Bayesian mapping of multiple quantitative trait loci from incomplete outbred offspring data.

A general fine-scale Bayesian quantitative trait locus (QTL) mapping method for outcrossing species is presented. It is suitable for an analysis of complete and incomplete data from experimental designs of F2 families or backcrosses. The amount of genotyping of parents and grandparents is optional, as well as the assumption that the QTL alleles in the crossed lines are fixed. Grandparental origin indicators are used, but without forgetting the original genotype or allelic origin information. The method treats the number of QTL in the analyzed chromosome as a random variable and allows some QTL effects from other chromosomes to be taken into account in a composite interval mapping manner. A block-update of ordered genotypes (haplotypes) of the whole family is sampled once in each marker locus during every round of the Markov Chain Monte Carlo algorithm used in the numerical estimation. As a byproduct, the method gives the posterior distributions for linkage phases in the family and therefore it can also be used as a haplotyping algorithm. The Bayesian method is tested and compared with two frequentist methods using simulated data sets, considering two different parental crosses and three different levels of available parental information. The method is implemented as a software package and is freely available under the name Multimapper/outbred at URL http://www.rni.helsinki.fi/mjs/.

[1]  P. Green,et al.  On Bayesian Analysis of Mixtures with an Unknown Number of Components (with discussion) , 1997 .

[2]  S. Heath Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. , 1997, American journal of human genetics.

[3]  J. Satagopan Estimating the number of quantitative trait loci via Bayesian model determination , 1996 .

[4]  C. Haley,et al.  Mapping quantitative trait loci in crosses between outbred lines using least squares. , 1994, Genetics.

[5]  I. Hoeschele,et al.  Advances in statistical methods to map quantitative trait loci in outbred populations. , 1997, Genetics.

[6]  Z B Zeng,et al.  Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Jansen,et al.  Interval mapping of multiple quantitative trait loci. , 1993, Genetics.

[8]  N. Sheehan,et al.  Problems with determination of noncommunicating classes for Monte Carlo Markov chain applications in pedigree analysis. , 1998, Biometrics.

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

[10]  Z. Zeng Precision mapping of quantitative trait loci. , 1994, Genetics.

[11]  S Lin,et al.  Finding noncommunicating sets for Markov chain Monte Carlo estimations on pedigrees. , 1994, American journal of human genetics.

[12]  P. Green,et al.  Corrigendum: On Bayesian analysis of mixtures with an unknown number of components , 1997 .

[13]  C. Kao,et al.  General formulas for obtaining the MLEs and the asymptotic variance-covariance matrix in mapping quantitative trait loci when using the EM algorithm. , 1997, Biometrics.

[14]  D. Neale,et al.  Multiple marker mapping of quantitative trait loci in an outbred pedigree of loblolly pine , 1997, Theoretical and Applied Genetics.

[15]  M A Newton,et al.  A bayesian approach to detect quantitative trait loci using Markov chain Monte Carlo. , 1996, Genetics.

[16]  I. Hoeschele,et al.  Mapping-linked quantitative trait loci using Bayesian analysis and Markov chain Monte Carlo algorithms. , 1997, Genetics.

[17]  P. Green Reversible jump Markov chain Monte Carlo computation and Bayesian model determination , 1995 .

[18]  E. Wijsman A deductive method of haplotype analysis in pedigrees. , 1987, American journal of human genetics.

[19]  M. Daly,et al.  Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. , 1995, American journal of human genetics.

[20]  C S Jensen,et al.  Blocking Gibbs sampling for linkage analysis in large pedigrees with many loops. , 1999, American journal of human genetics.

[21]  R. Jansen,et al.  A mixture model approach to the mapping of quantitative trait loci in complex populations with an application to multiple cattle families. , 1998, Genetics.

[22]  S Lin A scheme for constructing an irreducible Markov chain for pedigree data. , 1995, Biometrics.

[23]  Leonid Kruglyak,et al.  The use of a genetic map of biallelic markers in linkage studies , 1997, Nature Genetics.

[24]  R. Jansen,et al.  University of Groningen High Resolution of Quantitative Traits Into Multiple Loci via Interval Mapping , 2022 .

[25]  N. Sheehan,et al.  On the irreducibility of a Markov chain defined on a space of genotype configurations by a sampling scheme. , 1993, Biometrics.

[26]  E. Thompson Monte Carlo Likelihood in Genetic Mapping , 1994 .

[27]  E. Lander,et al.  Construction of multilocus genetic linkage maps in humans. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Jansen A general Monte Carlo method for mapping multiple quantitative trait loci. , 1996, Genetics.

[29]  K Lange,et al.  Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. , 1996, American journal of human genetics.