Estimation of distances and map construction using radiation hybrids.

A method of estimating distances between pairs of genetic markers is described that directly uses their observed joint frequency distribution in a panel of radiation hybrids (RHs). The distance measure is based on the strength of association between marker pairs, which is high for close markers and decays with distance. These distances are then submitted to a previous method that generates linear coordinates for the markers directly from the intermarker distance matrix. This method of map building from RH data is simpler than others, because it uses only the observed joint frequency distributions of markers in the panel, and does not attempt to model unobserved quantities such as the retention of different sized fragments that contain the markers. It also incorporates directly the observed variation in retention of different markers, without needing a model for differential fragment retention dependent on chromosomal location, which is generally not known. Only small, precise distances are used in map construction, thereby reducing any effects of different fragment retention frequencies and local variations in X-ray sensitivity. The method is tested by simulation, and known marker distances and locations are successfully recovered from RH raw data. The method is also applied to publicly available data sets related to the recent transcript map of the human genome.