Estimation of conditional multilocus gene identity among relatives

resolution of the genetic factors affecting complex traits. These include analysis with multipoint methods, use of extended pedigrees, and selective sampling of pedigrees. By sampling the affected individuals in an extended pedigree, we obtain individuals who have an increased probability of sharing genes identical by descent (IBD) at marker loci that are linked to the trait locus or loci. Given marker data on specified members of a pedigree, the conditional IBD status among relatives can be assessed, but exact computation is often impractical for multiple linked markers on complex pedigrees. The use of Markov chain Monte Carlo (MCMC) methods greatly extends the range of models and data sets for which analysis is computationally feasible. Many forms of MCMC have now been implemented in the context of genetic analysis. Here we propose a new sampler, which takes as latent variables the segregation indicators at marker loci, and jointly updates all indicators corresponding to a given meiosis. The sampler has good mixing properties. Questions of irreducibility are also addressed.

[1]  A. Sturtevant,et al.  THE LINEAR ARRANGEMENT OF SIX SEX-LINKED FACTORS IN DROSOPHILA, AS SHOWN BY THEIR MODE OF ASSOCIATION , 1913 .

[2]  Rory A. Fisher,et al.  The Systematic Location of Genes by Means of Crossover Observations , 1922, The American Naturalist.

[3]  Rory A. Fisher,et al.  THE AMOUNT OF INFORMATION SUPPLIED BY RECORDS OF FAMILIES AS A FUNCTION OF THE LINKAGE IN THE POPULATION SAMPLED , 1934 .

[4]  J. Haldane METHODS FOR THE DETECTION OF AUTOSOMAL LINKAGE IN MAN , 1934 .

[5]  R. Elston,et al.  A general model for the genetic analysis of pedigree data. , 1971, Human heredity.

[6]  E A Thompson,et al.  Gene identities and multiple relationships. , 1974, Biometrics.

[7]  Probability functions on complex pedigrees , 1978 .

[8]  E S Lander,et al.  Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. , 1987, Science.

[9]  M. Boehnke,et al.  Estimating the power of a proposed linkage study for a complex genetic trait. , 1989, American journal of human genetics.

[10]  K Lange,et al.  Simulation of pedigree genotypes by random walks. , 1989, American journal of human genetics.

[11]  N. Sheehan,et al.  Image processing procedures applied to the estimation of genotypes , 1989 .

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

[13]  E Sobel,et al.  Metropolis sampling in pedigree analysis , 1993, Statistical methods in medical research.

[14]  S Lin,et al.  An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees , 1994, Annals of human genetics.

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

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

[17]  C. Geyer,et al.  Annealing Markov chain Monte Carlo with applications to ancestral inference , 1995 .

[18]  E M Wijsman,et al.  Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers. , 1996, American journal of human genetics.

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

[20]  S Lin,et al.  Incorporating crossover interference into pedigree analysis using the chi 2 model. , 1996, Human heredity.

[21]  E. Wijsman,et al.  Genetic analysis of simulated oligogenic traits in nuclear and extended pedigrees: Summary of GAW10 contributions , 1997, Genetic epidemiology.

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

[23]  S. Heath Generating Consistent Genotypic Configurations for Multi-Allelic Loci and Large Complex Pedigrees , 1998, Human Heredity.