“They all talked at once, their voices insistent and contradictory and impatient, making of unreality a possibility, then a probability, then an incontrovertible fact, as people will when their desires become words.” —W. Faulkner, The Sound and the Fury, 1929
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Brookes, A. The essence of SNPs. Gene 234, 177–186 (1999).
Collins, F.S. The human genome project and the future of medicine. Ann. N. Y. Acad. Sci. 882, 42–55 (1999).
Collins, F.S. Genetics: an explosion of knowledge is transforming clinical practice. Geriatrics 54, 41–47 (1999).
Russo, E. Bypassing peer review. The Scientist 14, 1–12 (2000).
Sander, C. Genomic medicine and the future of health care. Science 287, 1977–1978 (2000).
Cargill, M. et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature Genet. 22, 231–238 (1999).
Chakravarti, A. Population genetics—making sense out of sequence. Nature Genet. 21, 56–60 (1999).
Collins, F., Brooks, L. & Chakravarti, A. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 8, 1229–1231 (1998).
Pastinen, T. et al. Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population.l. Hum. Mol. Genet. 7, 1453–1462 (1998).
Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet. 22, 139–144 (1999).
Wang, D. & Lander, E. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 (1998).
Zöllner, S. & von Haeseler, A. A coalescent approach to study linkage disequilibrium between single-nucleotide polymorphisms. Am. J. Hum. Genet. 66, 615–628 (2000).
Terwilliger, J.D. & Weiss, K.M. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr. Opin. Biotech. 9, 578–594 (1998).
Terwilliger, J.D. & Goring, H.H. Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design. Hum. Biol. 72, 63–132 (2000).
Terwilliger, J.D. A likelihood-based extended admixture model of oligogenic inheritance in “model-based” or “model-free” analysis. Eur. J. Hum. Genet. (in press).
Göring, H.H. & Terwilliger, J.D. Linkage analysis in the presence of errors. III. Marker loci and their map as nuisance parameters. Am. J. Hum. Genet. 66, 1298–1309 (2000).
Göring, H.H. & Terwilliger, J.D. Linkage analysis in the presence of errors. l V. Joint pseudomarker analysis of linkage and/or linkage disequilibrium on a mixture of pedigrees and singletons when the mode of inheritance cannot be accurately specified. Am. J. Hum. Genet. 66, 1310–1327 (2000).
Heckenlively, J. & Daiger, S. Heredity and retinal and choroidal degenerations. in Emory and Rimoin's Principles and Practice of Medical Genetics (eds Rimoin, D., Connor, J. & Pyeritz, R.) 2555–2576 (Churchill-Livingstone, Edinburgh, 1996).
Terwilliger, J.D. On the resolution and feasibility of genome scanning approaches to unraveling the genetic components of multifactorial phenotypes.l. in Genetic Dissection of Complex Phenotypes: Challenges for the Next Millennium (eds Rao, D.C. & Province, M.A.) (Academic, New York, 2000).
Collins, A., Lonjou, C. & Morton, N.E. Genetic epidemiology of single-nucleotide polymorphisms. Proc. Natl Acad. Sci. USA 96, 15173–15177 (1999).
Schork, N.J., Cardon, L.R. & Xu, X. The future of genetic epidemiology. Trends Genet. 14, 266–272 (1998).
Ott, J. Predicting the range of linkage disequilibrium. Proc. Natl Acad. USA 97, 2–3 (2000).
Weiss, K.M. Genetic Variation and Human Disease: Principles and Evolutionary Approaches (Cambridge University Press, Cambridge, 1999).
Weiss, K. Is there a paradigm shift in genetics? Lessons from the study of human diseases. Mol. Phylogenet. Evol. 5, 259–265 (1996).
Clark, A.G. et al. Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase. Am. J. Hum. Genet. 63, 595–612 (1998).
Nickerson, D.A. et al. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nature Genet. 19, 233–240 (1998).
Templeton, A.R. et al. Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am. J. Hum. Genet. 66, 69–83 (2000).
Sing, C. et al. Genotype-phenotype studies based on the full DNA sequence of the Apo E gene demonstrate the challenge we face in the assignment of function to a particular DNA polymorphism. Am. J. Hum. Genet. 65, A14 (1999).
Roberts, L. Human genome research. SNP mappers confront reality and find it daunting. Science 287, 1898–1899 (2000).
Terwilliger, J.D., Zollner, S., Laan, M. & Paabo, S. Mapping genes through the use of linkage disequilibrium generated by genetic drift: ‘Drift mapping’ in small populations with no demographic expansion. Hum. Hered. 48, 148–154 (1998).
Eaves, I.A. et al. The genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes Nature Genet. 25, 320–323 (2000).
Varilo, T. et al. Linkage disequilibrium in isolated populations: Finland and a young sub-population of Kuusamo. Eur. J. Hum. Genet. 8, 604–612 (2000).
Halushka, M.K. et al. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nature Genet. 22, 239–247 (1999).
Garg, K., Green, P. & Nickerson, D. Identification of candidate coding region single nucleotide polymorphisms in 165 human genes using assembled expressed sequence tags. Genome Res. 9, 1087–1092 (1999).
Picoult-Newberg, L. et al. Mining SNPs from EST databases. Genome Res. 9, 167–174 (1999)-
Irizarry, K. et al. Genome-wide analysis of single-nucleotide polymorphisms in human expressed sequences. Nature Genet. 26, 233–236 (2000).
Beckwith, J. & Zipser, D. (eds) The Lactose Operon (Cold Spring Harbor Laboratory, Cold Spring Harbor, 1970).
Long, A., Lyman, R., Langley, C. & Mackay, T.F. Two sites in the Delta gene region contribute to naturally occurring variation in bristle number in Drosophila melanogaster. Genetics 149, 999–1017 (1998).
Mackay, T.F. The nature of quantitative genetic variation revisited: lessons from Drosophila bristles. Bioessays 18, 113–121 (1996).
Stam, L. & Laurie, C. Molecular dissection of a major gene effect on a quantitative trait: the level of alcohol dehydrogenase expression in Drosophila melanogaster. Genetics 144, 1559–1564 (1996).
Hendrich, Z. & Willard, H. Epigenetic regulation of gene expression—the effect of altered chromatic structure from yeast to mammals. Hum. Mol. Genet. 4, 1765–1777 (1995).
Artiga, M. et al. Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene. Hum. Mol. Genet. 7, 1887–1892 (1998).
Hall, S. et al. A common mutation in the lipoprotein lipase gene promoter, −93T/G, is associated with lower plasma triglyceride levels and increased promoter activity in vitro. Arteriorscler. Thromb. Vasc. Biol. 17, 1969–1976 (1997).
Gragnoli, C. et al. Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4 α binding site in the promoter of the hepatocyte nuclear factor-1 α gene. Diabetes 46, 1648–1651 (1997).
Scholtz, C. et al. Mutation −59C→T in repeat 2 of the LDL receptor promoter: reduction in transcriptional activity and possible allelic interaction in a South African family with familial hypercholesterolemia. Hum. Mol. Genet. 8, 2025–2030 (1999).
Steel, C. Cancer of the breast and female reproductive tract. in Emory and Rimoin's Principles and Practice of Medical Genetics (eds Rimoin, D., Connor, J. & Pyertiz, R.) 1501–1524 (Churchill-Livingstone, Edinburgh, 1996).
Horikawa, Y. et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nature Genet. 26, 163–175 (2000).
Weiss, K. In search of human variation. Genome Res. 8, 691–697 (1998).
Schlichting, C. & Pigliucci, M. Phenotypic Evolution: A Reaction Norm Perspective (Sinauer Associates, Sunderland, 1998).
Weiss, K. & Fullerton, S. Phenogenetic drift and the evolution of genotype-phenotype relationships. Theor. Popul. Biol. (in press).
Waterland, R. & Garza, C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am. J. Clin. Nutr. 69, 179–197 (1999).
Trowell, H. & Burkitt, D. Western Diseases: Their Emergence & Prevention (Harvard University Press, Cambridge, Massachusetts, 1981).
Shephard, R. & Rode, A. The Health Consequences of “Modernization” (Cambridge University Press, Cambridge, UK, 1996).
Anderson, N.L. & Anderson, N.G. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis 19, 1853–1861 (1998).
Brent, R. Functional genomics: Learning to think about gene expression data. Curr. Biol. 9, 338–341 (1999).
Brent, R. Genomic biology. Cell 100, 169–183 (2000).
Schena, M. et al. Microarrays: biotechnology's discovery platform for functional genomics. Trends Biotechnol. 16, 301–306 (1998).
Woychik, R., KIebig, M., Jusice, M., Magnusson, T. & Avrer, E. Functional genomics in the post-genome era. Mut. Res. 400, 3–14 (1998).
Bojko, E. & Larsen, T. Changes in the serum lipid proflie in man during 24 months Arctic residence. Int. J. Circumpolar Health 58, 170–175 (1999).
Bojko, E. Metabolical changes induced by adaptation to circumpolar conditions in Spitzbergen. Int. J. Circumpolar Health 56, 134–141 (1997).
Rowell, L.B. Human Cardiovascular Control (Oxford University Press, Oxford, 1993).
Hatfield, F. & Platz, T. Hardcore Bodybuilding: a Scientific Approach (Contemporary Books, Chicago, 1993).
Schlief, R. Genetics & Molecular Biology (Addison-Wesley, Reading, Massachusetts, 1986).
Cole, K.A., Krizman, D.B. & Emmert-Buck, M.R. The genetics of cancer—a 3D model. Nature Genet. 21, 38–41 (2000).
Ewens, W.J. Tay-Sachs disease and theoretical population genetics. Am. J. Hum. Genet. 30, 328–329 (1978).
Trembath, R. et al. Identification of a major susceptibility locuson chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum. Mol. Genet. 6, 813–820 (1997).
Tang, M.X. et al. Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City. Am. J. Hum. Genet. 58, 574–584 (1996).
Farrer, L.A. et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278, 1349–1356 (1997).
Tang, M. et al. The APOE-epsilon4 allele and the risk of Alzheimer disease among African-Americans, Whites, and Hispanics. JAMA 2789, 751–755 (1998).
Nikali, K. et al. Random search for shared chromosomal regions in four affected individuals. Am. J. Hum. Genet. 56, 1088–1095 (1995).
Martin, E.R. et al. SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in alzheimer disease. Am. J. Hum. Genet. 67, 383–394 (2000).
Martin, E.R. et al. Analysis of association at single nucleotide polymorphisms in the APOE region. Genomics 63, 7–12 (2000).
Bjerregard, P. & Young, T. The Circumpolar Inuit: Health of a Population in Transition (Munksgaard, Copenhagen, 1998).
Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).
McKusick, V.A. Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders (Johns Hopkins University Press, Baltimore, Maryland, 1998).
Sarkar, S. Genetics and Reductionism (Cambridge University Press, Cambridge, UK, 1998).
Support to J.D.T. is acknowledged from a Hitchings-Elion Fellowship from the Burroughs-Wellcome Fund, and to K.M.W. from NIH grant HL 58239. The opinions in this article are the personal views of the authors, and do not necessarily reflect the views or policies of the funders.
About this article
Cite this article
Weiss, K., Terwilliger, J. How many diseases does it take to map a gene with SNPs?. Nat Genet 26, 151–157 (2000). https://doi.org/10.1038/79866
Human Genetics (2020)
The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
Molecular Psychiatry (2018)
Nature Reviews Gastroenterology & Hepatology (2017)
Current Diabetes Reports (2016)
Genome Medicine (2014)