Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Use of population isolates for mapping complex traits

Nature Reviews Genetics volume 1, pages 182–190 (2000)Cite this article

Abstract

Geneticists have repeatedly turned to population isolates for mapping and cloning Mendelian disease genes. Population isolates possess many advantages in this regard. Foremost among these is the tendency for affected individuals to share ancestral haplotypes derived from a handful of founders. These haplotype signatures have guided scientists in the fine mapping of scores of rare disease genes. The past successes with Mendelian disorders using population isolates have prompted unprecedented interest among medical researchers in both the public and private sectors. Despite the obvious genetic and environmental complications, geneticists have targeted several population isolates for mapping genes for complex diseases.

Key Points

  • Genetic isolates have proved very valuable for mapping and positionally cloning rare recessive diseases. Recently, however, the use of isolates in genetic studies of complex traits has been challenged.

  • Isolates differ not only in their demographic histories and characteristic genetic diseases but also in their health-care standards and availability of geneological and patient records. Researchers should be mindful of these differences in designing genetic studies.

  • Young population isolates are best for coarse haplotype mapping, and older isolates and outbred populations are best for fine haplotype mapping and final gene identification.

  • Isolated populations have the advantage of reduced environmental (and diagnostic) heterogeneity, as well as of reduced genetic heterogeneity.

  • Most successes in mapping complex trait loci in isolates have used genome-wide linkage analyses of large families with multiple affected individuals.

  • Rare Mendelian variants of complex disease, potentially enriched in isolates, offer precious insights into the pathology of complex disease.

  • The rapid development of SNP maps and SNP genotyping technologies is opening new avenues to the identification of shared haplotype signatures among affected individuals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Puffenberger, E. G. et al. Identity-by-descent and association mapping of a recessive gene for Hirschspring disease on human chromosome 13q22. Hum. Mol. Genet. 3, 1217–1225 ( 1994).

    Article  CAS  PubMed  Google Scholar 

  2. Puffenberger, E. G. et al. A missense mutation of the Endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell 79, 1257– 1266 (1994).References 1 and 2 provide an early, beautiful example of how a complex disease can become a simple disease and how a population isolate can be used to dissect a phenotype.

    Article  CAS  PubMed  Google Scholar 

  3. Scott D. A. et al. Nonsyndromic autosomal recessive deafness is linked to the DFNBI locus in a large inbred Bedouin family from Israel. Am. J. Hum. Genet. 57, 965–968 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bollobas, B. Littlewood's Miscellany (Cambridge Univ. Press, Cambridge, 1988).

    Google Scholar 

  5. Cavalli-Sforza, L. The DNA revolution in population genetics. Trends Genet. 14, 60–65 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Kidd, J. R. et al. Haplotypes and linkage disequilibrium at the phenylalanine hydroxylase locus, PAH, in a global, MH representation of populations. Am. J. Hum. Genet. 66, 1882–1899 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sajantila, A. et al. Paternal and maternal linkages reveal a bottleneck in the founding of the Finnish population. Proc. Natl Acad. Sci. USA 93, 12035–12039 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kittles, R. A. et al. Dual origins of Finns revealed by Y chromosome haplotype variation . Am. J. Hum. Genet. 62, 1171– 1179 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. de la Chapelle, A & Wright F. A. Linkage disequilibrium mapping in isolate populations: The example of Finland revisited. Proc. Natl Acad. Sci. USA 95, 12416– 12423 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jorde, L. B. et al. Gene mapping in isolated populations: New roles for old friends? Hum. Hered. 50, 57–65 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Varilo, T. et al. Linkage disequilibrium in isolated populations: Finland and a young sub–population of Kuusamo. Eur. J. Hum. Genet. (in the press).

  12. Terwilliger, J. D., Zöllner, S., Laan, M. & Pääbo, S. Mapping in small populations with no demographic expansion. Hum. Hered. 48, 138–154 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  13. Peltonen, L. Positional cloning of disease genes: Advantages of genetic isolates. Hum. Hered. 50, 66–75 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  14. Peltonen, L., Jalanko, A. & Varilo, T. Molecular genetics of the Finnish disease heritage. Hum. Mol. Genet. 8, 1913–1923 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Wright, A. F., Carothers, A. D. & Pirastu, M. Population choice in mapping genes for complex diseases . Nature Genet. 23, 397– 404 (1999).Considers in some detail the advantages and disadvantages of various populations in mapping common disease genes.

    Article  CAS  PubMed  Google Scholar 

  16. Houwen, R. H. et al. Genome screening by searching for shared segments: Mapping a gene for benign recurrent intrahepatic cholestasis. Nature Genet. 8, 380–386 ( 1994).Shows the power of the founder effect and population isolation in the search for a disease gene. Scanning for a haplotype signature in affected individuals can be used to localize the gene.

    Article  CAS  PubMed  Google Scholar 

  17. Nikali, K. et al. Random search for shared chromosomal regions: the assignment of a new hereditary ataxia locus. Am. J. Hum. Genet. 56, 1088–1095 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Peltomaki, P. et al. Genetic mapping of a locus predisposing to human colorectal cancer. Science 260, 810– 812 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Pajukanta, P. et al. Linkage of familial combined hyperlipidaemia to chromosome 1q21–q23. Nature Genet. 18, 369– 373 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Hanson, R. L. et al. An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am. J. Hum. Genet. 63, 1130–1138 ( 1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Collins, F. S., Guyer, M. S. & Charkravarti, A. Variations on a theme: cataloguing human DNA sequence variation. Science 278, 1580– 1581 (1997).Lays out the rationale for the discovery and application of single nucleotide polymorphisms.

    Article  CAS  PubMed  Google Scholar 

  22. Kruglyak, L. Prospect for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet. 22, 139– 144 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Zwick, M. E. et al. Characterizing human genomic variation and linkage disequililibrium in multiple 100kb genomic segments using large-scale, microarray–based SNP detection. Am. J. Hum. Genet. 67, S22 (2000).

    Google Scholar 

  24. 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).Explores one human gene intensely for polymorphisms and linkage disequilibrium. This type of study is a forerunner of what will be done on a genome-wide basis.

    Article  CAS  PubMed  Google Scholar 

  25. 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).

    Article  CAS  PubMed  Google Scholar 

  26. Taillon-Miller, P. et al. Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nature Genet. 25, 324–328 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Moehlke, K. L. et al. Marker–marker linkage disequilibrium extends beyond 1 cM on chromosome 20 in Finns. Am. J. Human Genet. 67, S25 (2000).

    Google Scholar 

  28. Greenberg, D. A., Abreu, P. & Hodge, S. E. The power to detect linkage in complex disease by means of simple LOD-score analyses. Am. J. Hum. Genet. 63 , 870–879 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Clerget-Darpoux, F., Bonaiti-Pellie, C. & Hochez, J. Effects of misspecifying genetic parameters in lod score analysis. Biometrics 42, 393– 399 (1986).

    Article  CAS  PubMed  Google Scholar 

  30. Kruglyak, L., Daly, M. J., Reeve-Daly, M. P. & Lander, E. S. Parametric and nonparametric linkage analysis: A unified multipoint approach . Am. J. Hum. Genet. 58, 1347– 1363 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Sobel, E. & Lange, K. Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker sharing statistics . Am. J. Hum. Genet. 58, 1323– 1337 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Abreu, P. C., Greenberg, D. A. & Hodge, S. E. Direct power comparisons between simple lod scores and NPL scores for linkage analysis in complex diseases. Am. J. Hum. Genet. 65, 847–857 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996). Argues the case for association studies over linkage studies.

    Article  CAS  PubMed  Google Scholar 

  34. Terwilliger, J. D. & Ott, J. A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. Hum. Hered. 42, 337–346 (1992).

    Article  CAS  PubMed  Google Scholar 

  35. Spielman, R. S., McGinnis, R. E. & Ewens, W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–516 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Allison, D. B., Heo, M., Kaplan, N. & Martin, E. R. Sibling–based tests of linkage and association for quantitative traits. Am. J. Hum. Genet. 64, 1754–1763 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Boehnke, M. & Langefeld, C. D. Genetic association mapping based on discordant sib pairs: the discordant-alleles test. Am. J. Hum. Genet. 62, 950–961 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Spielman, R. S. & Ewens, W. J. A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am. J. Hum. Genet. 62, 450– 458 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schaid, D. J. & Rowland, C. Use of parents, sibs, and unrelated controls for detection of associations between genetic markers and disease . Am. J. Hum. Genet. 63, 1492– 1506 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Teng, J. & Risch, N. The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping. Genome Res. 9, 234–241 (1999).

    CAS  PubMed  Google Scholar 

  41. Sinsheimer, J. S., Blangero, J. & Lange, K. Gamete competition models. Am. J. Hum. Genet. 66, 1168–1172 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Collins, A. & Morton, N. E. Mapping a disease locus by allelic association. Proc. Natl Acad. Sci. USA 95, 1741–1745 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Devlin, B., Risch, N. & Roeder, K. Disequilibrium mapping: composite likelihood for pairwise disequilibrium. Genomics 36, 1– 16 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Kaplan, N. L. Hill, W. G. & Weir, B. S. Likelihood methods for locating disease genes in non-equilibrium populations. Am. J. Hum. Genet. 56, 18– 32 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lazzeroni, L. C. & Lange, K. A conditional inference framework for extending the transmission/disequilibrium test. Hum. Hered. 48, 67–81 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  46. McPeek, M. S. & Strahs, A. Assessment of linkage disequilibrium by the decay of haplotype sharing, with application to fine scale genetic mapping. Am. J. Hum. Genet. 65, 858– 875 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rannala, B. & Slatkin, M. Likelihood analysis of disequilibrium mapping, and related problems. Am. J. Hum. Genet. 62 , 459–473 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Terwilliger, J. D. A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. Am. J. Hum. Genet. 56, 777–787 ( 1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Xiong, M. & Guo, S. W. Fine-scale genetic mapping based on linkage disequilibrium: theory and applications. Am. J. Hum. Genet. 60, 1513–1531 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Göring, H. H. H. & Terwilliger, J. D. Linkage analysis in the presence of errors IV: 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).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Leach, F. S. et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75, 1215– 1225 (1993).

    Article  CAS  PubMed  Google Scholar 

  52. Bronner, C. E. et al. Mutation in the DNA mismatch pair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368, 258–261 (1994).

    Article  CAS  PubMed  Google Scholar 

  53. Sheffield, V. C., Stone, E. M. & Carmi, R. Use of isolated inbred human populations for identification of disease genes. Trends Genet. 14, 391– 396 (1998).

    Article  CAS  PubMed  Google Scholar 

  54. Kuokkanen, S. et al. Genome wide scan of multiple sclerosis in Finnish multiplex families. Am. J. Hum. Genet. 61, 1379– 1387 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chataway, J. et al. The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. Brain 121, 1869–1887 ( 1998).

    Article  PubMed  Google Scholar 

  56. Castellani, L. W. et al. Mapping a gene for combined hyperlipidemia in a mutant mouse strain. Nature Genet. 18, 374– 377 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. Pei, W. et al. Support for linkage of familial combined hyperlipidemia to chromosome 1q21–q23 in Chinese and German families. Clin. Genet. 57, 29–34 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Pajukanta, P. et al. Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels. Am. J. Hum. Genet. 64, 1453–1463 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Almasy, L. & Blangero, J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62 , 1198–1211 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Amos, C. I. Robust variance-components approach for assessing genetic linkage in pedigrees . Am. J. Hum. Genet. 54, 535– 543 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Blangero, J. & Almasy, L. Multipoint oligenic linkage analysis of quantitative traits. Genet. Epidemiol. 14, 959–964 (1997).

    Article  CAS  PubMed  Google Scholar 

  62. Goldar, D. E. Multipoint analysis of human quantitative genetic variation. Am. J. Hum. Genet. 47, 957–967 (1990).

    Google Scholar 

  63. Hoppers, J. L. & Mathews, J. D. Extensions to multivariate normal models for pedigree analysis. Ann. Hum. Genet. 46, 373–383 ( 1982).

    Article  Google Scholar 

  64. Schork, N. J. Extended multipoint identity-by-descent analysis of human quantitative traits: efficiency, power, and modeling considerations. Am. J. Hum. Genet. 53, 1306–1319 ( 1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Frary, A. et al. fw2.2: A quantitative trait locus key to the evolution of tomato fruit size. Science 289, 85– 88 (2000).A landmark publication reporting the isolation of a quantitative trait locus gene by positional cloning.

    Article  CAS  PubMed  Google Scholar 

  66. Varilo, T. et al. Linkage disequilibrium in isolated populations: Finland and a young subpopulation of Kuusamo. Eur. J. Hum. Genet. (in the press).

  67. Helgason, A. et al. Estimating Scandinavian and Gaelic ancestry in the male settlers of Iceland. Am. J. Hum. Genet. 67, 697– 717 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ginns, E. I. et al. A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish. Nature Genet. 12, 431–435 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. Detera-Wadleigh, S. et al. A high-density genome scan detects evidence for a biopolar–disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2 . Proc. Natl Acad. Sci. USA 96, 5604– 5609 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ober, C. et al. Collaborative study on the genetics of asthma. Genome-wide search for asthma susceptibility loci in a founder population. Hum. Mol. Genet. 7, 1393–1398 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  71. Ober, C., Tsalenko, A., Parry, R. & Cox, N. J. A second-generation genomewide screen for asthma-suspectibility alleles in a founder population Am. J. Hum. Genet. 67, 1154– 1162 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Marsh, D. G. et al. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nature Genet. 15, 389 –392 (1997).

    Article  Google Scholar 

  73. Hanson, R. L. et al. An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am. J. Hum. Genet. 63, 1130–1138 ( 1998).Shows the power of the quantitative trait locus strategy and the quantitation of phenotypes for the identification of disease susceptibility loci.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Elbein, S., Hoffman, M., Teng, K., Leppert, M. & Hasstect, S. A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. Diabetes 48, 1175 –1182 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Ghosh, S. et al. The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to Type 2 diabetes. Am. J. Hum. Genet. 67, 1174–1185 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Guilford, P. et al. A non–syndromic form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q. Nature Genet. 6, 24–28 (1994 ).

    Article  CAS  PubMed  Google Scholar 

  77. Scott, D. A. et al. Nonsyndromic autosomal recessive deafness is linked to the DFNBI locus in a large inbred Bedouin family from Israel. Am. J. Hum. Genet. 57, 965–968 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Kelsell, D.P. et al. Connexin 26 mutations in hereditary nonsyndromic sensorineural deafness. Nature 387, 80– 83 (1997).

    Article  CAS  PubMed  Google Scholar 

  79. Hovatta, I. et al. A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation suggesting multiple susceptibility loci. Am. J. Hum. Genet. 65, 1114–1124 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Brzustowicz, L. M., Hodgkinson, K. A., Chow, E. W. C., Honer, W. G. & Bassett A. S. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21–q22 . Science 288, 678–682 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kuokkanen, S. et al. A putative vulnerability locus to multiple sclerosis maps to 5p14–p12 in a region syntenic to the murine locus Eae2. Nature Genet. 13, 477–480 (1996).

    Article  CAS  PubMed  Google Scholar 

  82. Sawcer, S. et al. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nature Genet. 13 , 444–468 (1996).

    Article  Google Scholar 

  83. Castellani, L. W. et al. Mapping a gene for combined hyperlipidemia in a mutant mouse strain. Nature Genet. 18, 374– 377 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Pei, W. et al. Support for linkage of familial combined hyperlipidemia to chromosome 1q21–q23 in Chinese and German families. Clin. Genet. 57, 29–34 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Moises, H. W. et al. An international two-stage genome-wide search for schizophrenia susceptibility genes. Nature Genet. 11, 321–324 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. Straub, R. E. et al. A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity. Nature Genet. 11, 287–293 ( 1995).

    Article  CAS  PubMed  Google Scholar 

  87. Levinson, D. F. et al. Genome scan of schizophrenia. Am. J. Psychiatry 155, 741–750 ( 1998).

    CAS  PubMed  Google Scholar 

  88. Smith, J. R. et al. Major suscpetibility locus for prostate cancer on chromosome 1 suggested by a genome wide search. Science 274, 1371–1374 (1996).

    Article  CAS  PubMed  Google Scholar 

  89. Berthon, P. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2–43. Am. J. Hum. Genet. 62, 1416–1424 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Xu, J. et al. Combined analysis of hereditary prostate cancer linkage to 1q24–25. Results from 772 hereditary prostate cancer families from the International Consortium for Prostate Cancer Genetics. Am. J. Hum. Genet. 66, 945–957 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Our research has been supported by grants from the National Institutes of Health and an award to the Centre of Excellence in Disease Genetics by the Academy of Finland.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, University of Helsinki and National Public Health Institute, Finland

    Leena Peltonen, Aarno Palotie & Kenneth Lange

  2. Department of Human Genetics, University of California at Los Angeles School of Medicine, California, 90095 , USA

    Leena Peltonen

  3. Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, California, 90095, USA

    Aarno Palotie

  4. Department of Biomathematics, University of California at Los Angeles School of Medicine, California, 90095 , USA

    Kenneth Lange

Authors
  1. Leena Peltonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aarno Palotie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Related links

Related links

DATABASE LINKS

Hirschsprung disease

nonsyndromic hearing loss

nonpolypotic colon cancer

combined hyperlipidaemia

Marfan syndrome

Huntington disease

BRCA1

BRCA2

Bardet–Biedl syndrome

Alzheimer disease

FURTHER INFORMATION

Human Genome Project

deCODE project

The SNP consortium

Glossary

MENDELIAN VARIANT

An individual phenotype that is due to a single gene.

POPULATION BOTTLENECK

A marked reduction in population size followed by the survival and expansion of a small random sample of the original population.

GENETIC DRIFT

The random fluctuation in allele frequencies as genes are transmitted from one generation to the next.

HAPLOTYPE SIGNATURE

The haplotype surrounding a particular disease susceptibility allele. The haplotype signature can be identified among the affected individuals of an isolated population.

TRANSMISSION DISTORTION

Over or under transmission of certain alleles to affected individuals.

ASSOCIATION TESTING

A statistical approach that tests for association between marker or candidate gene alleles and diseases.

POPULATION STRATIFICATION

Subdivision of a population into different ethnic groups with potentially different marker allele frequencies and different disease prevalences.

CONTINGENCY TABLE

A table or matrix to count the numbers of observations falling into various categories. Each category is classified on the basis of several factors.

GAMETE COMPETITION MODEL

A statistical model that views transmission of marker alleles to affected children as a contest between the alleles. Each allele is ranked much as competing teams are ranked in a sports league.

UNASCERTAINED SAMPLE

A sample selected without regard to disease status.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peltonen, L., Palotie, A. & Lange, K. Use of population isolates for mapping complex traits. Nat Rev Genet 1, 182–190 (2000). https://doi.org/10.1038/35042049

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35042049

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing