• 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. Mar 2002; 160(3): 1113–1122.
PMCID: PMC1462013

Linkage disequilibrium in domestic sheep.

Abstract

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.

Full Text

The Full Text of this article is available as a PDF (206K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hedrick PW. Gametic disequilibrium measures: proceed with caution. Genetics. 1987 Oct;117(2):331–341. [PMC free article] [PubMed]
  • Jorde LB. Linkage disequilibrium and the search for complex disease genes. Genome Res. 2000 Oct;10(10):1435–1444. [PubMed]
  • Kambadur R, Sharma M, Smith TP, Bass JJ. Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle. Genome Res. 1997 Sep;7(9):910–916. [PubMed]
  • Kruglyak L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet. 1999 Jun;22(2):139–144. [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]
  • Lewontin RC. On measures of gametic disequilibrium. Genetics. 1988 Nov;120(3):849–852. [PMC free article] [PubMed]
  • Abecasis GR, Cookson WO. GOLD--graphical overview of linkage disequilibrium. Bioinformatics. 2000 Feb;16(2):182–183. [PubMed]
  • Maddox JF, Davies KP, Crawford AM, Hulme DJ, Vaiman D, Cribiu EP, Freking BA, Beh KJ, Cockett NE, Kang N, et al. An enhanced linkage map of the sheep genome comprising more than 1000 loci. Genome Res. 2001 Jul;11(7):1275–1289. [PMC free article] [PubMed]
  • Abecasis GR, Noguchi E, Heinzmann A, Traherne JA, Bhattacharyya S, Leaves NI, Anderson GG, Zhang Y, Lench NJ, Carey A, et al. Extent and distribution of linkage disequilibrium in three genomic regions. Am J Hum Genet. 2001 Jan;68(1):191–197. [PMC free article] [PubMed]
  • Milan D, Jeon JT, Looft C, Amarger V, Robic A, Thelander M, Rogel-Gaillard C, Paul S, Iannuccelli N, Rask L, et al. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science. 2000 May 19;288(5469):1248–1251. [PubMed]
  • Andersson L, Haley CS, Ellegren H, Knott SA, Johansson M, Andersson K, Andersson-Eklund L, Edfors-Lilja I, Fredholm M, Hansson I, et al. Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science. 1994 Mar 25;263(5154):1771–1774. [PubMed]
  • Montgomery GW, Crawford AM, Penty JM, Dodds KG, Ede AJ, Henry HM, Pierson CA, Lord EA, Galloway SM, Schmack AE, et al. The ovine Booroola fecundity gene (FecB) is linked to markers from a region of human chromosome 4q. Nat Genet. 1993 Aug;4(4):410–414. [PubMed]
  • Raadsma HW, McEwan JC, Stear MJ, Crawford AM. Genetic characterisation of protective vaccine responses in sheep using multi-valent Dichelobacter nodosus vaccines. Vet Immunol Immunopathol. 1999 Dec 15;72(1-2):219–229. [PubMed]
  • de Gortari MJ, Freking BA, Cuthbertson RP, Kappes SM, Keele JW, Stone RT, Leymaster KA, Dodds KG, Crawford AM, Beattie CW. A second-generation linkage map of the sheep genome. Mamm Genome. 1998 Mar;9(3):204–209. [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]
  • Dunning AM, Durocher F, Healey CS, Teare MD, McBride SE, Carlomagno F, Xu CF, Dawson E, Rhodes S, Ueda S, et al. The extent of linkage disequilibrium in four populations with distinct demographic histories. Am J Hum Genet. 2000 Dec;67(6):1544–1554. [PMC free article] [PubMed]
  • Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001 Feb 15;409(6822):928–933. [PubMed]
  • Eaves IA, Merriman TR, Barber RA, Nutland S, Tuomilehto-Wolf E, Tuomilehto J, Cucca F, Todd JA. The genetically isolated populations of Finland and sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Nat Genet. 2000 Jul;25(3):320–323. [PubMed]
  • Slatkin M. Linkage disequilibrium in growing and stable populations. Genetics. 1994 May;137(1):331–336. [PMC free article] [PubMed]
  • Eyre-Walker A. Do mitochondria recombine in humans? Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1573–1580. [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]
  • 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]
  • Terwilliger JD, Weiss KM. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol. 1998 Dec;9(6):578–594. [PubMed]
  • Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet. 2000 Jul;25(3):279–283. [PubMed]
  • Wilson JF, Goldstein DB. Consistent long-range linkage disequilibrium generated by admixture in a Bantu-Semitic hybrid population. Am J Hum Genet. 2000 Oct;67(4):926–935. [PMC free article] [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]
  • Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC, O'Connell AR, et al. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod. 2001 Apr;64(4):1225–1235. [PubMed]
  • Zapata C. The D' measure of overall gametic disequilibrium between pairs of multiallelic loci. Evolution. 2000 Oct;54(5):1809–1812. [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

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

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...