Fine-scale mapping of disease loci via shattered coalescent modeling of genealogies. Export

@article{citeulike:2076757, abstract = {We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. The method explicitly models the genealogy underlying a sample of case chromosomes in the vicinity of a putative disease locus, in contrast with the assumption of a star-shaped tree made by many existing multipoint methods. Within this modeling framework, we can allow for missing marker information and for uncertainty about the true underlying genealogy and the makeup of ancestral marker haplotypes. A crucial advantage of our method is the incorporation of the shattered coalescent model for genealogies, allowing for multiple founding mutations at the disease locus and for sporadic cases of disease. Output from the method includes approximate posterior distributions of the location of the disease locus and population-marker haplotype proportions. In addition, output from the algorithm is used to construct a cladogram to represent genetic heterogeneity at the disease locus, highlighting clusters of case chromosomes sharing the same mutation. We present detailed simulations to provide evidence of improvements over existing methodology. Furthermore, inferences about the location of the disease locus are shown to remain robust to modeling assumptions.}, address = {Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. amorris@well.ox.ac.uk}, author = {Morris, A. P. and Whittaker, J. C. and Balding, D. J.}, citeulike-article-id = {2076757}, citeulike-linkout-0 = {http://dx.doi.org/10.1086/339271}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11836651}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11836651}, doi = {10.1086/339271}, issn = {0002-9297}, journal = {American journal of human genetics}, keywords = {association, genealogy, ldmapping}, month = {March}, number = {3}, pages = {686--707}, posted-at = {2009-01-18 14:51:35}, priority = {0}, title = {Fine-scale mapping of disease loci via shattered coalescent modeling of genealogies.}, url = {http://dx.doi.org/10.1086/339271}, volume = {70}, year = {2002} }

TY - JOUR ID - citeulike:2076757 L3 - citeulike-article-id:2076757 N2 - We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. The method explicitly models the genealogy underlying a sample of case chromosomes in the vicinity of a putative disease locus, in contrast with the assumption of a star-shaped tree made by many existing multipoint methods. Within this modeling framework, we can allow for missing marker information and for uncertainty about the true underlying genealogy and the makeup of ancestral marker haplotypes. A crucial advantage of our method is the incorporation of the shattered coalescent model for genealogies, allowing for multiple founding mutations at the disease locus and for sporadic cases of disease. Output from the method includes approximate posterior distributions of the location of the disease locus and population-marker haplotype proportions. In addition, output from the algorithm is used to construct a cladogram to represent genetic heterogeneity at the disease locus, highlighting clusters of case chromosomes sharing the same mutation. We present detailed simulations to provide evidence of improvements over existing methodology. Furthermore, inferences about the location of the disease locus are shown to remain robust to modeling assumptions. IS - 3 JF - American journal of human genetics SN - 0002-9297 AD - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. amorris@well.ox.ac.uk EP - 707 TI - Fine-scale mapping of disease loci via shattered coalescent modeling of genealogies. VL - 70 SP - 686 KW - association KW - genealogy KW - ldmapping AU - Morris, AP AU - Whittaker, JC AU - Balding, DJ PY - 2002/03// UR - http://dx.doi.org/10.1086/339271 ER -