Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. May 2002; 161(1): 275–287.
PMCID: PMC1462117

Simultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14.


A maximum-likelihood QTL mapping method that simultaneously exploits linkage and linkage disequilibrium and that is applicable in outbred half-sib pedigrees is described. The method is applied to fine map a QTL with major effect on milk fat content in a 3-cM marker interval on proximal BTA14. This proximal location is confirmed by applying a haplotype-based association method referred to as recombinant ancestral haplotype analysis. The origin of the discrepancy between the QTL position derived in this work and that of a previous analysis is examined and shown to be due to the existence of distinct marker haplotypes associated with QTL alleles having large substitution effects.

Full Text

The Full Text of this article is available as a PDF (703K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kappes SM, Keele JW, Stone RT, McGraw RA, Sonstegard TS, Smith TP, Lopez-Corrales NL, Beattie CW. A second-generation linkage map of the bovine genome. Genome Res. 1997 Mar;7(3):235–249. [PubMed]
  • Kruglyak L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet. 1999 Jun;22(2):139–144. [PubMed]
  • Lander ES, Schork NJ. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. [PubMed]
  • Looft C, Reinsch N, Karall-Albrecht C, Paul S, Brink M, Thomsen H, Brockmann G, Kühn C, Schwerin M, Kalm E. A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14. Mamm Genome. 2001 Aug;12(8):646–650. [PubMed]
  • Mauricio R. Mapping quantitative trait loci in plants: uses and caveats for evolutionary biology. Nat Rev Genet. 2001 May;2(5):370–381. [PubMed]
  • Mackay TF. Quantitative trait loci in Drosophila. Nat Rev Genet. 2001 Jan;2(1):11–20. [PubMed]
  • Dobbs DA, Vanhessche KP, Brazi E, Rautenstrauch V, V, Lenoir JY, Genêt JP, Wiles J, Bergens SH. Industrial Synthesis of (+)-cis-Methyl Dihydrojasmonate by Enantioselective Catalytic Hydrogenation; Identification of the Precatalyst. Angew Chem Int Ed Engl. 2000 Jun 2;39(11):1992–1995. [PubMed]
  • Mackinnon MJ, Weller JI. Methodology and accuracy of estimation of quantitative trait loci parameters in a half-sib design using maximum likelihood. Genetics. 1995 Oct;141(2):755–770. [PMC free article] [PubMed]
  • Andersson L. Genetic dissection of phenotypic diversity in farm animals. Nat Rev Genet. 2001 Feb;2(2):130–138. [PubMed]
  • Meuwissen TH, Goddard ME. Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics. 2000 May;155(1):421–430. [PMC free article] [PubMed]
  • Charlier C, Farnir F, Berzi P, Vanmanshoven P, Brouwers B, Vromans H, Georges M. Identity-by-descent mapping of recessive traits in livestock: application to map the bovine syndactyly locus to chromosome 15. Genome Res. 1996 Jul;6(7):580–589. [PubMed]
  • Reich DE, Cargill M, Bolk S, Ireland J, Sabeti PC, Richter DJ, Lavery T, Kouyoumjian R, Farhadian SF, Ward R, et al. Linkage disequilibrium in the human genome. Nature. 2001 May 10;411(6834):199–204. [PubMed]
  • Churchill GA, Doerge RW. Empirical threshold values for quantitative trait mapping. Genetics. 1994 Nov;138(3):963–971. [PMC free article] [PubMed]
  • Riquet J, Coppieters W, Cambisano N, Arranz JJ, Berzi P, Davis SK, Grisart B, Farnir F, Karim L, Mni M, et al. Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9252–9257. [PMC free article] [PubMed]
  • Spelman RJ, van Arendonk JA. Effect of inaccurate parameter estimates on genetic response to marker-assisted selection in an outbred population. J Dairy Sci. 1997 Dec;80(12):3399–3410. [PubMed]
  • Coppieters W, Kvasz A, Farnir F, Arranz JJ, Grisart B, Mackinnon M, Georges M. A rank-based nonparametric method for mapping quantitative trait loci in outbred half-sib pedigrees: application to milk production in a granddaughter design. Genetics. 1998 Jul;149(3):1547–1555. [PMC free article] [PubMed]
  • Spelman RJ, Coppieters W, Karim L, van Arendonk JA, Bovenhuis H. Quantitative trait loci analysis for five milk production traits on chromosome six in the Dutch Holstein-Friesian population. Genetics. 1996 Dec;144(4):1799–1808. [PMC free article] [PubMed]
  • Spielman RS, McGinnis RE, Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed]
  • Darvasi A. Experimental strategies for the genetic dissection of complex traits in animal models. Nat Genet. 1998 Jan;18(1):19–24. [PubMed]
  • Dunner S, Charlier C, Farnir F, Brouwers B, Canon J, Georges M. Towards interbreed IBD fine mapping of the mh locus: double-muscling in the Asturiana de los Valles breed involves the same locus as in the Belgian Blue cattle breed. Mamm Genome. 1997 Jun;8(6):430–435. [PubMed]
  • Terwilliger JD, Weiss KM. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol. 1998 Dec;9(6):578–594. [PubMed]
  • Farnir F, Coppieters W, Arranz JJ, Berzi P, Cambisano N, Grisart B, Karim L, Marcq F, Moreau L, Mni M, et al. Extensive genome-wide linkage disequilibrium in cattle. Genome Res. 2000 Feb;10(2):220–227. [PubMed]
  • Thaller G, Hoeschele I. Fine-mapping of quantitative trait loci in half-sib families using current recombinations. Genet Res. 2000 Aug;76(1):87–104. [PubMed]
  • Flint J, Mott R. Finding the molecular basis of quantitative traits: successes and pitfalls. Nat Rev Genet. 2001 Jun;2(6):437–445. [PubMed]
  • VanRaden PM, Wiggans GR. Derivation, calculation, and use of national animal model information. J Dairy Sci. 1991 Aug;74(8):2737–2746. [PubMed]
  • Georges M, Nielsen D, Mackinnon M, Mishra A, Okimoto R, Pasquino AT, Sargeant LS, Sorensen A, Steele MR, Zhao X, et al. Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing. Genetics. 1995 Feb;139(2):907–920. [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...


  • Gene
    Gene links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...