ESTIMATION OF DISTANCES AND MAP CONSTRUCTION USING RADIATION HYBRIDS

A method of estimating distances between pairs of genetic markers is d escribed that directly uses their observed joint Frequency distributio n in a panel of radiation hybrids (RHs). The distance measure is based on the strength of association between marker pairs, which is high fo r close markers and decays with distance. These distances are then sub mitted 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, a nd does not attempt to model unobserved quantities such as the retenti on of different sized fragments that contain the markers. It also inco rporates directly the observed variation in retention of different mar kers, without needing a model for differential fragment retention depe ndent on chromosomal location, which is generally not known. Only smal l, precise distances are used in map construction, thereby reducing an y effects of different fragment retention Frequencies and local variat ions in X-ray sensitivity. The method is tested by simulation, and kno wn marker distances and locations are successfully recovered from RH r aw data. The method is also applied to publicly available data sets re lated to the recent transcript map of the human genome.