Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 526, Issue 1-2, 2003, Pages 93-125

  Mohrenweiser, Harvey W ^a   Wilson III, David M ^b   Jones, Irene M ^a  

^a LAWRENCE LIVERMORE NATIONAL LABORATORY   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Challenges and complexities; Disease risk; Human DNA repair genes

Indexed keywords

ATM PROTEIN; DNA; DNA GLYCOSYLTRANSFERASE; DNA POLYMERASE; DOUBLE STRANDED DNA; ENDONUCLEASE; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; PROTEIN MLH1; PROTEIN MSH2; PROTEIN MSH3; PROTEIN MSH6;

ALKYLATION; AMINO ACID SUBSTITUTION; ARTICLE; BASE MISPAIRING; CANCER RISK; CANCER SUSCEPTIBILITY; CELL CYCLE; CELL RESPIRATION; DISEASE PREDISPOSITION; DNA ADDUCT; DNA DAMAGE; DNA PROTEIN COMPLEX; DNA REPAIR; DNA REPLICATION; DNA STRAND BREAKAGE; EXCISION REPAIR; GENE DELETION; GENE FUNCTION; GENE INSERTION; GENETIC ANALYSIS; GENETIC CODE; GENETIC EPIDEMIOLOGY; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HEALTH HAZARD; HUMAN; MISMATCH REPAIR; MOLECULAR RECOGNITION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION;

EID: 0242501504     PISSN: 00275107     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0027-5107(03)00049-6     Document Type: Article

References (151)

1. Sachidanandam R., Weissman D., Schmidt S.C., Kakol J.M., Stein L.D., Marth G., Sherry S., Mullikin J.C., Mortimore B.J., Willey D.L.et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 409:2001;928-933.
2. Collins F.S., Brooks L.D., Chakravarti A. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 8:1998;1229-1231.
3. Cambien F., Poirier O., Nicaud V., Herrmann S.M., Mallet C., Ricard S., Behague I., Hallet V., Blanc H., Loukaci V.et al. Sequence diversity in 36 candidate genes for cardiovascular disorders. Am. J. Hum. Genet. 65:1999;183-191.
4. Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N.et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. 22:1999;231-238.
5. Halushka M.K., Fan J.B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat. Genet. 22:1999;239-247.
6. Ohnishi Y., Tanaka T., Yamada R., Suematsu K., Minami M., Fujii K., Hoki N., Kodama K., Nagata S., Hayashi T.et al. Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population. Hum. Genet. 106:2000;288-292.
7. Yamada R., Tanaka T., Ohnishi Y., Suematsu K., Minami M., Seki T., Yukioka M., Maeda A., Murata N., Saiki O.et al. Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population. Hum. Genet. 106:2000;293-297.
8. Begg C.B. On the use of familial aggregation in population-based case probands for calculating penetrance. J. Natl. Cancer Inst. 94:2002;1221-1226.
9. Hopper J.L. Genetic epidemiology of female breast cancer. Semin. Cancer Biol. 11:2001;367-374.
10. Peterson G.M. Familial aggregation: Sorting susceptibility from shared environment. J. Natl. Cancer Inst. 92:2000;1114-1115.
11. Pharoah P.D., Antoniou A., Bobrow M., Zimmern R.L., Easton D.F., Ponder B.A. Polygenic susceptibility to breast cancer and implications for prevention. Nat. Genet. 31:2002;33-36.
12. Hoeijmakers J.H. Genome maintenance mechanisms for preventing cancer. Nature. 411:2001;366-374.
13. Lindahl T., Wood R.D. Quality control by DNA repair. Science. 286:1999;1897-1905.
14. Norbury C.J., Hickson I.D. Cellular responses to DNA damage. Annu. Rev. Pharmacol. Toxico. 41:2001;367-401.
15. Ronen A., Glickman B.W. Human DNA repair genes. Environ. Mol. Mutagen. 37:2001;241-283.
16. Bernstein C., Bernstein H., Payne C.M., Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res. 511:2002;145-178.
17. Wood R.D., Mitchell M., Sgouros J., Lindahl T. Human DNA repair genes. Science. 291:2001;1284-1289.
18. Margison G.P., Santibanez-Koref M.F. O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. Bioessays. 24:2002;255-266.
19. Gerson S.L. Clinical relevance of MGMT in the treatment of cancer. J. Clin. Oncol. 20:2002;2388-2399.
20. Bellacosa A. Functional interactions and signaling properties of mammalian DNA mismatch repair proteins. Cell Death Differ. 8:2001;1076-1092.
21. Hsieh P. Molecular mechanisms of DNA mismatch repair. Mutat. Res. 486:2001;71-87.
22. Marti T.M., Kunz C., Fleck O. DNA mismatch repair and mutation avoidance pathways. J. Cell Physiol. 191:2002;28-41.
23. Modrich P. Strand-specific mismatch repair in mammalian cells. J. Biol. Chem. 272:1997;24727-24730.
24. Genschel J., Bazemore L.R., Modrich P. Human exonuclease I is required for 5′ and 3′ mismatch repair. J. Biol. Chem. 277:2002;13302-13311.
25. Muller A., Fishel R. Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Invest. 20:2002;102-109.
26. Irving J.A., Hall A.G. Mismatch repair defects as a cause of resistance to cytotoxic drugs. Expert Rev. Anticancer Ther. 1:2001;149-158.
27. Lindahl T. Instability and decay of the primary structure of DNA. Nature. 362:1993;709-715.
28. Scharer O.D., Jiricny J. Recent progress in the biology. Bioessays. 23:2001;270-281.
29. Wilson D.M. III, Barsky D. The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA. Mutat. Res. 485:2001;283-307.
30. Thompson L.H., West M.G. XRCC1 keeps DNA from getting stranded. Mutat. Res. 459:2000;1-18.
31. Tomkinson A.E., Mackey Z.B. Structure and function of mammalian DNA ligases. Mutat. Res. 407:1998;1-9.
32. Wilson S.H. Mammalian base excision repair and DNA polymerase beta. Mutat. Res. 407:1998;203-215.
33. Matsumoto Y. Molecular mechanism of PCNA-dependent base excision repair. Prog. Nucleic Acid Res. Mol. Biol. 68:2001;129-138.
34. Lindahl T. Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat. Res. 462:2000;129-135.
35. Barnes D.E., Tomkinson A.E., Lehmann A.R., Webster A.D., Lindahl T. Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. Cell. 69:1992;495-503.
36. Levin D.S., McKenna A.E., Motycka T.A., Matsumoto Y., Tomkinson A.E. Interaction between PCNA and DNA ligase I is critical for joining of Okazaki fragments and long-patch base-excision repair. Curr. Biol. 10:2000;919-922.
37. Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L., Williams G.T., Hodges A.K., Davies D.R., David S.S., Sampson J.R.et al. Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat. Genet. 30:2002;227-232.
38. Friedberg E.C. How nucleotide excision repair protects against cancer. Nat. Rev. Cancer. 1:2001;22-33.
39. Batty D.P., Wood R.D. Damage recognition in nucleotide excision repair of DNA. Gene. 241:2000;193-204.
40. de Boer J., Hoeijmakers J.H. Nucleotide excision repair and human syndromes. Carcinogenesis. 21:2000;453-460.
41. Petit C., Sancar A., coli to man E. Biochimie. 81:1999;15-25.
42. Tornaletti S., Hanawalt P.C. Effect of DNA lesions on transcription elongation. Biochimie. 81:1999;139-146.
43. Svejstrup J.Q. Mechanisms of transcription-coupled DNA repair. Nat. Rev. Mol. Cell Biol. 3:2002;21-29.
44. Balajee A.S., Bohr V.A. Genomic heterogeneity of nucleotide excision repair. Gene. 250:2000;15-30.
45. Cleaver J.E., Crowley E. UV damage. Front. Biosci. 7:2002;d1024-d1043.
46. Moriwaki S., Kraemer K.H. Xeroderma pigmentosum - bridging a gap between clinic and laboratory. Photodermatol. Photoimmunol. Photomed. 17:2001;47-54.
47. Cromie G.A., Connelly J.C., Leach D.R. Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans. Mol. Cell. 8:2001;1163-1174.
48. Haber J.E. Partners and pathways repairing a double-strand break. Trends Genet. 16:2000;259-264.
49. Pierce A.J., Stark J.M., Araujo F.D., Moynahan M.E., Berwick M., Jasin M. Double-strand breaks and tumorigenesis. Trends Cell Biol. 11:2001;S52-S59.
50. van den Bosch M., Lohman P.H., Pastink A. DNA double-strand break repair by homologous recombination. Biol. Chem. 383:2002;873-892.
51. Baumann P., West S.C. Role of the human RAD51 protein in homologous recombination and double-stranded-break repair. Trends Biochem. Sci. 23:1998;247-251.
52. Sonoda E., Takata M., Yamashita Y.M., Morrison C., Takeda S. Homologous DNA recombination in vertebrate cells. Proc. Natl. Acad. Sci. USA. 98:2001;8388-8394.
53. Thompson L.H., Schild D. Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat. Res. 477:2001;131-153.
54. Van Dyck E., Stasiak A.Z., Stasiak A., West S.C. Binding of double-strand breaks in DNA by human Rad52 protein. Nature. 398:1999;728-731.
55. Connelly J.C., Leach D.R. Tethering on the brink: the evolutionarily conserved Mre11-Rad50 complex. Trends Biochem. Sci. 27:2002;410-418.
56. Hopfner K.P., Putnam C.D., Tainer J.A. DNA double-strand break repair from head to tail. Curr. Opin. Struct. Biol. 12:2002;115-122.
57. Paull T.T. New glimpses of an old machine. Cell. 107:2001;563-565.
58. Lee B.I., Wilson D.M. III The RAD2 domain of human exonuclease 1 exhibits 5′ to 3′ exonuclease and flap structure-specific endonuclease activities. J. Biol. Chem. 274:1999;37763-37769.
59. Chen X.B., Melchionna R., Denis C.M., Gaillard P.H., Blasina A., Van de Weyer I., Boddy M.N., Russell P., Vialard J., McGowan C.H. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol. Cell. 8:2001;1117-1127.
60. Venkitaraman A.R. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 108:2002;171-182.
61. Thompson L.H., Schild D. Recombinational DNA repair and human disease. Mutat. Res. 509:2002;49-78.
62. Doherty A.J., Jackson S.P. DNA repair: how Ku makes ends meet. Curr. Biol. 11:2001;R920-924.
63. Lieber M.R. The biochemistry and biological significance of nonhomologous DNA end joining: an essential repair process in multicellular eukaryotes. Genes Cells. 4:1999;77-85.
64. Huang J., Dynan W.S. Reconstitution of the mammalian DNA double-strand break end-joining reaction reveals a requirement for an Mre11/Rad50/NBS1-containing fraction. Nucleic Acids Res. 30:2002;667-674.
65. Riballo E., Doherty A.J., Dai Y., Stiff T., Oettinger M.A., Jeggo P.A., Kysela B. Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. J. Biol. Chem. 276:2001;31124-31132.
66. Carr A.M. DNA structure dependent checkpoints as regulators of DNA repair. DNA Repair. 1:2002;983-994.
67. Jackson S.P. Sensing and repairing DNA double-strand breaks. Carcinogenesis. 23:2002;687-696.
68. Nyberg K.A., Michelson R.J., Putnam C.W., Weinert T.A. Toward maintaining the genome: DNA damage and replication checkpoints. Annu. Rev. Genet. 36:2002;617-656.
69. D'Amours D., Jackson S.P. The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat. Rev. Mol. Cell Biol. 3:2002;317-327.
70. Lehmann A.R. Replication of damaged DNA in mammalian cells: new solutions to an old problem. Mutat. Res. 509:2002;23-34.
71. Petrini J.H. The Mre11 complex and ATM: collaborating to navigate S phase. Curr. Opin. Cell Biol. 12:2000;293-296.
72. Burgers P.M., Koonin E.V., Bruford E., Blanco L., Burtis K.C., Christman M.F., Copeland W.C., Friedberg E.C., Hanaoka F., Hinkle D.C.et al. Eukaryotic DNA polymerases: proposal for a revised nomenclature. J. Biol. Chem. 276:2001;43487-43490.
73. Friedberg E.C., Wagner R., Radman M. Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science. 296:2002;1627-1630.
74. Goodman M.F. Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu. Rev. Biochem. 71:2002;17-50.
75. Prakash S., Prakash L. Translesion DNA synthesis in eukaryotes: a one- or two-polymerase affair. Genes Dev. 16:2002;1872-1883.
76. Mohrenweiser H.W., Xi T., Vazquez-Matias J., Jones I.M. Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans. Cancer Epidemiol. Biomarkers Prev. 11:2002;1054-1064.
77. Bell D.W., Wahrer D.C., Kang D.H., MacMahon M.S., FitzGerald M.G., Ishioka C., Isselbacher K.J., Krainer M., Haber D.A. Common nonsense mutations in RAD52. Cancer Res. 59:1999;3883-3888.
78. Ma X., Jin Q., Forsti A., Hemminki K., Kumar R. Single nucleotide polymorphism analyses of the human proliferating cell nuclear antigen (pCNA) and flap endonuclease (FEN1) genes. Int. J. Cancer. 88:2000;938-942.
79. Thorstenson Y.R., Shen P., Tusher V.G., Wayne T.L., Davis R.W., Chu G., Oefner P.J. Global analysis of ATM polymorphism reveals significant functional constraint. Am. J. Hum. Genet. 69:2001;396-412.
80. Nickerson D.A., Taylor S.T., Weiss K.M., Clark A.G., Hutchinson R.G., Stengard J., Salomaa V., Vartianinen E., Boerwinkle E., Sing C.F. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat. Genet. 19:1998;233-240.
81. Rieder M.J., Taylor S.L., Clark A.G., Nickerson D.A. Sequence variation in the human angiotensin converting enzyme. Nat. Genet. 22:1999;59-62.
82. Wu X., Gu J., Amos C.I., Jiang H., Hong W.K., Spitz M.R. A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and control. Cancer. 83:1998;1118-1127.
83. Wu X., Gu J., Hong W.K., Lee J.J., Amos C.I., Jiang H., Winn R.J., Fu K.K., Cooper J., Spitz M.R. Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract. J. Natl. Cancer Inst. 90:1998;1393-1399.
84. Cloos J., Nieuwenhuis E.J.C., Boomsma D.I., Kuik D.J., van der Sterre M.L.T., Arwert F., Snow G.B., Braakhuis B.J.M. Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes. J. Natl. Cancer Inst. 91:1999;1125-1130.
85. Roberts S.A., Spreadborough A.R., Bulman B., Barber J.B.P., Evans D.G.R., Scott D. Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer. Am. J. Hum. Genet. 65:1999;784-794.
86. Wu X., Spitz M.R., DeAndrade M., Benowitz N.L., Swan G.E. Genetic influence on mutagen sensitivity: a twin study. Proc. Am. Assoc. Cancer Res. 41:2000;437.
87. L. Grossman, G. Matanoski, E. Farmer, et. al., DNA repair as a susceptibility factor in chronic diseases in human populations, in: M. Dizdaroglu, A.E. Karakaya, (Eds.), Advances in DNA Damage and Repair, Kluwer Academic Publishers, New York, 1999, pp. 149-167.
88. M. Berwick, G. Matullo, P. Vineis, Studies of DNA repair and human cancer: an update, in: S.H. Wilson, W.A. Suk, (Eds.), Biomarkers of Environmentally Associated Disease: Technologies, Concepts and Perspectives, Lewis Publishers, Boca Raton, 2002, pp. 84-105.
89. Berwick M., Vineis P. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J. Natl. Cancer Inst. 92:2000;874-897.
90. Wu X., Gu J., Patt Y., Hassan M., Spitz M.R., Beasley R.P., Hwang L.Y. Mutagen sensitivity as a susceptibility marker for human hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev. 7:1998;567-570.
91. Ihle J.N. The challenges of translating knockout phenotypes into gene function. Cell. 102:2000;131-134.
92. Ishikawa T., Ide F., Qin X., Zhang S., Takahashi Y., Sekiguchi M., Tanaka K., Nakatsuru Y. Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies. Mutat. Res. 477:2001;41-49.
93. Kaina B., Fritz G., Ochs K., Haas S., Grombacher T., Dosch J., Christmann M., Lund P., Gregel C.M., Becker K. Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions. Mutat. Res. 405:1998;179-191.
94. Meira L.B., Devaraj S., Kisby G.E., Burns D.K., Daniel R.L., Hammer R.E., Grundy S., Jialal I., Friedberg E.C. Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Res. 61:2001;5552-5557.
95. Meira L.B., Reis A.M., Cheo D.L., Nahari D., Burns D.K., Friedberg E.C. Cancer predisposition in mutant mice defective in multiple genetic pathways: uncovering important genetic interactions. Mutat. Res. 477:2001;51-58.
96. Goss K.H., Risinger M.A., Kordich J.J., Sanz M.M., Straughen J.E., Slovek L.E., Capobianco A.J., German J., Boivin G.P., Groden J. Enhanced tumor formation in mice heterozygous for Blm mutation. Science. 297:2002;2051-2053.
97. Kucherlapati M., Yang K., Kuraguchi M., Zhao J., Lia M., Heyer J., Kane M.F., Fan K., Russell R., Brown A.M.et al. Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression. Proc. Natl. Acad. Sci. USA. 99:2002;9924-9929.
98. Spring K., Ahangari F., Scott S.P., Waring P., Purdie D.M., Chen P.C., Hourigan K., Ramsay J., McKinnon P.J., Swift M.et al. Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. Nat. Genet. 32:2002;185-190.
99. Yu Y., Okayasu R., Weil M.M., Silver A., McCarthy M., Zabriskie R., Long S., Cox R., Ullrich R.L. Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene. Cancer Res. 61:2001;1820-1824.
100. Worgul B.V., Smilenov L., Brenner D.J., Junk A., Zhou W., Hall E.J. Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. Proc. Natl. Acad. Sci. USA. 99:2002;9836-9839.
101. Cheo D.L., Meira L.B., Burns D.K., Reis A.M., Issac T., Friedberg E.C. Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors. Cancer Res. 60:2000;1580-1584.
102. Manenti G., Nomoto T., De Gregorio L., Gariboldi M., Stefania Falvella F., Nagao M., Dragani T.A. Predisposition to lung tumorigenesis. Toxicol. Lett. 112/113:2000;257-263.
103. Tripodis N., Hart A.A., Fijneman R.J., Demant P. Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five interactions in half of the mouse genome. J. Natl. Cancer Inst. 93:2001;1484-1491.
104. Bilger A., Shoemaker A.R., Gould K.A., Dove W.F. Manipulation of the mouse germline in the study of Min-induced neoplasia. Semin. Cancer Biol. 7:1996;249-260.
105. Shoemaker A.R., Moser A.R., Midgley C.A., Clipson L., Newton M.A., Dove W.F. A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice. Proc. Natl. Acad. Sci. USA. 95:1998;10826-10831.
106. Silverman K.A., Koratkar R., Siracusa L.D., Buchberg A.M. Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia. Genome Res. 12:2002;88-97.
107. Goode E.L., Ulrich C.M., Potter J.D. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol. Biomarkers Prev. 11:2002;1513-1530.
108. Hu J.J., Smith T.R., Miller M.S., Lohman K., Case L.D. Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ. Mol. Mutagen. 39:2002;208-215.
109. Hu J.J., Smith T.R., Miller M.S., Mohrenweiser H.W., Golden A., Case L.D. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 22:2001;917-922.
110. Ferrer-Costa C., Orozco M., de la Cruz X. Characterization of disease-associated single amino acid polymorphisms in terms of sequence and structure properties. J. Mol. Biol. 315:2002;771-786.
111. Ng P.C., Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 11:2001;863-874.
112. Ng P.C., Henikoff S. Accounting for human polymorphisms predicted to affect protein function. Genome Res. 12:2002;436-446.
113. Sunyaev S.R., Lathe W.C., Ramensky V.E., Bork I. SNP frequencies in human genes, an excess of rare alleles and differing modes of selection. Trends Genet. 16:2000;335-337.
114. Wang Z., Moult J. SNPs, protein structure, and disease. Hum. Mutat. 17:2001;263-270.
115. Chasman D., Adams R.M. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J. Mol. Biol. 307:2001;683-706.
116. Sunyaev S., Ramensky V., Koch I., Lathe W. III, Kondrashov A.S., Bork P. Prediction of deleterious human alleles. Hum. Mol. Genet. 10:2001;591-597.
117. Savas S., Knight J.A., Briollais L., Ozcelik H. Prediction of deleterious single nucleotide polymorhisms (SNPs) in DNA repair genes for breast cancer association studies. Cancer Epidemiol. Biomarkers Prev. 11:2002;1178s.
118. Ramensky V., Bork P., Sunyaev S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 30:2002;3894-3900.
119. Hadi M.Z., Coleman M.A., Fidelis K., Mohrenweiser H.W., Wilson D.M. III Functional characterization of Ape1 variants identified in the human population. Nucleic Acids Res. 28:2000;3871-3879.
120. Audebert M., Radicella J.P., Dizdaroglu M. Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein. Nucleic Acids Res. 28:2000;2672-2678.
121. Dherin C., Radicella J.P., Dizdaroglu M., Boiteux S. Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations. Nucleic Acids Res. 27:1999;4001-4007.
122. de Boer J.G. Polymorphisms in DNA repair and environmental interactions. Mutat. Res. 509:2002;201-210.
123. Klungland A., Lindahl T. Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1). EMBO J. 16:1997;3341-3348.
124. Kubota Y., Nash R.A., Klungland A., Schar P., Barnes D.E., Lindahl T. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J. 15:1996;6662-6670.
125. Matsumoto Y., Kim K., Hurwitz J., Gary R., Levin D.S., Tomkinson A.E., Park M.S. Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins. J. Biol. Chem. 274:1999;33703-33708.
126. Nicholl I.D., Nealon K., Kenny M.K. Reconstitution of human base excision repair with purified proteins. Biochemistry. 36:1997;7557-7566.
127. Pascucci B., Maga G., Hubscher U., Bjoras M., Seeberg E., Hickson I.D., Villani G., Giordano C., Cellai L., Dogliotti E. Reconstitution of the base excision repair pathway for 7,8-dihydro-8- oxoguanine with purified human proteins. Nucleic Acids Res. 30:2002;2124-2130.
128. Pascucci B., Stucki M., Jonsson Z.O., Dogliotti E., Hubscher U. Long patch base excision repair with purified human proteins. DNA ligase I as patch size mediator for DNA polymerases delta and epsilon. J. Biol. Chem. 274:1999;33696-33702.
129. Srivastava D.K., Berg B.J., Prasad R., Molina J.T., Beard W.A., Tomkinson A.E., Wilson S.H. Mammalian abasic site base excision repair. Identification of the reaction sequence and rate-determining steps. J. Biol. Chem. 273:1998;21203-21209.
130. Aboussekhra A., Biggerstaff M., Shivji M.K., Vilpo J.A., Moncollin V., Podust V.N., Protic M., Hubscher U., Egly J.M., Wood R.D. Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell. 80:1995;859-868.
131. Araki M., Masutani C., Maekawa T., Watanabe Y., Yamada A., Kusumoto R., Sakai D., Sugasawa K., Ohkuma Y., Hanaoka F. Reconstitution of damage DNA excision reaction from SV40 minichromosomes with purified nucleotide excision repair proteins. Mutat. Res. 459:2000;147-160.
132. Mu D., Park C.H., Matsunaga T., Hsu D.S., Reardon J.T., Sancar A. Reconstitution of human DNA repair excision nuclease in a highly defined system. J. Biol. Chem. 270:1995;2415-2418.
133. Ostling O., Johanson K.J. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun. 123:1984;291-298.
134. Singh N.P., McCoy M.T., Tice R.R., Schneider E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell. Res. 175:1988;184-191.
135. L. Breiman, Forests - Random Features, University of California, Berkeley, CA, 1999.
136. L. Breiman http://oz.berkeley.edu/users/breiman /, 2002.
137. J.M. Fridlyand, Resampling Methods for Variable Selection and Classification: Applications to Genomics, Statistics Department, University of California, Berkeley, CA, 2001.
138. http://bear.fhcrc.org/∼ingor/logic /.
139. Kooperberg C., Ruczinski I., LeBlanc M.L., Hsu L. Sequence analysis using logic regression. Genet. Epidemol. 21(Supple. 1):2001;S626-S631.
140. Jackson-Grusby L. Modeling cancer in mice. Oncogene. 21:2002;5504-5514.
141. Meuwissen R., Jonkers J., Berns A. Mouse models for sporadic cancer. Exp. Cell Res. 264:2001;100-110.
142. Tuveson D.A., Jacks T. Technologically advanced cancer modeling in mice. Curr. Opin. Genet. Dev. 12:2002;105-110.
143. Van Dyke T., Jacks T. Cancer modeling in the modern era: progress and challenges. Cell. 108:2002;135-144.
144. Comings D.E., Gade-Andavolu R., Gonzalez N., Wu S., Muhleman D., Blake H., Dietz G., Saucier G., MacMurray J.P. Comparison of the role of dopamine, serotonin, and noradrenaline genes in ADHD, ODD and conduct disorder: multivariate regression analysis of 20 genes. Clin. Genet. 57:2000;178-196.
145. Comings D.E., Gade-Andavolu R., Gonzalez N., Wu S., Muhleman D., Blake H., Mann M.B., Dietz G., Saucier G., MacMurray J.P. A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory. Clin. Genet. 58:2000;375-385.
146. Pastinen T., Perola P., Niini P., Terwilliger N.P., Salomaa V., Vartiainen E., Peltonen L., Syvanen A. Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum. Mol. Genet. 7:1998;1454-1462.
147. Noble E.P., Zhang G., Ritchie T., Lawford R.R., Grosser S.C., Young R.M., Sparkes R.S. D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism. Psychiatry Res. 16:1998;133-147.
148. Nelson M.R., Kardia S.L., Ferrell R.E., Sing C.F. A combinatorial partitioning method to identify multilocus genotypic partitions that predict quantitative trait variation. Genome Res. 11:2001;458-470.
149. Ritchie M.D., Hahn L.W., Roodi N., Bailey L.R., Dupont W.D., Parl F.F., Moore J.H. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am. J. Hum. Gene. 69:2001;138-147.
150. Breiman L. Statistical modeling: the two cultures. Stat. Sci. 16:2000;199-231.
151. Kaiser J. Population databases boom, from Iceland to the US. Science. 298:2002;1158-1161.