Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family
Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family
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DOI：
10.1101/gr.7.1.10
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发表时间：
1997-01-01
期刊：
影响因子：
7
通讯作者：
Lovett, M
中科院分区：
文献类型：
--
作者：
Wise, CA;Clines, GA;Lovett, M
遗传性多发性外生骨疣 (EXT) 是一种常染色体显性遗传疾病，其特征是长骨近骨骺区域的多个骨增生。在一小部分病例中，这些外生骨疣会进展为恶性软骨肉瘤。这种疾病的遗传连锁已被描述为染色体 8q24.1 (EXT1)、11p11-13 (EXT2) 和 19p (EXT-3) 上的三个独立位点。 EXT1 和 EXT2 基因最近被分离出来，并且彼此显示出广泛的序列同源性。这些基因在外生骨疣衍生的肿瘤中被删除，支持了它们编码肿瘤抑制因子的假设。我们已经鉴定出第三个基因，该基因在核苷酸和氨基酸序列水平上与 EXT1 和 EXT2 表现出惊人的序列相似性，并衍生出了其完整的编码序列。尽管该基因转录的 mRNA 大小与 EXT1 和 EXT2 相似，但其表达模式却截然不同。我们通过荧光原位杂交到中期染色体，并通过全基因组辐射杂交定位到 D15458 和 DIS511 之间的染色体 1p36.1（该区域在多种肿瘤类型中经常显示杂合性丢失）来定位该基因。因此，EXTL（EXT-like）基因是 EXT 基因家族的新成员，并且是多种疾病表型的潜在候选基因。
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 D15458 and DIS511, 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.