A highly polymorphic locus cloned from the breakpoint of a chromosome 11p13 deletion associated with the WAGR syndrome

Thomas M Glaser, D. J. Driscoll, Stylianos Antonarakis, David Valle, David Housman

Research output: Contribution to journalArticle

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Abstract

Children with constitutional deletions of chromosome 11p13 suffer from aniridia, genitourinary malformations, and mental retardation and are predisposed to develop bilateral Wilms tumor (the WAGR syndrome). The critical region for these defects has been narrowed to a segment of band 11p13 between the catalase and the β-follicle-stimulating hormone genes. In this report, we have cloned the endpoints from a WAGR patient whose large cytogenetic deletion, del(11)(p14.3::p13), does not include the catalase gene. The deletion was characterized using DNA polymorphisms and found to originate in the paternally derived chromosome 11. The distal endpoint was identified as a rearrangement of locus D11S21 in conventional Southern blots of the patient's genomic DNA, but was not detected in leukocyte DNA from either parent or in sperm DNA from the father. The proximal endpoint was isolated by cloning the junction fragment and was mapped in relation to other markers and breakpoints. It defines a new locus in 11p13-ΔJ, which is close to the Wilms tumor gene and the breakpoint cluster region (TCL2) of the frequent t(11;14)(p13;q11) translocation in acute T-cell leukemia. An unusual concentration of base pair substitutions was discovered at ΔJ, in which 9 of 44 restriction sites tested (>20%) vary in the population. This property makes ΔJ one of the most polymorphic loci on chromosome 11 and may reflect an underlying instability that contributed to the original mutation. The breakpoint extends the genetic map of this region and provides a useful marker for linkage studies and the analysis of allelic segregation in tumor cells.

Original languageEnglish (US)
Pages (from-to)880-893
Number of pages14
JournalGenomics
Volume5
Issue number4
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

WAGR Syndrome
Chromosome Deletion
Chromosomes, Human, Pair 11
DNA
Catalase
Wilms' Tumor Genes
Aniridia
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Wilms Tumor
Follicle Stimulating Hormone
Multigene Family
Southern Blotting
Cytogenetics
Fathers
Base Pairing
Intellectual Disability
Genes
Spermatozoa
Organism Cloning
Leukocytes

ASJC Scopus subject areas

  • Genetics

Cite this

A highly polymorphic locus cloned from the breakpoint of a chromosome 11p13 deletion associated with the WAGR syndrome. / Glaser, Thomas M; Driscoll, D. J.; Antonarakis, Stylianos; Valle, David; Housman, David.

In: Genomics, Vol. 5, No. 4, 1989, p. 880-893.

Research output: Contribution to journalArticle

Glaser, Thomas M ; Driscoll, D. J. ; Antonarakis, Stylianos ; Valle, David ; Housman, David. / A highly polymorphic locus cloned from the breakpoint of a chromosome 11p13 deletion associated with the WAGR syndrome. In: Genomics. 1989 ; Vol. 5, No. 4. pp. 880-893.
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