title: Evidence for at least eight Fanconi anemia genes.
abstract: Fanconi anemia (FA) is an autosomal recessive chromosomal breakage disorder with diverse clinical symptoms including progressive bone marrow failure and increased cancer risk. FA cells are hypersensitive to crosslinking agents, which has been exploited to assess genetic heterogeneity 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 represent distinct disease genes, two of which (FAC and FAA) have been cloned. Following the identification of the first FA-E patient, additional patients were identified whose cell lines complemented groups A-D. To assess 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 complemented for cross-linker sensitivity, indicating nonidentity with group E. We then marked the three non-ABCDE cell lines and examined all possible hybrid combinations for complementation, which indicated that each individual cell line represented a separate complementation group. These results thus define three new groups, FA-F, FA-G, and FA-H, providing evidence for a minimum of eight distinct FA genes.
authors.affiliation: Department of Human Genetics, Free University, Amsterdam, The Netherlands. H.Joenje.HumGen@med.vu.nl
authors.forename: H
authors.initials: H
authors.lastname: Joenje
authors.forename: A B
authors.initials: AB
authors.lastname: Oostra
authors.forename: M
authors.initials: M
authors.lastname: Wijker
authors.forename: F M
authors.initials: FM
authors.lastname: di Summa
authors.forename: C G
authors.initials: CG
authors.lastname: van Berkel
authors.forename: M A
authors.initials: MA
authors.lastname: Rooimans
authors.forename: W
authors.initials: W
authors.lastname: Ebell
authors.forename: M
authors.initials: M
authors.lastname: van Weel
authors.forename: J C
authors.initials: JC
authors.lastname: Pronk
authors.forename: M
authors.initials: M
authors.lastname: Buchwald
authors.forename: F
authors.initials: F
authors.lastname: Arwert
mesh_terms: D019677:Artificial Gene Fusion; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D004198:Disease Susceptibility; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics*; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats; D018598:Minisatellite Repeats; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D014162:Transfection
chemical_list: D005819:Genetic Markers