GENETIC-MAPPING OF THE FACC GENE AND LINKAGE ANALYSIS IN FANCONI-ANEMIA FAMILIES

Fanconi anaemia is an autosomal recessive disorder associated with inc reased chromosome breakage and progressive bone marrow failure. The ge ne for complementation group C (FACC) has been cloned and mapped to ch romosome 9q22.3, but neither its genetic location nor the proportion o f patients belonging to group C is known. We have used a polymorphism within the FACC gene to localise it within a 5 cM interval on chromoso me 9q, bounded by D9S196/D9S197 and D9S176. The genes for Gorlin's syn drome and multiple self-healing squamous epitheliomata have also been mapped to this interval. Linkage analysis with the three highly inform ative microsatellite polymorphisms flanking FACC in 36 Fanconi anaemia families showed that only 8% of families were linked to this locus. T his indicates that the genes for the other fanconi anaemia complementa tion groups must map to one or more different chromosomal locations. T he markers also allowed rapid exclusion of 56% of the families in our panel from complementation group C, thus substantially reducing the nu mber of patients who need to be screened for FACC mutations.