A MAJOR SEGMENT OF THE NEUROFIBROMATOSIS TYPE-1 GENE - CDNA SEQUENCE, GENOMIC STRUCTURE, AND POINT MUTATIONS
A MAJOR SEGMENT OF THE NEUROFIBROMATOSIS TYPE-1 GENE - CDNA SEQUENCE, GENOMIC STRUCTURE, AND POINT MUTATIONS
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DOI：
10.1016/0092-8674(90)90253-b
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发表时间：
1990-07-13
期刊：
影响因子：
64.5
通讯作者：
WHITE, R
中科院分区：
文献类型：
--
作者：
CAWTHON, RM;WEISS, R;WHITE, R
最近在神经纤维瘤病1型基因座发现易位断点区（TBR）基因的重叠cDNA克隆，并发现被缺失和t（17;22）易位中断，已被测序。已将TBR基因转录物的4kb序列与基因组DNA序列进行了比较，鉴定了许多小外显子。剪接点和一个大的开放阅读框的鉴定表明，该基因的5“端朝向着丝粒，与该区域的三个已知活性基因相反。PCR扩增的一个子集的外显子，然后通过电泳变性产物的天然凝胶，确定了6个变异构象特异性NF 1患者，表明在基因中的碱基对的变化。测序显示，一个突变等位基因含有T →。C转换将亮氨酸变为脯氨酸;另一个NF 1等位基因具有C →。将精氨酸转变为终止密码子的T转变。这些结果确立了TBR基因为NF 1基因，并提供了该基因的主要片段的描述。
Overlapping cDNA clones from the translocation break-point region (TBR) gene, recently discovered at the neurofibromatosis type 1 locus and found to be interrupted by deletions and a t(17;22) translocation, have been sequenced. A 4 kb sequence of the transcript of the TBR gene has been compared with sequences of genomic DNA, identifying a number of small exons. Identification of splice junctions and a large open reading frame indicates that the gene is oriented with its 5'' end toward the centromere, in opposition to the three known active genes in the region. PCR amplification of a subset of the exons, followed by electrophoresis of denatured product on native gels, identified six variant conformers specific to NF1 patients, indicating base pair changes in the gene. Sequencing revealed that one mutant allele contains a T .fwdarw. C transition changing a leucine to a proline; another NF1 allele harbors a C .fwdarw. T transition changing an arginine to a stop codon. These results establish the TBR gene as the NF1 gene and provide a description of a major segment of the gene.