Nature Genetics
11, 338 - 340 (1995)
doi:10.1038/ng1195-338
Localisation of the Fanconi anaemia complementation group A gene to chromosome 16q24.3Jan C. Pronk1, *, Rachel A. Gibson2, *, Anna Savoia3, *, Mario Wijker1, Neil V. Morgan2, Salvatore Melchionda3, Deborah Ford4, Samia Temtamy5, Juan J. Ortega6, Stander Jansen7, Charmaine Havenga7, Richard J. Cohn8, Thomy J. de Ravel8, Irene Roberts9, Andries Westerveld10, Douglas F. Easton4, Hans Joenje1, Christopher G. Mathew2
& Fré Arwert1
1Department of Human Genetics, Free University, Amsterdam, The Netherlands
2Division of Medical and Molecular Genetics UMDS, Guy's Hospital, London, UK
3Servizio di Genetica Medica, I.R.C.C.S.-Ospedale C.S.S., S. Giovanni Rotondo, Foggia, Italy
4Section of Epidemiology, Institute of Cancer Research, Surrey, UK
5Department of Human Genetics, National Research Centre, Cairo, Egypt
6Hematology and BMT Unit, Hospital Infantil Vall d'Hebron, Barcelona, Spain
7Departments of Human Genetics and Paediatrics, University of the Orange Free State Medical School, Bloemfontein, South Africa
8Departments of Human Genetics and Paediatrics, South African Institute of Medical Research and the University of the Witwatersrand, South Africa
9Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
10Department of Human Genetics, Academic Medical Centre, University of Amsterdam, The Netherlands
*The first three authors contributed equally to this study Correspondence should be addressed to J.C.P. Fanconi anaemia (FA) is an autosomal recessive disorder associated with diverse developmental abnormalities, bone-marrow failure and predisposition to cancer1. FA cells show increased chromosome breakage and hypersensitivity to DMA cross-linking agents such as diepoxybutane and mitomycin C. Somatic-cell hybridisation analysis of FA cell lines has demonstrated the existence of at least five complementation groups (FA-A to FA-E)2,3, the most common of which is FA-A4. This genetic heterogeneity has been a major obstacle to the positional cloning of FA genes by classical linkage analysis. The FAC gene was cloned by functional complementation5, and localised to chromosome 9q22.3 (ref. 2), but this approach has thus far failed to yield the genes for the other complementation groups. We have established a panel of families classified as FA-A by complementation analysis, and used them to search for the FAA gene by linkage analysis. We excluded the previous assignment by linkage6 of an FA gene to chromosome 20q, and obtained conclusive evidence for linkage of FAA to microsatellite markers on chromosome 16q24.3. Strong evidence of allelic association with the disease was detected with the marker D16S303 in the Afrikaner population of South Africa, indicating the presence of a founder effect.
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