Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. 2001 Dec; 159(4): 1805–1817.
PMCID: PMC1461925

Two-locus sampling distributions and their application.


Methods of estimating two-locus sample probabilities under a neutral model are extended in several ways. Estimation of sample probabilities is described when the ancestral or derived status of each allele is specified. In addition, probabilities for two-locus diploid samples are provided. A method for using these two-locus probabilities to test whether an observed level of linkage disequilibrium is unusually large or small is described. In addition, properties of a maximum-likelihood estimator of the recombination parameter based on independent linked pairs of sites are obtained. A composite-likelihood estimator, for more than two linked sites, is also examined and found to work as well, or better, than other available ad hoc estimators. Linkage disequilibrium in the Xq28 and Xq25 region of humans is analyzed in a sample of Europeans (CEPH). The estimated recombination parameter is about five times smaller than one would expect under an equilibrium neutral model.

Full Text

The Full Text of this article is available as a PDF (171K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andolfatto P, Nordborg M. The effect of gene conversion on intralocus associations. Genetics. 1998 Mar;148(3):1397–1399. [PMC free article] [PubMed]
  • Chakravarti A, Buetow KH, Antonarakis SE, Waber PG, Boehm CD, Kazazian HH. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet. 1984 Nov;36(6):1239–1258. [PMC free article] [PubMed]
  • Ewens WJ. The sampling theory of selectively neutral alleles. Theor Popul Biol. 1972 Mar;3(1):87–112. [PubMed]
  • Frisse L, Hudson RR, Bartoszewicz A, Wall JD, Donfack J, Di Rienzo A. Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am J Hum Genet. 2001 Oct;69(4):831–843. [PMC free article] [PubMed]
  • Golding GB. The sampling distribution of linkage disequilibrium. Genetics. 1984 Sep;108(1):257–274. [PMC free article] [PubMed]
  • Griffiths RC, Marjoram P. Ancestral inference from samples of DNA sequences with recombination. J Comput Biol. 1996 Winter;3(4):479–502. [PubMed]
  • Hey J, Wakeley J. A coalescent estimator of the population recombination rate. Genetics. 1997 Mar;145(3):833–846. [PMC free article] [PubMed]
  • Hill WG. Linkage disequilibrium among multiple neutral alleles produced by mutation in finite population. Theor Popul Biol. 1975 Oct;8(2):117–126. [PubMed]
  • Hill WG, Weir BS. Maximum-likelihood estimation of gene location by linkage disequilibrium. Am J Hum Genet. 1994 Apr;54(4):705–714. [PMC free article] [PubMed]
  • Hudson RR. Properties of a neutral allele model with intragenic recombination. Theor Popul Biol. 1983 Apr;23(2):183–201. [PubMed]
  • Hudson RR. The sampling distribution of linkage disequilibrium under an infinite allele model without selection. Genetics. 1985 Mar;109(3):611–631. [PMC free article] [PubMed]
  • Hudson RR. Estimating the recombination parameter of a finite population model without selection. Genet Res. 1987 Dec;50(3):245–250. [PubMed]
  • Macpherson JN, Weir BS, Leigh Brown AJ. Extensive linkage disequilibrium in the achaete-scute complex of Drosophila melanogaster. Genetics. 1990 Sep;126(1):121–129. [PMC free article] [PubMed]
  • Nielsen R. Estimation of population parameters and recombination rates from single nucleotide polymorphisms. Genetics. 2000 Feb;154(2):931–942. [PMC free article] [PubMed]
  • Kuhner MK, Yamato J, Felsenstein J. Maximum likelihood estimation of recombination rates from population data. Genetics. 2000 Nov;156(3):1393–1401. [PMC free article] [PubMed]
  • Ohta T, Kimura M. Linkage disequilibrium between two segregating nucleotide sites under the steady flux of mutations in a finite population. Genetics. 1971 Aug;68(4):571–580. [PMC free article] [PubMed]
  • Langley CH, Tobari YN, Kojima KI. Linkage disequilibrium in natural populations of Drosophila melanogaster. Genetics. 1974 Nov;78(3):921–936. [PMC free article] [PubMed]
  • Taillon-Miller P, Bauer-Sardiña I, Saccone NL, Putzel J, Laitinen T, Cao A, Kere J, Pilia G, Rice JP, Kwok PY. Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nat Genet. 2000 Jul;25(3):324–328. [PubMed]
  • Langley CH, Lazzaro BP, Phillips W, Heikkinen E, Braverman JM. Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome. Genetics. 2000 Dec;156(4):1837–1852. [PMC free article] [PubMed]
  • Vieira J, Charlesworth B. Evidence for selection at the fused locus of Drosophila virilis. Genetics. 2000 Aug;155(4):1701–1709. [PMC free article] [PubMed]
  • Lewontin RC. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics. 1964 Jan;49(1):49–67. [PMC free article] [PubMed]
  • Wall JD. A comparison of estimators of the population recombination rate. Mol Biol Evol. 2000 Jan;17(1):156–163. [PubMed]
  • Lewontin RC. The detection of linkage disequilibrium in molecular sequence data. Genetics. 1995 May;140(1):377–388. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...