Summary
We have analysed karyotypes and DNA from three patients with aniridia (congenital absence of irises) and Wilms' tumour. All three had constitutional deletions from the short arm of chromosome 11. The minimum region of overlap of the deletion involves a small region of band 11p13 presumed to contain the genetic loci responsible for both phenotypic abnormalities. Using cells from these patients, somatic cell hybrids with transformed mouse cells have been prepared. Individual subclones retaining either the deletion-11 chromosome or the normal chromosome 11, in addition to a variety of other human chromosomes, have been identified. The relative position of these breakpoints have been determined and the panel of hybrids has been used to map randomly-isolated 11p13 DNA sequences. The characterisation of these deletions has provided a useful panel of hybrids for random mapping strategies designed to identify the Wilms' and aniridia genes.
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References
Andersen S, Geertingen P, Larsen HW, Mikkelson M, Parbing A, Vestermark S, Warburg M (1978) Aniridia, cataract and gonadoblastoma in a mentally retarded girl with deletion of chromosome 11. Ophthalmologica 176:171–177
Bickmore W, Christie S, Van Heyningen V, Hastie ND, Porteous DJ (1988) Hitch-hiking from HRAS1 to the WAGR locus with CMGT markers. Nucleic Acids Res 16:51–60
Chiang YL, Ley TJ, Sanders-Haigh L, Anderson WF (1984) Human globin gene expression in hybrid 2S MEL x human fibroblast cells. Somatic Cell Mol Genet 10:399–407
Cowell JK (1980) Consistent chromosome abnormalities associated with mouse bladder epithelial cell lines transformed in vitro. JNCI 65:955–961
Cowell JK (1982) Appearance of double minute chromosome in somatic cell hybridisation experiments involving the HAT selection system. Cell Biol Int Rep 6:393–399
Cowell JK (1985) Tracking the cancer genes in paediatric predisposition syndromes; opportunities for prenatal diagnosis. Cancer Surv 3:573–601
Cowell JK (1986) Manipulation of somatic cell hybrids for the analysis of the human genome. In: Rooney DE, Czepulkowski BH (eds) Human cytogenetics, a practical approach. IRL Press, Oxford, pp 202–218
Cowell JK, Wadey RB, Little PFR (1987) Isolation and regional localisation of unique sequences from a chromosome 11 specific cosmid library. (9th International Workshop on Human Gene Mapping). Cytogenet Cell Genet 46:599 (abstr)
Drash A, Sherman F, Hartman WH, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms' tumour, hypertension, and degenerative renal disease. J Pediatr 76:585–593
Fearon ER, Vogelstein B, Feinberg AP (1984) Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours. Nature 309:176–178
Francke U, Holmes LB, Atkins L, Riccardi VM (1979) Aniridia-Wilms' tumour association; evidence for specific deletion of 11p13. Cytogenet Cell Genet 24:185–192
Glaser T, Lewis WH, Bruns GAP, Watkins PC, Rogler CE, Shows TB, Powers VE, Willard HF, Goguen JM, Simola KOJ, Housman DE (1986) β-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms' tumour, allowing a further definition of the WAGR locus. Nature 321:882–887
Howell RT, Gardner A, Dickinson V (1987) G and R banding of 11p deletions in aniridia-Wilms' tumour. J Med Genet 24:114–115
Huff V, Compton D, Lewis W, Jones C, Strong LC, Saunders GF (1987) An EcoRI polymorphism associated with a human genomic clone from band 11p13. Nucleic Acids Res 15:7651
Junien C, Turleau C, Grouchy J de, Said R, Rethore MO, Tenconi R, Dufier JL (1980) Regional assignment of catalase (CAT) gene to band 11p13. Association with the aniridia-Wilms' tumour-gonadoblastoma (WAGR) complex. Ann Génét (Paris) 28:165–168
Katz F, Povey S, Parkar M, Schneider C, Sutherland R, Stanley K, Solomon E, Greaves M (1983) Chromosome assignment of monoclonal antibody-defined determinants on human leukemic cells. Eur J Immunol 13:1008–1013
Knudson AG, Strong LC (1972) Mutation and cancer: a model for Wilms' tumour of the kidney. JNCI 40:313–324
Koufos A, Hansen MF, Lampkin BC, Workman ML, Copeland NG, Jenkins NA, Cavenee WK (1984) Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour. Nature 309:170–172
Lewis WH, Goguen JM, Powers VE, Willard HF, Michalopoulos EE (1985) Gene order on the short arm of human chromosome 11: regional assignment of the LDH A gene distal to catalase in two translocations. Hum Genet 71:249–253
Narahara K, Kikkawa K, Kimira S, Kimoto H, Ogata M, Kasai M, Matsuoka K (1984) Regional mapping of catalase and Wilms' tumour-aniridia, genitourinary abnormalities, and mental retardation triad loci to the chromosome segment 11p1305–p1306. Hum Genet 66:181–185
Orkin SH, Goldman DS, Sallan SE (1984) Development of homozygosity for chromosome 11 p markers in Wilms' tumour. Nature 309:172–174
Porteous DJ, Bickmore W, Christie S, Boyd PA, Cranston G, Fletcher JM, Gosden JR, Rout D, Seawright A, Simola KJO, Van Heyningen V, Hastie ND (1987) HRAS-1 selected chromosome transfer generates markers that colocalise aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms' tumour gene within band 11p13. Proc Natl Acad Sci USA 84:5355–5359
Quan F, Korneluk RG, Tropak MB, Gravel RA (1986) Isolation and characterization of the human catalase gene. Nucleic Acids Res 14:5321–5335
Riccardi VM, Sujansky E, Smith AC, Francke U (1978) Chromosome imbalance in the aniridia-Wilms' tumour association: 11p interstitial deletion. Pediatrics 61:604–610
Shannon RS, Mann JR, Harper E, Harnden DG, Morten JEN, Herbert A (1982) Wilms' tumour and aniridia: clinical and cytogenetic features. Arch Dis Child 57:685–690
Simola KOJ, Knuutila S, Kaitila I, Pirkola A, Pohja P (1983) Familial aniridia and translocation t(4;11)(q22;p13) without Wilms' tumour. Hum Genet 63:158–161
Turleau C, Grouchy J de, Nihoul-Fekete C, Dufier JL, Chavin-Colin F, Junien C (1984) Del 11p13/nephroblastoma without aniridia. Hum Genet 67:455–456
Van Heyningen V, Boyd PA, Seawright A, Fletcher JM, Fantes JA, Buckton KE, Spowart G, Porteous DJ, Hill RE, Newton MS, Hastie ND (1985) Molecular analysis of chromosome 11 deletions in aniridia-Wilms tumour syndrome. Proc Natl Acad Sci USA 82: 8592–8596
Watkins PC, Eddy R, Beck A, Vellucci V, Leverone B, Tanzi J, Gusella J, Shows T (1987) DNA sequence and regional assignment of the gene for the beta subunit of follicle-stimulating hormone to the short arm of chromosome 11. DNA 6:205–212
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Cowell, J.K., Wadey, R.B., Buckle, B.B. et al. The aniridia-Wilms' tumour association: molecular and genetic analysis of chromosome deletions on the short arm of chromosome 11. Hum Genet 82, 123–126 (1989). https://doi.org/10.1007/BF00284042
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DOI: https://doi.org/10.1007/BF00284042