Point and interval estimates of marker location in radiation hybrid mapping.
Radiation hybrid (RH) mapping is a powerful method for ordering loci on chromosomes and for estimating the distances between them. RH mapping is currently used to construct both framework maps, in which all markers are ordered with high confidence (e.g., 1,000:1 relative maximum likelihood), and comprehensive maps, which include markers with less-confident placement. To deal with uncertainty in the order and location of markers, marker positions may be estimated conditional on the most likely marker order, plausible intervals for nonframework markers may be indicated on a framework map, or bins of markers may be constructed. We propose a statistical method for estimating marker position that combines information from all plausible marker orders, gives a measure of uncertainty in location for each marker, and provides an alternative to the current practice of binning. Assuming that the prior distribution for the retention probabilities is uniform and that the marker loci are distributed independently and uniformly on an interval of specified length, we calculate the posterior distribution of marker position for each marker. The median or mean of this distribution provides a point estimate of marker location. An interval estimate of marker location may be constructed either by using the 100(alpha/2) and 100(1-alpha)/2 percentiles of the distribution to form a 100(1-alpha) % posterior credible interval or by calculating the shortest 100(1-alpha) % posterior credible interval. These point and interval estimates take into account ordering uncertainty and do not depend on the assumption of a particular marker order. We evaluate the performance of the estimates on the basis of results from simulated data and illustrate the method with two examples.
Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, USA.
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Stringham
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Boehnke
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Lange
D001499:Bayes Theorem; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003198:Computer Simulation; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D016013:Likelihood Functions; D008126:Lod Score; D020161:Physical Chromosome Mapping / Q000379:methods*; D016324:Sequence Tagged Sites; D016008:Statistical Distributions
D005819:Genetic Markers