Genetics, Vol. 161, 373-379, May 2002, Copyright © 2002

Fine Mapping of a Quantitative Trait Locus for Twinning Rate Using Combined Linkage and Linkage Disequilibrium Mapping

Theo H. E. Meuwissena, Astrid Karlsenb, Sigbjørn Lienb, Ingrid Olsakerc, and Mike E. Goddardd
a Institute for Animal Science and Health, Lelystad, 8200 AB The Netherlands,
b Agricultural University of Norway, Ås, 1432, Norway,
c Department of Morphology, Genetics and Aquatic Biology, Norwegian School of Veterinary Science, 0033 Oslo, Norway,
d Institute of Land and Food Resources, University of Melbourne, Parkville, 3052 Australia and Victorian Institute of Animal Science, Attwood, Victoria, 3049 Australia

Corresponding author: Theo H. E. Meuwissen, Box 65, Lelystad, 8200 AB The Netherlands., t.h.e.meuwissen{at}id.dlo.nl (E-mail)

Communicating editor: C. HALEY

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.




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