Point and interval estimates of marker location in radiation hybrid mapping

Citation
Hm. Stringham et al., Point and interval estimates of marker location in radiation hybrid mapping, AM J HU GEN, 65(2), 1999, pp. 545-553
Citations number
11
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Journal title
AMERICAN JOURNAL OF HUMAN GENETICS
ISSN journal
00029297 → ACNP
Volume
65
Issue
2
Year of publication
1999
Pages
545 - 553
Database
ISI
SICI code
0002-9297(199908)65:2<545:PAIEOM>2.0.ZU;2-Q
Abstract
Radiation hybrid (RH) mapping is a powerful method for ordering loci on chr omosomes and for estimating the distances between them. RH mapping is curre ntly used to construct both framework maps, in which all markers are ordere d with high confidence (e.g., 1,000:1 relative maximum likelihood), and com prehensive maps, which include markers with less-confident placement. To de al with uncertainty in the order and location of markers, marker positions may be estimated conditional on the. most likely marker order, plausible in tervals for nonframework markers may be indicated on a framework map, or bi ns of markers may be constructed. We propose a statistical method for estim ating marker position that combines information from all plausible marker o rders, gives a measure of uncertainty in location for each marker, and prov ides an alternative to the current practice of binning. Assuming that the p rior distribution for the retention probabilities is uniform and that the m arker loci are distributed independently and uniformly on an interval of sp ecified length, we calculate the posterior distribution of marker position for each marker. The median or mean of this distribution provides a point e stimate of marker location. An interval estimate of marker location may be constructed either by using the 100(alpha/2) and 100(1 - alpha)/2 percentil es of the distribution to form a 100(1 - alpha)% posterior credible interva l or by calculating the shortest 100(1 - alpha)% posterior credible interva l. These point and interval estimates take into account ordering uncertaint y and do not depend on the assumption of a particular marker order. We eval uate the performance of the estimates on the basis of results from simulate d data and illustrate the method with two examples.