EVIDENCE FOR AT LEAST 8 FANCONI-ANEMIA GENES

Fanconi anemia (FA) is an autosomal recessive chromosomal breakage dis order with diverse clinical symptoms including progressive bone marrow failure and increased cancer risk. FA cells are hypersensitive to cro sslinking agents, which has been exploited to assess genetic heterogen eity through complementation analysis. Five complementation groups (FA -A through FA-E) have so far been distinguished among the first 20 FA patients analyzed. Complementation groups in FA are likely to represen t distinct disease genes, two of which (FAG and EAA) have been cloned. Following the identification of the first FA-E patient, additional pa tients were identified whose cell lines complemented groups A-D. To as sess their possible assignment to the E group, we introduced selection markers into the original FA-E cell line and analyzed fusion hybrids with three cell lines classified as non-ABCD. All hybrids were complem ented for crosslinker sensitivity, indicating nonidentity with group E . We then marked the three non-ABCDE cell lines and examined all possi ble hybrid combinations for complementation, which indicated that each individual cell line represented a separate complementation group. Th ese results thus define three new groups, FA-F, FA-G, and FA-H, provid ing evidence for a minimum of eight distinct FA genes.