Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family

Carol A. Wise, Gregory A. Clines, Hillary Massa, Barbara J. Trask, Michael Lovett

Research output: Contribution to journalArticle

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Abstract

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by multiple bony outgrowths from the juxtaepiphyseal region of long bones. In a small proportion of cases, these exostoses progress to malignant chondrosarcomas. Genetic linkage of this disorder has been described to three independent loci on chromosomes 8q24.1 (EXT1), 11p11-13 (EXT2), and 19p (EXT-3). The EXT1 and EXT2 genes were isolated recently and show extensive sequence homology to each other. These genes are deleted in exostoses-derived tumors, supporting the hypothesis that they encode tumor suppressors. We have identified a third gene that shows striking sequence similarity to both EXT1 and EXT2 at the nucleotide and amino acid sequence levels, and have derived its entire coding sequence. Although the mRNA transcribed from this gene is similar in size to that from EXT1 and EXT2, its pattern of expression is quite different. We have localized this gene by fluorescence in situ hybridization to metaphase chromosomes and by whole genome radiation hybrid mapping to chromosome 1p36.1 between D1S458 and D1S511, a region that frequently shows loss of heterozygosity in a variety of tumor types. This gene, EXTL (for EXT-like), is therefore a new member of the EXT gene family and is a potential candidate for several disease phenotypes.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalGenome Research
Volume7
Issue number1
StatePublished - Jan 1997

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Multiple Hereditary Exostoses
Exostoses
Genes
Chromosomes
Radiation Hybrid Mapping
Neoplasms
Inborn Genetic Diseases
Chondrosarcoma
Genetic Linkage
Loss of Heterozygosity
Metaphase
Sequence Homology
Fluorescence In Situ Hybridization
Amino Acid Sequence
Nucleotides
Genome
Phenotype
Bone and Bones
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. / Wise, Carol A.; Clines, Gregory A.; Massa, Hillary; Trask, Barbara J.; Lovett, Michael.

In: Genome Research, Vol. 7, No. 1, 01.1997, p. 10-16.

Research output: Contribution to journalArticle

Wise, Carol A. ; Clines, Gregory A. ; Massa, Hillary ; Trask, Barbara J. ; Lovett, Michael. / Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. In: Genome Research. 1997 ; Vol. 7, No. 1. pp. 10-16.
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