A PROGRAM USING LOSS-OF-CONSTITUTIONAL-HETEROZYGOSITY DATA TO ASCERTAIN THE LOCATION OF PREDISPOSING GENES IN CANCER FAMILIES

We present a modification of the MLINK program, which enables the form al incorporation of data on loss of constitutional heterozygosity (LOC H) into likelihood calculations. This is an implementation of a previo usly described approach to localise tumour suppressor genes involved i n inherited cancer predisposition. LOCH data are treated as additional observations on disease phenotype. The main effect of including extra data is to enhanace the power to detect linkage. In this way, the met hod facilitates the use of small families, in particular parent-offspr ing pairs, which would otherwise be uninformative. The technique also has an advantage in view of the increasing use of archival material, w hich is often derived from specimens taken for histopathological analy sis, and may contain tumour tissue which can also be used to obtain ad ditional information. We describe the use of the program, the interpre tation of the results and the advantages and limitations of this appro ach.