Nature Genetics
14, 324 - 328 (1996)
doi:10.1038/ng1196-324
Positional cloning of the Fanconi anaemia group A geneSinoula Apostolou*1,13, Scott A. Whitmore*1,13, Joanna Crawford1,13, Gregory Lennon2,13, Grant R. Sutherland1,13, David F. Callen1,13, Leonarda lanzano3,14, Maria Savino3,14, Maria D'Apolito3,14, Angelo Notarangeio3,14, Elena Memeo3,14, Maria Rosaria Piemontese3,14, Leopoldo Zelante3,14, Anna Savoia3,12,14, Rachel A. Gibson4,15, Alex J. Tipping4,15, Neil V. Morgan4,15, Sheila Hassock4,15, Stander Jansen5,15, Thomy J. de Ravel6,15, Carola Van Berkell7,15, Jan C. Pronk7,15, Douglas F. Easton8,15, Christopher G. Mathew4,12,15, Orna Levran9,16, Peter C. Verlander9,16, Sat Dev Batish9,16, Tamar Erlich9,16, Arleen D. Auerbach9,12,16, Anne-Marie Cleton-Jansen10,17, Elna W. Moerland10,17, Cees J. Cornelisse10,17, Norman A. Doggett11,18, Larry L. Deaven11,18
& Robert K. Moyzis11,18
1Dept of Cytogenetics and Molecular Genetics, Adelaide Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia
2Human Genome Centre, L-452 Lawrence Livermore National Laboratory, Livermore, California 94550, USA
3Ospedale Casa Sollievo della Sofferenza, 1-71013 San Giovanni Rotondo, Foggia, Italy
4Division of Medical & Molecular Genetics UMDS, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK
5Dept of Human Genetics, Univ of the Orange Free State, South Africa
6Dept of Human Genetics, South African Institute of Medical Research & Univ of the Witwatersrand, South Africa
7Dept of Human Genetics, Free Univ, Amsterdam, The Netherlands
8Genetic Epidemiology Unit, Institute of Public Health, Univ of Cambridge, UK
9Laboratory of Human Genetics and Hematology, The Rockefeller Univ, 1230 York Avenue, New York, New York 10021-6399, USA
10Dept of Pathology, Univ of Leiden, The Netherlands
11Center for Human Genome Studies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
12Correspondence should be addressed to C.G.M., A.S. or A.D.A.
13The Fanconi anaemia/Breast cancer consortium: Group 1
14The Fanconi anaemia/Breast cancer consortium: Group 2
15The Fanconi anaemia/Breast cancer consortium: Group 3
16The Fanconi anaemia/Breast cancer consortium: Group 4
17The Fanconi anaemia/Breast cancer consortium: Group 5
18The Fanconi anaemia/Breast cancer consortium: Group 6
*S.A. and S.A.W. contributed equally The Fanconi anaemia/Breast cancer consortium*
Fanconi anaemia (FA) is an autosomal recessive disorder associated with progressive bone-marrow failure, a variety of congenital abnormalities, and predisposition to acute myeloid leukaemia1. Cells from FA patients show increased sensitivity to bifunctional DNA crosslinking agents such as diepoxybutane and mitomycin C, with characteristic chromosome breakage2. FA is genetically heterogeneous, at least five different complementation groups (FA-A to FA-E) having been described3,4. The gene for group C (FAC) was cloned by functional complementation and mapped to chromosome 9q22.3 (refs 3, 5), but the genes for the other complementation groups have not yet been identified. The group A gene (FAA) has recently been mapped to chromosome 16q24.3 by linkage analysis6, and accounts for 60−65% of FA cases7,8. We narrowed the candidate region by linkage and allelic association analysis, and have isolated a gene that is mutated in FA-A patients. The gene encodes a protein of 1,455 amino acids that has no significant homology to any other known proteins, and may therefore represent a new class of genes associated with the prevention or repair of DNA damage.
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