Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping

T.H.E. Meuwissen, A. Karlsen, S. Lien, I. Olsaker, M.E. Goddard

    Research output: Contribution to journalArticleAcademicpeer-review

    211 Citations (Scopus)

    Abstract

    A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.
    Original languageEnglish
    Pages (from-to)373-379
    JournalGenetics
    Volume161
    Publication statusPublished - 2002

    Fingerprint

    Chromosome Mapping
    Quantitative Trait Loci
    Linkage Disequilibrium
    Chromosomes, Human, Pair 5
    Haplotypes
    Genetic Recombination
    Pedigree
    Genes
    Chromosomes
    Alleles
    Mutation

    Cite this

    Meuwissen, T. H. E., Karlsen, A., Lien, S., Olsaker, I., & Goddard, M. E. (2002). Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping. Genetics, 161, 373-379.
    Meuwissen, T.H.E. ; Karlsen, A. ; Lien, S. ; Olsaker, I. ; Goddard, M.E. / Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping. In: Genetics. 2002 ; Vol. 161. pp. 373-379.
    @article{e9fee94b415846a6be83276022d24cc2,
    title = "Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping",
    abstract = "A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.",
    author = "T.H.E. Meuwissen and A. Karlsen and S. Lien and I. Olsaker and M.E. Goddard",
    year = "2002",
    language = "English",
    volume = "161",
    pages = "373--379",
    journal = "Genetics",
    issn = "0016-6731",
    publisher = "Genetics Society of America",

    }

    Meuwissen, THE, Karlsen, A, Lien, S, Olsaker, I & Goddard, ME 2002, 'Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping', Genetics, vol. 161, pp. 373-379.

    Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping. / Meuwissen, T.H.E.; Karlsen, A.; Lien, S.; Olsaker, I.; Goddard, M.E.

    In: Genetics, Vol. 161, 2002, p. 373-379.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping

    AU - Meuwissen, T.H.E.

    AU - Karlsen, A.

    AU - Lien, S.

    AU - Olsaker, I.

    AU - Goddard, M.E.

    PY - 2002

    Y1 - 2002

    N2 - A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.

    AB - A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.

    M3 - Article

    VL - 161

    SP - 373

    EP - 379

    JO - Genetics

    JF - Genetics

    SN - 0016-6731

    ER -