans. Mayo Clin Proc 58: 319–330

    PubMed  CAS  Google Scholar 

  263. Weinshilboum RM, Sladek SL (1980) Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32: 651–662

    PubMed  CAS  Google Scholar 

  264. Wewers M, Casolaro A, Sellers SE et al (1987) Replacement therapy for alpha-i-antitrypsin deficiency associated with emphysema. N Engl J Med 316: 1055–1062

    Article  PubMed  CAS  Google Scholar 

  265. Wiwel NA (1993) Germ-line gene modification and disease prevention: some medical and ethical perspectives. Science 262: 553–538

    Article  Google Scholar 

  266. White JM (1976) The unstable haemoglobins. Br Med Bull 32: 219–222

    PubMed  CAS  Google Scholar 

  267. Wiencke JK, Kelsey KT, Lamela RA, Toscano WA Jr (1990) Human glutathione S-transferase deficiency as a marker of susceptibility to epoxide-induced cytogenetic damage. Cancer Res 50: 1585–1590

    PubMed  CAS  Google Scholar 

  268. Wilkie AOM, Buckle VJ, Harris PC et al (1990) Clinical features and molecular analysis of the athalassemia mental retardation syndromes. I. Cases due to deletions involving chromosome band 16 p13.366. Am J Hum Genet 46: 1112

    PubMed  CAS  Google Scholar 

  269. Wilkie AOM, Zietlin HC, Lindenbaum RH et al (1990) Clinical features and molecular analysis of the a thalassemia mental retardation syndromes. 2 cases without detectable abnormality of the a globin complex. Am J Hum Genet 46: 1127

    PubMed  CAS  Google Scholar 

  270. Williams AF, Barclay AN (1988) The immunoglobulin superfamily-domains for all surface recognition. Annu Rev Immunol 6: 381–405

    Article  PubMed  CAS  Google Scholar 

  271. Williamson R (1976) Direct measurement of the number of globin genes. Br Med Bull 32: 246–250

    PubMed  CAS  Google Scholar 

  272. Winkelstein JA, Colten HR (1989) Genetically determined disorders of the complement system. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2711–1738

    Google Scholar 

  273. Winters RW, Graham JB, Williams TF, McFalls VC, Burnett CH (1957) A genetic study of familial hypophosphatemia and viatmin D-resistant rickets. Trans Assoc Am Physicians 70: 234–242

    PubMed  CAS  Google Scholar 

  274. Wolf CR, Smith CAD, Bishop T, Forman D, Gough AC, Spur NK (1994) CYP2D6 genotyping and the association with lung cancer susceptibility. Pharmacogenetics 4: 104–106

    Article  PubMed  CAS  Google Scholar 

  275. Woo SLC, Lidsky AS, Guettler F et al (1983) Cloned human phenylalanine hydroxylase gene allows prenatal detection of classical phenylketonuria. Nature 306: 151–155

    Article  PubMed  CAS  Google Scholar 

  276. Woo SLC, Güttler F, Ledley FD, Lidsky AS, Kwok SCM, DiLella AG, Robson KJH (1985) The human poenylalanine hydroxylase gene. In: Berg K (ed) Medical genetics past, present, future. Liss, New York, pp 123–135

    Google Scholar 

  277. Yoshida A, Beutler E (1983) G-6-PD variants: another up-date. Ann Hum Genet 47: 25–38

    Article  PubMed  CAS  Google Scholar 

  278. Zhong S, Howie AF, Ketterer B, Taylor J, Hayes JD, Beckett GJ, Wathen G, Wolf CR, Spurr NK (1991) GlutathioneS-transferase Mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis 12: 1533–1537

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Humangenetik und Anthropologie, Im Neuenheimer Feld 328, 69120, Heidelberg, Germany

    Emeritus Professor Dr. Dr. h.c. Friedrich Vogel

  2. Division of Medical Genetics, School of Medicine, University of Washington, 98195, Seattle, WA, USA

    Arno G. Motulsky M.D. (Emeritus Professor of Medicine and Genetics)

Authors
  1. Emeritus Professor Dr. Dr. h.c. Friedrich Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arno G. Motulsky M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Vogel, F., Motulsky, A.G. (1997). Gene Action: Genetic Diseases. In: Human Genetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03356-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-03356-2_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-03358-6

  • Online ISBN: 978-3-662-03356-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation