ALLELIC ASSOCIATION UNDER MAP ERROR AND RECOMBINATIONAL HETEROGENEITY- A TALE OF 2 SITES

Recombination acts on the genetic map, not on the physical map. On the other hand, the physical map is usually more accurate. Choice of the genetic or physical map for positional cloning by allelic association depends on the goodness of fit of data to each map under an establishe d model. Huntington disease illustrates the usual case in which the gr eater reliability of physical data outweighs recombinational heterogen eity. Hemochromatosis represents an er;exceptional case in which unrec ognized recombinational heterogeneity retarded positional cloning for a decade. The Malecot model performs well for major genes, but no appr oach assuming either equilibrium or disequilibrium has been validated for oligogenes contributing to common disease. In this case of greates t interest, the power of allelic association relative to linkage is le ss clear than for major genes.