Fanconi anaemia (FA) is an autosomal recessive disorder characterized by progressive pancytopenia, short stature, radial ray defects, skin hyper-pigmentation and a predisposition to cancer1,2. Cells from FA patients are hypersensitive to cell killing and chromosome breakage induced by DNA cross-linking agents such as mitomycin C (MMC) and diepoxybutane (DEB)3,4. Consequently, the defect in FA is thought to be in DNA crosslink repair. Additional cellular phenotypes of FA include oxygen sensitivity5,6, poor cell growth7 and a G2 cell cycle delay8,9. At least 5 complementation groups for Fanconi anaemia exist, termed A through E10,11. One of the five FA genes, FA(C), has been identified by cDNA complementation12, but no other FA genes have been mapped or cloned until now. The strategy of cDNA complementation, which was successful for identifying the FA(C) gene has not yet been successful for cloning additional FA genes. The alternative approach of linkage analysis, followed by positional cloning, is hindered in FA by genetic heterogeneity and the lack of a simple assay for determining complementation groups. In contrast to genetic linkage studies, microcell mediated chromosome transfer utilizes functional complementation to identify the disease bearing chromosome13. Here we report the successful use of this technique to map the gene for the rare FA complementation group D (FA(D)).
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