Frontiers in Biology

, Volume 5, Issue 4, pp 348–353 | Cite as

The Hardy-Weinberg principle and its applications in modern population genetics

  • John J. ChenEmail author


The discovery of the Hardy-Weinberg principle marked the beginning of the field of population genetics. Over the past hundred years, it has provided a starting point for many population genetic investigations. In this review, the Hardy-Weinberg principle, its statistical testing, and several of its applications in various modern population genetic research areas, including allelic variability and selection in the human leukocyte antigen region, microsatellite genotyping error detection, and accuracy of haplotype estimation, are discussed.


the Hardy-Weinberg principle statistical testing population genetics human leukocyte antigens microsatellite genotyping haplotype estimation 


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  1. Chen J J, Duan T, Single R, Mather K, Thomson G (2005). Hardy-Weinberg testing of a single homozygous genotype. Genetics, 170(3): 1439–1442CrossRefPubMedGoogle Scholar
  2. Chen J J, Hollenbach J A, Trachtenberg E A, Just J J, Carrington M, Rønningen K S, Begovich A, King M C, McWeeney S, Mack S J, Erlich H A, Thomson G (1999). Hardy-Weinberg testing for HLA class II (DRB1, DQA1, DQB1, and DPB1) loci in 26 human ethnic groups. Tissue Antigens, 54(6): 533–542CrossRefPubMedGoogle Scholar
  3. Chen J J, Thomson G (1999). The variance for the disequilibrium coefficient in the individual Hardy-Weinberg test. Biometrics, 55(4): 1269–1272CrossRefPubMedGoogle Scholar
  4. Crow J F (1988). Eighty years ago: the beginnings of population genetics. Genetics, 119(3): 473–476PubMedGoogle Scholar
  5. Demers D B, Curry E T, Egholm M, Sozer A C (1995). Enhanced PCR amplification of VNTR locus D1S80 using peptide nucleic acid (PNA). Nucl Acids Res, 23(15): 3050–3055CrossRefPubMedGoogle Scholar
  6. Dempster A P, Laird NM, Rubin D B (1977). Maximum likelihood from incomplete data via EM algorithm. J R Stat Soc, B, 39: 1–38Google Scholar
  7. Ellegren H (2000). Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet, 24(4): 400–402CrossRefPubMedGoogle Scholar
  8. Ellegren H (2004). Microsatellites: simple sequences with complex evolution. Nat Rev Genet, 5(6): 435–445CrossRefPubMedGoogle Scholar
  9. Elston R C, Forthofer R (1977). Testing for Hardy-Weinberg equilibrium in small samples. Biometrics, 33(3): 536–542CrossRefGoogle Scholar
  10. Emigh T H (1980). A comparison of tests for Hardy-Weinberg equilibrium. Biometrics, 36(4): 627–642CrossRefGoogle Scholar
  11. Epstein M P, Satten G A (2003). Inference on haplotype effects in casecontrol studies using unphased genotype data. Am J Hum Genet, 73(6): 1316–1329CrossRefPubMedGoogle Scholar
  12. Excoffier L, Laval G, Schneider S (2005). Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online, 1: 47–50PubMedGoogle Scholar
  13. Excoffier L, Slatkin M (1995). Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol, 12(5): 921–927PubMedGoogle Scholar
  14. Fallin D, Schork N J (2000). Accuracy of haplotype frequency estimation for biallelic loci, via the expectation-maximization algorithm for unphased diploid genotype data. Am J Hum Genet, 67(4): 947–959CrossRefPubMedGoogle Scholar
  15. Gomes I, Collins A, Lonjou C, Thomas N S, Wilkinson J, Watson M, Morton N (1999). Hardy-Weinberg quality control. Ann Hum Genet, 63(Pt 6): 535–538CrossRefPubMedGoogle Scholar
  16. Guo S W, Thompson E A (1992). Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics, 48(2): 361–372CrossRefPubMedGoogle Scholar
  17. Hardy G H (1908). Mendelian proportions in a mixed population. Science, 28(706): 49–50CrossRefPubMedGoogle Scholar
  18. Hearne C M, Ghosh S, Todd J A (1992). Microsatellites for linkage analysis of genetic traits. Trends Genet, 8(8): 288–294CrossRefPubMedGoogle Scholar
  19. Hernández J L, Weir B S (1989). A disequilibrium coefficient approach to Hardy-Weinberg testing. Biometrics, 45(1): 53–70CrossRefPubMedGoogle Scholar
  20. Hosking L, Lumsden S, Lewis K, Yeo A, McCarthy L, Bansal A, Riley J, Purvis I, Xu C F (2004). Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet, 12(5): 395–399CrossRefPubMedGoogle Scholar
  21. Lancaster A K, Single R M, Solberg O D, Nelson M P, Thomson G (2007). PyPop update—a software pipeline for large-scale multilocus population genomics. Tissue Antigens, 69(Suppl 1): 192–197CrossRefPubMedGoogle Scholar
  22. Li C C (1955). Population Genetics. Chicago: University of Chicago PressGoogle Scholar
  23. Louis E J, Dempster E R (1987). An exact test for Hardy-Weinberg and multiple alleles. Biometrics, 43(4): 805–811CrossRefPubMedGoogle Scholar
  24. Meng X L, Rubin D B (1993). Mximum-likelihood estimation via the ECM algorithm — a general framework. Biometrika, 80(2): 267–278CrossRefGoogle Scholar
  25. Miller K M, Kaukinen K H, Beacham T D, Withler R E (2001). Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon. Genetica, 111(1–3): 237–257CrossRefPubMedGoogle Scholar
  26. Morin P A, Leduc R G, Archer F I, Martien K K, Huebinger R, Bickham JW, Taylor B L (2009). Significant deviations from Hardy-Weinberg equilibrium caused by low levels of microsatellite genotyping errors. Molecular Ecology Resources, 9(2): 498–504CrossRefGoogle Scholar
  27. Parham P (2005). MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol, 5(3): 201–214CrossRefPubMedGoogle Scholar
  28. Robinson J, Waller M J, Fail S C, McWilliam H, Lopez R, Parham P, Marsh S G E (2009). The IMGT/HLA database. Nucl Acids Res, 37(SI): D1013–D1017CrossRefPubMedGoogle Scholar
  29. Rodríguez S, Visedo G, Zapata C (2001). Detection of errors in dinucleotide repeat typing by nondenaturing electrophoresis. Electrophoresis, 22(13): 2656–2664CrossRefPubMedGoogle Scholar
  30. Rousset F, Raymond M (1995). Testing heterozygote excess and deficiency. Genetics, 140(4): 1413–1419PubMedGoogle Scholar
  31. Schaid D J (2004). Evaluating associations of haplotypes with traits. Genet Epidemiol, 27(4): 348–364CrossRefPubMedGoogle Scholar
  32. Shoemaker J, Painter I, Weir B S (1998). A Bayesian characterization of Hardy-Weinberg disequilibrium. Genetics, 149(4): 2079–2088PubMedGoogle Scholar
  33. Single R M, Meyer D, Hollenbach J, Nelson M, Noble J A, Erlich H A, Thomson G (2002). Haplotype frequency estimation in patient populations: an example from the HLA region. Genet Epidemiol, 22: 186–195CrossRefPubMedGoogle Scholar
  34. Smith C A B (1986). Chi-squared tests with small numbers. Ann Hum Genet, 50(Pt 2): 163–167CrossRefPubMedGoogle Scholar
  35. Solberg O D, Mack S J, Lancaster A K, Single R M, Tsai Y, Sanchez-Mazas A, Thomson G (2008). Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. Hum Immunol, 69(7): 443–464CrossRefPubMedGoogle Scholar
  36. Takahata N, Satta Y, Klein J (1992). Polymorphism and balancing selection at major histocompatibility complex loci. Genetics, 130(4): 925–938PubMedGoogle Scholar
  37. Trachtenberg E, Korber B, Sollars C, Kepler T B, Hraber P T, Hayes E, Funkhouser R, Fugate M, Theiler J, Hsu Y S, Kunstman K, Wu S, Phair J, Erlich H, Wolinsky S (2003). Advantage of rare HLA supertype in HIV disease progression. Nat Med, 9(7): 928–935CrossRefPubMedGoogle Scholar
  38. Traherne J A (2008). Human MHC architecture and evolution: implications for disease association studies. Int J Immunogenet, 35(3): 179–192CrossRefPubMedGoogle Scholar
  39. Weinberg W(1908). Über den Nachweis der Vererbung beim Menschen. Jahresh. Ver. Vaterl. Naturkd. Württemb, 64: 369–382. On the demonstration of heredity in man (Translated by S.H. Boyer, 1963)Google Scholar
  40. Westfall P H, Young S S (1993). Resampling-based multiple testing. New York: WileyGoogle Scholar

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of Preventive MedicineState University of New York at Stony BrookStony BrookUSA

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