Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data

A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD) information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC) methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

[1]  Z B Zeng,et al.  Joint linkage and linkage disequilibrium mapping in natural populations. , 2001, Genetics.

[2]  M. Goddard,et al.  The distribution of the effects of genes affecting quantitative traits in livestock , 2001, Genetics Selection Evolution.

[3]  M. Sillanpää,et al.  Bayesian Association Mapping for Quantitative Traits in a Mixture of Two Populations , 2001, Genetic epidemiology.

[4]  M. Sillanpää,et al.  Bayesian oligogenic analysis of quantitative and qualitative traits in general pedigrees , 2001, Genetic epidemiology.

[5]  Karl W. Broman,et al.  A model selection approach for the identification of quantitative trait loci in experimental crosses , 2002 .

[6]  Sylvia Richardson,et al.  Stochastic search variable selection , 1995 .

[7]  M. Mni,et al.  Extensive genome-wide linkage disequilibrium in cattle. , 2000, Genome research.

[8]  M. Mni,et al.  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. , 2002, Genetics.

[9]  M. Sillanpää,et al.  Multiple QTL mapping in related plant populations via a pedigree-analysis approach , 2002, Theoretical and Applied Genetics.

[10]  M S McPeek,et al.  Estimation of variance components of quantitative traits in inbred populations. , 2000, American journal of human genetics.

[11]  Michel Georges,et al.  Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. , 2002, Nature Reviews Genetics.

[12]  M. Goddard The validity of genetic models underlying quantitative traits , 2001 .

[13]  Peter Beighton,et al.  de la Chapelle, A. , 1997 .

[14]  M. Sillanpää,et al.  Model choice in gene mapping: what and why. , 2002, Trends in genetics : TIG.

[15]  B. Guldbrandtsen,et al.  Multitrait fine mapping of quantitative trait loci using combined linkage disequilibria and linkage analysis. , 2003, Genetics.

[16]  Sigbjørn Lien,et al.  Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping. , 2002, Genetics.

[17]  M. Goddard,et al.  Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. , 2000, Genetics.

[18]  M. Goddard,et al.  Prediction of identity by descent probabilities from marker-haplotypes , 2001, Genetics Selection Evolution.

[19]  G. Churchill,et al.  A statistical framework for quantitative trait mapping. , 2001, Genetics.

[20]  M Grossman,et al.  Marker assisted selection using best linear unbiased prediction , 1989, Genetics Selection Evolution.

[21]  M. Sillanpää,et al.  Bayesian mapping of multiple quantitative trait loci from incomplete inbred line cross data. , 1998, Genetics.

[22]  Eric Lander,et al.  Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland , 1992, Nature Genetics.

[23]  R. Ball,et al.  Bayesian methods for quantitative trait loci mapping based on model selection: approximate analysis using the Bayesian information criterion. , 2001, Genetics.

[24]  H. Akaike,et al.  Information Theory and an Extension of the Maximum Likelihood Principle , 1973 .

[25]  Miguel Pérez-Enciso,et al.  Fine mapping of complex trait genes combining pedigree and linkage disequilibrium information: a Bayesian unified framework. , 2003, Genetics.

[26]  P. VanRaden,et al.  Application of a canonical transformation to detection of quantitative trait loci with the aid of genetic markers in a multi-trait experiment , 1996, Theoretical and Applied Genetics.

[27]  I. D. Boer,et al.  Genetic evaluation methods for populations with dominance and inbreeding , 1993, Theoretical and Applied Genetics.

[28]  G. Casella,et al.  Joint linkage and linkage disequilibrium mapping of quantitative trait loci in natural populations. , 2002, Genetics.

[29]  R. N. Curnow,et al.  Estimating the locations and the sizes of the effects of quantitative trait loci using flanking markers , 1992, Theoretical and Applied Genetics.