A Program Using Loss-of-Constitutional-Heterozygosity Data to Ascertain the Location of Predisposing Genes in Cancer Families

Abstract

We present a modification of the MLINK program, which enables the formal incorporation of data on loss of constitutional heterozygosity (LOCH) into likelihood calculations. This is an implementation of a previously described approach to localise tumour suppressor genes involved in 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 method facilitates the use of small families, in particular parent-offspring pairs, which would otherwise be uninformative. The technique also has an advantage in view of the increasing use of archival material, which is often derived from specimens taken for histopathological analysis, and may contain tumour tissue which can also be used to obtain additional information. We describe the use of the program, the interpretation of the results and the advantages and limitations of this approach.