Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1990-02

AUTHORS

Manfred Gessler, Annemarie Poustka, Webster Cavenee, Rachael L. Neve, Stuart H. Orkin, Gail A. P. Bruns

ABSTRACT

CYTOGENETIC analysis has identified chromosome Ilpl3 as the smallest overlap region for deletions found in individuals with WAGR syndrome, which includes Wilms tumour (a recessive childhood nephroblastoma), anirida, genito-urinary abnormalities and mental retardation1. The underlying loci have since been resolved into an aniridia (AN2) locus at a telomeric position, and a locus of closely spaced genes or a single pleiotropic gene involved in genito-urinary tract abnormalities and Wilms tumour at a more centromeric position2–7. Pulsed-field gel analysis of the 11pl3 region has revealed the presence of several putative CpG islands8,9, structures which are frequently associated with the 5' ends of expressed sequences, mainly housekeeping genes and some tissue-specific genes10. Starting from a CpG island, we have now isolated four neighbouring CpG islands, all within 650 kilobases (kb), by means of two consecutive bidirectional jumps in rare-cutting restriction-enzyme jumping libraries11. In two instances, flanking sequences were conserved in other species and RNA transcripts were identified. A complementary DNA clone isolated for one of them derives from an RNA highly expressed in fetal kidney, and is predicted to encode a Krüppel-like12 zinc-finger protein that is probably a transcription factor. The entire cDNA region is included in two partially overlapping homozygous deletions found in Wilms tumour DNA samples. Cloning of the breakpoints in one tumour revealed a deletion size of 170 kb, one-third of which is covered by the cDNA. The expression pattern and sequence of this cDNA could point to an important role for its corresponding gene in the normal development of the renal system as well as in Wilms tumour. More... »

PAGES

774-778

Journal

TITLE

Nature

ISSUE

6260

VOLUME

343

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/343774a0

    DOI

    http://dx.doi.org/10.1038/343774a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1028173278

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/2154702


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