• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. May 2000; 155(1): 421–430.
PMCID: PMC1461086

Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci.

Abstract

A multimarker linkage disequilibrium mapping method was developed for the fine mapping of quantitative trait loci (QTL) using a dense marker map. The method compares the expected covariances between haplotype effects given a postulated QTL position to the covariances that are found in the data. The expected covariances between the haplotype effects are proportional to the probability that the QTL position is identical by descent (IBD) given the marker haplotype information, which is calculated using the genedropping method. Simulation results showed that a QTL was correctly positioned within a region of 3, 1.5, or 0.75 cM in 70, 62, and 68%, respectively, of the replicates using markers spaced at intervals of 1, 0.5, and 0.25 cM, respectively. These results were rather insensitive to the number of generations since the QTL occurred and to the effective population size, except that 10 generations yielded rather poor estimates of the QTL position. The position estimates of this multimarker disequilibrium mapping method were more accurate than those from a single marker transmission disequilibrium test. A general approach for identifying QTL is suggested, where several stages of disequilibrium mapping are used with increasingly dense marker spacing.

Full Text

The Full Text of this article is available as a PDF (128K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hoeschele I, Uimari P, Grignola FE, Zhang Q, Gage KM. Advances in statistical methods to map quantitative trait loci in outbred populations. Genetics. 1997 Nov;147(3):1445–1457. [PMC free article] [PubMed]
  • Houwen RH, Baharloo S, Blankenship K, Raeymaekers P, Juyn J, Sandkuijl LA, Freimer NB. Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis. Nat Genet. 1994 Dec;8(4):380–386. [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]
  • Kaplan NL, Hill WG, Weir BS. Likelihood methods for locating disease genes in nonequilibrium populations. Am J Hum Genet. 1995 Jan;56(1):18–32. [PMC free article] [PubMed]
  • Long AD, Mullaney SL, Reid LA, Fry JD, Langley CH, Mackay TF. High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster. Genetics. 1995 Mar;139(3):1273–1291. [PMC free article] [PubMed]
  • O'Brien SJ, Womack JE, Lyons LA, Moore KJ, Jenkins NA, Copeland NG. Anchored reference loci for comparative genome mapping in mammals. Nat Genet. 1993 Feb;3(2):103–112. [PubMed]
  • Darvasi A, Weinreb A, Minke V, Weller JI, Soller M. Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. Genetics. 1993 Jul;134(3):943–951. [PMC free article] [PubMed]
  • Rabinowitz D. A transmission disequilibrium test for quantitative trait loci. Hum Hered. 1997 Nov-Dec;47(6):342–350. [PubMed]
  • Templeton AR, Boerwinkle E, Sing CF. A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping. I. Basic theory and an analysis of alcohol dehydrogenase activity in Drosophila. Genetics. 1987 Oct;117(2):343–351. [PMC free article] [PubMed]
  • Hästbacka J, de la Chapelle A, Kaitila I, Sistonen P, Weaver A, Lander E. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet. 1992 Nov;2(3):204–211. [PubMed]
  • Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL, et al. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. [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]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles