ESTIMATING PHYSICAL DISTANCES FROM RADIATION HYBRID MAPPING DATA

Radiation hybrid mapping has become an established tool for building p hysical maps. It represents a powerful way of constructing YAC contigs and high-resolution maps for positional cloning experiments. Ideally, radiation hybrids should not only provide support for the true order of the markers, but also accurate estimates of the physical distances between them, Statistical analysis of radiation hybrids has proved dif ficult because of the number of parameters (representing the fragment retention probabilities) that must be estimated, and simplifying assum ptions are needed to analyze large numbers of markers simultaneously. The ramifications of these assumptions for the calculation of physical distances are investigated. A simple two-locus model is presented to demonstrate that variation in marker retention can lead to distortions in the estimates of distance. Multilocus simulations show that, when marker retention is constant. across the chromosome, good estimates of physical distance can be derived using simple models of retention. Ho wever, further simulations exploring variable retention schemes demons trate that significant errors in the estimates of map distances can oc cur. Ways of minimizing these distortions are discussed. (C) 1997 Acad emic Press.