Adult-onset genetic disease: Mechanisms, analysis and prediction

QJM: An International Journal of Medicine

Volumn 90, Issue 2, 1997, Pages 83-103

  Ravine, D ^a   Cooper, D N ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GENE ISOLATION; GENE LOCATION; GENE MUTATION; GENETIC DISORDER; HUMAN; MEDICAL GENETICS; PREDICTION; PRIORITY JOURNAL; RECOMBINANT DNA TECHNOLOGY; REVIEW;

EID: 0031025640     PISSN: 00335622     EISSN: None     Source Type: Journal    
DOI: 10.1093/qjmed/90.2.83     Document Type: Review

References (184)

1. Wilkie AOM. The molecular basis of genetic dominance. J Med Genet 1994; 31:89-98.
2. Monk M. Genomic imprinting. Genes Dev 1988; 2:921-5.
3. Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 1987; 99:371-82.
4. Reik W. Genome imprinting. Chap. 5 in Grosveld F, Kollias G, eds. Transgenic Animals. London, Academic Press, 1992:99-126.
5. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature 1993; 366:362-5.
6. Razin A, Cedar H. DNA methylation and genomic imprinting. Cell 1994; 77:473-6.
7. Efstratiadis A. Parental imprinting of autosomal mammalian genes. Curr Op Genet Dev 1994; 4:265-80.
8. Barlow DP. Imprinting: a gamete's point of view. Trends Genet 1994; 10:194-9.
9. Julier C, Hyer RN, Davies J, et al. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 1991; 354:155-9.
10. Heutink P, van der Mey AGL, Sandkuijl LA, et al. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum Molec Genet 1992; 1:7-10.
11. Mariman ECM, van Beersum SEC, Cremers CWRJ, Struycken PM, Ropers HH. Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity. Hum Genet 1995; 95:56-62.
12. Schinzel A, McKusick VA, Francomano C, Pearson PL. Report of the committee for clinical disorders and chromosome aberrations. In Cuticchia AJ, Pearson PL, eds. Human Gene Mapping 1993. A Compendium. Baltimore, Johns Hopkins University Press, 1993:735-72.
13. Harding AE. From the syndrome of Charcot, Marie and Tooth to disorders of peripheral myelin proteins. Brain 1995; 118:809-18.
14. Wolf U. The genetic contribution to the phenotype. Hum Genet 1995; 95:127-48.
15. Monari L, Chen SG, Brown P, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA 1994; 91:2839-42.
16. Giannelli F, Green PM, Sommer S, et al. Haemophilia B: database of point mutations and short additions and deletions - fifth edition. Nucleic Acids Res 1994; 22:3534-6.
17. Cooper DN, Clayton JF. DNA polymorphism and the study of disease associations. Hum Genet 1988; 78:299-312.
18. Humphries SE. DNA polymorphisms of the apolipoprotein genes - their use in the investigation of the genetic component of hyperlipidaemia and atherosclerosis. Atherosclerosis 1988; 72:89-108.
19. Sobell JL, Heston LL, Sommer SS Delineation of genetic predisposition to multifactorial disease: a general approach on the threshold of feasibility. Genomics 1992; 12:1-6.
20. Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994; 265:2037-47.
21. Cooper DN, Krawczak M. Human Gene Mutation. Oxford, BIOS Scientific Publishers, 1993.
22. Hall JG. Somatic mosaicism: observations related to clinical genetics. Am J Hum Genet 1988; 43:355-63.
23. Morton N. Sequential test for the detection of linkage. Am J Hum Genet 1955; 7:266-318.
24. Pakula AA, Sauer RT. Genetic analysis of protein stability and function. Ann Rev Genet 1989; 23:289-310.
25. Alber T. Mutational effects on protein stability. Ann Rev Biochem 1989; 58:765-98.
26. Wacey AI, Krawczak M, Kakkar VV, Cooper DN. Determinants of the factor IX mutational spectrum in haemophilia B: an analysis of missense mutations using a multi-domain molecular model of the activated protein. Hum Genet 1994; 94:594-608.
27. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975; 98:503-17.
28. Alwine JC, Kemp DJ, Stark GR. Method for detection of specific RNAs in gels by transfer to diazobenzyloxymethylpaper and hybridization with DNA probes. Proc Natl Acad Sci USA 1977; 74:5350-4.
29. Saiki RD, Scharf S, Faloona F, et al. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle-cell anemia. Science 1985; 230:1350-4.
30. Saiki RK, Gyllensten UB, Erlich HA. The polymerase chain reaction. Chap. 6 in Davies KE, ed. Genome Analysis: A Practical Approach. Oxford, IRL Press, 1988.
31. Williams JF. Optimization strategies for the polymerase chain reaction. Bio/Techniques 1989; 7:762-8.
32. Vosberg HP. The polymerase chain reaction: an improved method for the analysis of nucleic acids. Hum Genet 1989; 83:1-15.
33. Bloch W. A biochemical perspective of the polymerase chain reaction. Biochemistry 1991; 30:2735-47.
34. Cotton RGH. Detection of single base changes in nucleic acids. Biochem J 1989; 263:1-10.
35. Forrest S, Cotton RGH. Methods of detection of single base substitutions in clinical genetic practice. Mol Biol Med 1990; 7:451-9.
36. Rossiter BJF, Caskey CT. Molecular scanning methods of mutation detection. J Biol Chem 1990; 265:12753-6.
37. Cotton RGH, Rodrigues NR, Campbell RD. Reactivity of cytosine and thymine in single base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci USA 1988; 85:4397-401.
38. Montandon AJ, Green PM, Giannelli F, Bentley DR. Direct detection of point mutations by mismatch analysis: application to haemophilia B. Nucleic Acids Res 1989; 17:3347-57.
39. Myers RM, Sheffield VC, Cox DR. Detection of single-base changes in DNA: Ribonuclease cleavage and denaturing gradient gel electrophoresis. Chap.5 in Davies KE, ed. Genome Analysis: A Practical Approach, Oxford, IRL Press, 1988.
40. Fodde R, Losekoot M. Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutation 1994; 3:83-94.
41. Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 1989a; 5:874-9.
42. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polmorphisms. Proc Natl Acad Sci USA 1989b; 86:2766-70.
43. Hayashi K, Yandell DW. How sensitive is PCR-SSCP? Hum Mutation 1993; 2:338-46.
44. Gyllensten UB. PCR and DNA sequencing. Biotechniques 1989; 7:700-8.
45. Chehab FF. Molecular diagnostics: past, present and future. Hum Mutation 1993; 2:331-7.
46. Syvanen A-C, Landegren U. Detection of point mutations by solid-phase methods. Hum Mutation 1994; 3:172-9.
47. s-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 1983; 80:278-82.
48. Gershon D. DNA diagnostic tools for the 21st century. Nature Medicine 1995; 1:102-3.
49. Cooper DN, Krawczak M. The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Hum Genet 1990; 85:55-74.
50. Krawczak M, Reiss J, Cooper DN. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 1992; 90:41-54.
51. Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 1990; 247:49-56.
52. Lakich D, Kazazian HH, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nature Genet 1993; 5:236-41.
53. Naylor JA, Green PM, Rizza CR, Giannelli F. Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients. Hum Molec Genet 1993; 2:11-7.
54. Caskey CT, Pizzuti A, Fu Y-H, Fenwick RG, Nelson DL. Triplet repeat mutations in human disease. Science 1992; 256:784-9.
55. Rousseau F, Heitz D, Mandel J-L. The unstable and methylatable mutations causing the fragile X syndrome. Hum Mutation 1992; 1:91-6.
56. Rousseau F, Heitz D, Biancalana V, et al. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med 1991; 325:1673-81.
57. n. Science 1991; 252:1711-4.
58. Verkerk AJMH, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65:905-14.
59. Fu Y-H, Kuhl DPA, Pizzuti A, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of Sherman paradox. Cell 1991; 67:1047-58.
60. Richards RI, Holman K, Friend K, et al. Evidence of founder chromosomes in fragile X syndrome. Nature Genet 1992; 1:257-60.
61. Willems PJ. Dynamic mutations hit double figures. Nature Genet 1994; 8:213-5.
62. Harper PS, Newcombe PG. Age of onset and lifetable risks in genetic counselling for Huntington's disease. J Med Genet 1992; 29:239-42.
63. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72:971-83.
64. Duyao M, Ambrose C, Myers R, et al. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet 1993; 4:387-92.
65. Snell RG, MacMillan JC, Cheadle JP, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nature Genet 1993; 4:393-7.
66. n repeat length is the sex of the affected parent. Hum Molec Genet 1993; 2:1535-40.
67. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994; 330:1401-6.
68. n repeat in sporadic Huntington's disease. Nature Genet 1993; 5:168-72.
69. Read AP. Huntington's disease: testing the test. Nature Genet 1993; 4:329-30.
70. Craufurd D, Dodge A. Mutation size and age at onset in Huntington's disease. J Med Genet 1993; 30:1008-11.
71. Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, Ross CA. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Molec Genet 1993; 2:1547-9.
72. Kremer B, Squitieri F, Telenius H, et al. Molecular analysis of late onset Huntington's disease. J Med Genet 1993; 30:991-5.
73. MacDonald ME, Barnes G, Srinidhi J, et al. Gametic but not somatic instability of CAG repeat length in Huntington's disease. J Med Genet 1993; 30:982-6.
74. Goldberg YP, Kremer B, Andrew SE, et al. Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nature Genet 1993; 5:174-9.
75. Trottier Y, Biancalana V, Mandel JL. Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset. J Med Genet 1994; 31:377-82.
76. Telenius H, Kremer B, Goldberg YP, et al. Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nature Genet 1994; 6:409-414.
77. Andrew SE, Goldberg YP, Kremer B, et al. Huntington disease without CAG expansion: phenocopies or errors in assignment? Am J Hum Genet 1994; 54:852-63.
78. n changes in Huntington disease. Hum Molec Genet 1995; 4:189-95.
79. Almqvist E, Spence N, Nichol K, et al. Ancestral differences in the distribution of the δ2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes: insights into the genetic evolution of Huntington disease. Hum Molec Genet 1995; 4:207-14.
80. Green H. Human genetic diseases due to codon reiteration: relationship to an evolutionary mechanism. Cell 1993; 74:955-6.
81. Perutz MF, Johnson T, Suzuki M, Finch JT. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci USA 1994; 91:5355-8.
82. Skraastad MI, Verwest A, Bakker E, et al. Presymptomatic, prenatal and exclusion testing for Huntington disease using seven closely linked DNA markers. Am J Med Genet 1991; 39:217-22.
83. Lazarou LP, Meredith AL, Myring JM, et al. Huntington's disease: predictive testing and the molecular genetics laboratory. Clin Genet 1993; 43:150-6.
84. Ball DM, Harper PS. Presymptomatic testing for late-onset genetic disorders: lessons from Huntington' disease. FASEB J 1992; 6:2818-19.
85. Bachman DL, Wolf PA, Linn RT, et al. Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham study. Neurology 1993; 43:515-19.
86. Schellenberg GD. Genetic dissection of Alzheimer disease, a heterogeneous disorder. Proc Natl Acad Sci U.S.A. 1995; 92:8552-9.
87. Mullan M, Houlden H, Crawford F, Kennedy A, Rogues P, Rossor M. Age of onset in familial early onset Alzheimer's disease correlates with genetic aetiology. Am J Med Genet 1993; 48:129-30.
88. Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995; 375:754-60.
89. Cruts M, Backhovens H, Theuns J, et al. Genetic and physical characterization of the early-onset Alzheimer's disease AD3 locus on chromosome 14q24.3. Hum Molec Genet 1995; 4:1355-64.
90. Alzheimer's Disease Collaborative Group. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nature Genet 1995; 11:219-22.
91. Levy-Lahad E, Wijsman EM, Nemens E, et al. A familial Alzheimer's disease locus on chromosome 1. Science 1995a; 269:970-3.
92. Levy-Lahad E, Wasco W, Poorkaj P, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995b; 269:973-7.
93. Rogaev EI, Sherrington R, Rogaeva EA, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 1995; 376:775-8.
94. Felsenstein KM, Hunihan LW, Roberts SB. Altered cleavage and secretion of a recombinant beta-APP bearing the Swedish familial Alzheimer's disease mutation. Nature Genet 1994; 6:251-5.
95. Haass C, Hung AY, Selkoe DJ, Teplow DB. Mutations associated with a locus for familial Alzheimer's disease result in alternative processsing of amyloid beta-protein precursor. J Biol Chem 1994; 269:17741-8.
96. Goate A, Chartier-Harlin M-C, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991; 349:704-6.
97. Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 1991; 254:97-9.
98. Pericak-Vance MA, Bebout JL, Gaskell PJ, et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48:1034-50.
99. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261:921-3.
100. Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high activity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993; 90:1977-81.
101. Tsai MS, Tangalos EG, Petersen RC, et al. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet 1994; 54:643-9.
102. Chartier-Harlin MC, Parfitt M, Legrain S, et al. Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Molec Genet 1994; 3:569-74.
103. Polvikoski T, Sulkava R, Haltia M et al. Apolipoprotein E, dementia and cortical deposition of β-amyloid protein. N Engl J Med 1995; 333:1242-7.
104. St Clair D, Rennie M, Slorach E, Norrman J, Yates C et al. Apolipoprotein E ε4 allele is a risk factor for familial and sporadic presenile Alzheimer's disease in both homozygote and heterozygote carriers. J Med Genet 1995; 32:642-4.
105. Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Pericak-Vance MA, Joo SH. Association of apolipoprotein ε-4 allele with late onset familial and sporadic Alzheimer's disease. Neurology 1993; 43:1467-72.
106. Strittmatter WJ, Roses AD. Apolipoprotein E and Alzheimer disease. Proc Natl Acad Sci USA 1995; 92:4725-7.
107. Schmechel DE, Saunders AM, Strittmatter WJ, et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90:9649-53.
108. Kamboh MI, Sanghera DK, Ferrell RE, DeKosky ST. APOE*4-associated Alzheimer's disease risk is modified by α1-antichymotrypsin polymorphism. Nature Genet 1995; 10:486-8.
109. Okuizumi K, Onodera O, Namba Y, et al. Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease. Nature Genet 1995; 11:207-9.
110. Mullan M, Crawford F, Buchanan J. Technical feasibility of genetic testing for Alzheimer's disease. Alzheimer Disease & Associated Disorders 1994; 8:102-15.
111. Tuddenham EGD, Cooper DN. The Molecular Genetics of Haemostasis and its Inherited Disorders. Oxford University Press, Oxford 1994.
112. Tait RC, Walker ID, Perry DJ, et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87:106-12.
113. Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost 1988; 59:18-22.
114. Miletich J, Sherman L, Broze G Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 17:991-6.
115. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73:87-93.
116. Bertina RM, Koeleman BPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369:64-7.
117. Svensson PJ, Dahlbck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330:517-22.
118. Beauchamp NJ, Daly ME, Hamptom KK, Cooper PC, Preston FE, Peake IR. High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis. Br J Haematol 1994; 88:219-22.
119. Allaart CF, Poort SW, Rosendaal FR, Reitsma PH, Bertina RM, Brit E. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 1993; 341:134-8.
120. Henkens CMA, van der Meer J, Hillege JL, van der Schaaf W, Bom VJJ, Halie MR. The clinical expression of hereditary protein C and protein S deficiency: a relation to clinical thrombotic risk factors and to levels of protein C and protein S? Blood Coag Fibrinol 1993; 4:555-62.
121. Spek CA, Koster T, Rosendaal FR, Bertina RM, Reitsma PH. Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1995; 15:214-18.
122. Scopes D, Berg L-P, Krawczak M, Kakkar W, Cooper DN. Polymorphic variation in the human protein C (PROC) gene promoter can influence transcriptional efficiency in vitro. Blood Coag Fibrinol. 1995; 6:317-21.
123. Koeleman BPC, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84:1031-5.
124. Gandrille S, Greengard JS, Alhenc-Gelas M, et al. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. Blood 1995; 86:219-24.
125. Hallam PH, Millar DS, Krawczak M, Kakkar W, Cooper DN. Population differences in the frequency of the factor V Leiden variant among individuals with clinically symptomatic protein C deficiency. J Med Genet 1997; in press.
126. Zller B, Berntsdottir A, Garcia de Frutos P, Dahlbck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85:3518-23.
127. van Boven HH, Reitsma PH, Rosendaal FR, et al. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75:417-21.
128. Rosendaal FR, Heijboer H, Brit E, et al. Mortality in hereditary antithrombin-lll deficiency - 1830 to 1989. Lancet 1991; 337:260-2.
129. Allaart CF. Hereditary deficiency of protein S and protein C. PhD Thesis. University of Leiden, The Netherlands, 1994.
130. Lieske JC, Toback FG. Autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1993; 3:1442-50.
131. European Polycystic Kidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14kb transcript and lies within a duplicated region on chromosome 16. Cell 1994; 77:881-94.
132. Parfrey PS, Bear JC, Morgan J, et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med 1990; 323:1085-90.
133. Ravine D, Walker RG, Gibson RN, et al. Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet 1992; 340:1330-3.
134. Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics 1993;18:467-72.
135. Peters DJM, Spruit L, Saris JJ, et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nature Genet 1993; 5:359-62.
136. Mochizuki T, Wu G, Hayashi T, et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 1996; 272:1339-42.
137. de Almeida S , de Almeida E , Peters D, et al. Autosomal dominant polycystic kidney disease: evidence for the existence of a third locus in a Portuguese family. Hum Genet 1995; 96:83-8.
138. Daoust MC, Reynaud DM, Bichet DC, Somlo S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics 1995; 25:733-6.
139. Peters DJM, Sandkuijl LA, Snijdewint FGM, et al. Genetic heterogeneity of polycystic kidney disease in Europe. Contrib Nephrol 1992; 97:128-39.
140. Constantinou-Deltas CD, Papageorgiou E, Boteva K, et al. Genetic heterogeneity in adult dominant polycystic kidney disease in Cypriot families. Hum Genet 1995; 95:416-23.
141. Milutinovic J, Rust PF, Fialkow PJ, et al. Intrafamilial phenotypic expression of autosomal dominant polycystic kidney disease Am J Kid Dis 1992; 5:465-72.
142. Levine GN, Keaney JF, Vita JA. Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 1995; 332:512-21.
143. Hobbs HH, Brown MS, Goldstein JL, Russell DW. Deletion of exon encoding cysteine-rich repeat of low-density lipoprotein receptor alters its binding specificity in a subject with familial hypercholesterolemia. J Biol Chem 1986; 261:13114-20.
144. Soutar AK. Familial hypercholesterolaemia and LDL receptor mutations. J Intern Med 1992; 231:633-41.
145. Moorjani S, Roy M, Torres A, et al. Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia. Lancet 1993; 341:1303-6.
146. Kotze MJ, Davis HJ, Bissbort S, Langenhoven E, Brusnicky J, Oosthuizen CJ. Intrafamilial variability in the clinical expression of familial hypercholesterolemia: importance of risk factor determination for genetic counselling. Clin Genet 1993; 43:295-9.
147. Sass C, Giroux L-M, Ma Y, et al. Evidence for a cholesterol-lowering gene in a French-Canadian kindred with familial hypercholesterolemia. Hum Genet 1995; 96:21-6.
148. Tybjaerg-Hansen A, Humphries SE. Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease. Athersclerosis 1992; 96:91-107.
149. Myant NB. Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolaemia. Atherosclerosis 1994; 104:1-18.
150. Davignon J, Dufour R, Roy M, et al. Phenotypic heterogeneity associated with defective apolpoprotein B-1000 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred. Eur J Epidemiol 1992; 8(S1):10-17.
151. Pullinger CR, Hennessy LK, Chatterton JE, et al. Familial ligand-defective apolipoprotein B. J Clin Invest 1995; 95:1225-34.
152. Soussi T. The p53 tumor suppressor gene: from molecular biology to clinical investigation. Chap. 7 in Cowell JK, ed. Molecular Genetics of Cancer. Oxford, BIOS Scientific Publishers 1995:135-78.
153. Burt RW. Genetics of colon cancer: impact of inheritance on colon cancer risk. Annu Rev Med 1995; 46:371-9.
154. Nagase H, Nakamura Y. Mutations of the APC (Adenomatous Polyposis Coli) gene. Hum Mutation 1993; 2:425-34.
155. Dunlop MG. Molecular genetics of colon cancer. Chap. 6 in Cowell JK, ed. Molecular Genetics of Cancer. Oxford, BIOS Scientific Publishers, 1995:113-34.
156. Bishop DT. Genetics of breast and ovarian cancer. Chap. 5 in Molecular Genetics of Cancer. Cowell JK, ed. Molecular Genetics of Cancer. Oxford, BIOS Scientific Publishers, 1995:93-111.
157. Shattuck-Eidens D, McClure M, Simard J et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. JAMA 1995; 273:535-41.
158. Gayther SA, Warren W, Mazoyer S, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nature Genet 1995; 1:428-33.
159. Durocher F, Shattuck-Eidens D, McClure M, et al. Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Molec Genet 1996; 5:835-42.
160. Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 1994; 265:2088-90.
161. Wooster R, Bignell G, Lancaster J et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378:789-92.
162. Tavtigian SV, Simard J, Rommens J, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet 1996; 12:333-7.
163. Phelan CM, Rebbeck TR, Weber BL, et al. Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus. Nature Genet 1996; 12:309-11.
164. Propping P, Nöthen MM. Schizophrenia: genetic tools for unraveling the nature of a complex disorder. Proc Natl Acad Sci USA 1995; 92:7607-8.
165. McGuffin P, Owen MJ, Farmer AE. Genetic basis of schizophrenia. Lancet 1995; 346:678-82.
166. Plomin R, Owen MJ, McGuffin P. The genetic basis of complex human behaviors. Science 1994; 264:1733-9.
167. Owen M, McGuffin P. The molecular genetics of schizophrenia; blind alleys, acts of faith, and difficult science. Br Med J 1992; 305:664-5.
168. Wang S, Sun C, Walczak CA, et al. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22. Nature Genet 1995; 10:41-6.
169. Straub RE, MacLean CJ, O'Neill FA, et al. A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nature Genet 1995; 11:287-93.
170. Moises HW, Yang L, Krisbjarnarson H, et al. An international two-stage genome-wide search for schizophrenia susceptibility genes. Nature Genet 1995; 11:321-4.
171. Schwab SG, Albus M, Hallmayer J, et al. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis. Nature Genet 1995; 11:325-7.
172. Pulver AE, Lasseter VK, Kasch L et al. Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. Am J Med Genet 1995; 60:252-60.
173. Lindsay EA, Morris MA, Gos A, et al. Schizophrenia and chromosomal deletions within 22q11.2. Am J Hum Genet 1995; 56:1502-3.
174. Karayiorgou M, Morris MA, Morrow B, et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci USA 1995; 92:7612-16.
175. Vallada HP, Gill M, Sham P. Linkage studies on chromosome 22 in familial schizophrenia. Am J Med Genet 1995; 60:139-46.
176. Morris AG, Gaitonde E, McKenna PJ, Mollon JD, Hunt DM. CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset. Hum Molec Genet 1995; 4:1957-61
177. Gelernter J. Genetics of bipolar affective disorder: time for another reinvention? Am J Hum Genet 1995; 56:1262-6.
178. Lim LCC, Powell J, Sham P, et al. Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder. Am J Med Genet 1995; 60:325-31.
179. Blackwood DHR, Lin He, Morris SW, et al. A locus for bipolar affective disorder on chromosome 4p. Nature Genet 1996; 12:427-30.
180. Berrettini WH, Ferraro TN, Goldin LR, et al. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci USA 1994; 91:5918-21.
181. Freimer NB, Reus VI, Escamilla MA, et al. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23. Nature Genet 1996; 12:436-41.
182. Straub RE, Lehner T, Luo Y, et al. A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3. Nature Genet 1994; 8:291-6.
183. McMahon FJ, Stine OC, Meyers DA, Simpson SG, DePaulo JR. Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet 1995; 56:1277-86.
184. Mclnnis MG, McMahon FJ, Chase GA, Simpson SG, Ross CA, DePaulo JR. Anticipation in bipolar affective disorder. Am J Hum Genet 1993; 53:385-90.