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:

Population genetics—making sense out of sequence

Nature Genetics volume 21, pages 56–60 (1999)Cite this article

Abstract

The complete human genome nucleotide sequence and technologies for assessing sequence variation on a genome–scale will prompt comprehensive studies of comparative genomic diversity in human populations across the globe. These studies, besides rejuvenating population genetics and our interest in how genetic variation is created and maintained, will provide the intellectual basis for understanding the genetic basis for complex diseases and traits.

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

Figure 1: Competing theories for complex disease inheritance.
Figure 2: The evolutionary origin of polymorphic sites in a genomic segment.

Similar content being viewed by others

References

  1. Collins, F.S. et al. New goals for the U.S. human genome project. Science 282, 682–689 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  2. Venter, J.C. et al. Shotgun sequencing of the human genome. Science 280, 1540–1542 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  3. Collins, F.S. Positional cloning moves from perditional to traditional Nature Genet. 4, 347–350 ( 1995).

    Article  Google Scholar 

  4. Lander, E.S. The new genomics: global views of biology. Science 274, 536–539 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Collins, F.S., Guyer, M.S. & Chakravarti, A. Variations on a theme: cataloging human DNA sequence variation. Science 278, 1580– 1581 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Cavalli–Sforza, L., Menozzi, P. & Piazza, A. The History and Geography of Human Genes (Princeton University Press, Princeton, 1994).

    Google Scholar 

  8. Provine, W.B. The Origins of Theoretical Population Genetics (The University of Chicago Press, Chicago, 1971).

    Google Scholar 

  9. Fisher, R.A. The Genetical Theory of Natural Selection (Clarendon Press, Oxford, 1930).

    Book  Google Scholar 

  10. Haldane, J.B.S. The Causes of Evolution (Longmans and Green, London, 1932).

    Google Scholar 

  11. Wright, S. Evolution and the Genetics of Populations, Volume 2: The Theory of Gene Frequencies (The University of Chicago Press, Chicago, 1997).

    Google Scholar 

  12. Wright, S. Evolution and the Genetics of Populations, Volume 3: Experimental Results and Evolutionary Deductions (The University of Chicago Press, Chicago, 1977).

    Google Scholar 

  13. Wright, S. Evolution and the Genetics of Populations, Volume 3: Variability Within and Among Natural Populations (The University of Chicago Press, Chicago, 1977).

    Google Scholar 

  14. Hacia, J. Resequencing and mutational analysis using oligonucleotide microarrays. Nature Genet. 21, 42–47 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Southern, E. Mir, K. & Shchepinov, M. Molecular interactions on microarrays. Nature Genet. 21, 5–9 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  16. Duggan, D.J., Bittner, M., Chen, Y., Meltzer, P. & Trent, J. Expression profiling using cDNA microarrays. Nature Genet. 21, 10–14 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Lipshutz, R.J., Fodor, S.P.A., Gingeras, T.R. & Lockhart, D.J. High density synthetic oligonucleotide arrays. Nature Genet. 21, 20–24 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Harris, H. Enzyme polymorphisms in man. Proc. Royal Soc. London B 164, 298–310 (1966).

    Article  CAS  Google Scholar 

  19. Nei, M. Molecular Population Genetics and Evolution (North–Holland Publishing Company, Amsterdam, 1975).

    Google Scholar 

  20. Nei, M. Molecular Evolutionary Genetics (Columbia University Press, New York, 1987).

    Google Scholar 

  21. Harpending, H.C. et al. Genetic traces of ancient demography. Proc. Natl. Acad. Sci. USA 95, 1961–1967 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. King, M.C. & Wilson, A.C. Evolution at two levels in humans and chimpanzees. Science 188, 107– 116 (1975).

    Article  CAS  PubMed  Google Scholar 

  23. Jeffreys, A.J. DNA sequence variants in the G gamma–, A gamma–, delta– and beta–globin genes of man. Cell 18, 1–10 (1979).

    Article  CAS  PubMed  Google Scholar 

  24. Chakravarti, A. et al. Nonuniform recombination within the human beta–globin gene cluster. Amer. J. Human Genet. 36, 1239–1258 (1984).

    CAS  Google Scholar 

  25. Li, W.H. & Sadler, L.A. Low nucleotide diversity in man. Genetics 129, 513–523 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ansari–Lari, M.A. et al. The extent of genetic variation in the CCR5 gene. Nature Genet. 16, 221–222 (1997).

    Article  PubMed  Google Scholar 

  27. Angrist, M. et al. Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility. Genomics 48, 354–362 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  28. 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).

    Article  CAS  PubMed  Google Scholar 

  29. Chakravarti, A. It's raining SNPs, hallelujah? Nature Genet. 19, 216–217 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Wang, D.G. et al. Large–scale identification, mapping, and genotyping of single–nucleotide polymorphisms in the human genome. Science 280, 1077–1082 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  31. Kawasaki, K. et al. One–megabase sequence analysis of the human immunoglobulin lambda gene locus. Genome Res. 7, 250– 261 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Eichler, E.E. et al. Duplication of a gene–rich cluster between 16p11.1 and Xq28: a novel pericentromeric–directed mechanism for paralogous genome evolution. Human Mol. Genet. 5, 899– 912 (1996).

    Article  CAS  Google Scholar 

  33. Kimura, M. Stochastic processes and distribution of gene frequencies under natural selection. Cold Spring Harbor Symp. Quant. Biol. 20, 33–53 (1995).

    Article  Google Scholar 

  34. Kimura, M. Evolutionary rate at the molecular level. Nature 217 , 624–626 (1968).

    Article  CAS  PubMed  Google Scholar 

  35. Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983).

    Book  Google Scholar 

  36. Hughes, A.L. & Nei, M. Pattern of nucleotide substitution at major histocompatibility complex class 1 loci reveals overdominant selection. Nature 335, 167–170 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Hudson, R.R. Levels of DNA polymorphism and divergence yield important insights into evolutionary processes. Proc. Natl Acad. Sci. USA 90, 7425–7426 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hacia, J.G. et al. Detection of heterozygous mutations in BRCA1 using high–density oligonucleotide arrays and two–colour fluorescence analysis. Nature Genet. 14, 441– 447 (1996).

    Article  CAS  PubMed  Google Scholar 

  39. Halushka, M. et al. Analysis of gene variation within and between humans and primates using high–density olligonucleotide arrays. in: Genome Mapping, Sequencing and Biology (Cold Spring Harbor, New York, 1998).

    Google Scholar 

  40. Seielstad, M.T., Minch, E. & Cavalli–Sforza, L.L. Genetic evidence for a higher female migration rate in humans. Nature Genet. 20, 278–280 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Lewontin, R.C. The apportionment of human diversity. Evol. Biol. 6 , 381–398 (1972).

    Google Scholar 

  42. Nei, M. & Roychoudhury, A.K. Gene differences between Caucasian, Negro, and Japanese populations. Science 177, 434–436 (1972).

    Article  CAS  PubMed  Google Scholar 

  43. Vigilant, L. et al. African populations and the evolution of human mitochondrial DNA. Science 253, 1503– 1507 (1991).

    Article  CAS  PubMed  Google Scholar 

  44. Kerem, B. et al. Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073–1080 (1989).

    Article  CAS  PubMed  Google Scholar 

  45. Smith, M.W. et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV–1 infection and disease progression. Science 277, 959–965 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Juengst, E.T. Groups as gatekeepers to genomic research: Conceptually confusing, morally hazardous, and practically useless. J. Kennedy Inst. Ethics 8, 183–200 (1998).

    Article  Google Scholar 

  47. Committee on Human Genome Diversity, National Research council. Evaluating Human Genetic Diversity (National Academy Press, Washington, 1997).

  48. McKusick, V.A. Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders (12th edition)(Johns Hopkins University Press, Baltimore, 1998).

    Google Scholar 

  49. Lander, E.S. & Schork, N.J. Genetic dissection of complex traits. Science 265, 2037–2048 (1994).

    Article  CAS  PubMed  Google Scholar 

  50. de la Chapelle, A. & Wright, F.A. Linkage disequilibrium mapping in isolated populations: the example of Finland revisited. Proc. Natl Acad. Sci. USA 95, 16–23 (1998).

    Article  Google Scholar 

  51. Jorde, L.B. Linkage disequilibrium as a gene–mapping tool. Amer. J. Human Genet. 56, 11–14 ( 1995).

    CAS  Google Scholar 

  52. Clark, A.G. et al. Haplotype structure and population genetic inferences from nucleotide–sequence variation in human lipoprotein lipase. Amer. J. Human Genet. 63, 595–612 (1998).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, 44106, Ohio, USA

    Aravinda Chakravarti

Authors
  1. Aravinda Chakravarti
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chakravarti, A. Population genetics—making sense out of sequence. Nat Genet 21 (Suppl 1), 56–60 (1999). https://doi.org/10.1038/4482

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/4482

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