Identification of a novel human gene containing the tetratricopeptide repeat domain from the Down syndrome region of chromosome 21.
Identification of a novel human gene containing the tetratricopeptide repeat domain from the Down syndrome region of chromosome 21.
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DOI：
10.1093/dnares/3.1.9
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发表时间：
1996-02-29
期刊：
影响因子：
--
通讯作者：
Ohki, M
中科院分区：
文献类型：
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作者：
Ohira, M;Ootsuyama, A;Ohki, M
通过对患有部分21三体的唐氏综合征患者的分析，确定了21号染色体上的唐氏综合征（DS）区域，该区域负责唐氏综合征的主要特征。在DS区域内，我们之前构建了1.6 mb的P1序列图。为了从1.6 mb区域分离基因片段，我们利用P1克隆和人胎脑cDNA文库进行了直接cDNA文库筛选和外显子捕获，获得了67个cDNA片段和52个可能的外显子。其中23个cDNA片段和4个外显子通过P1克隆定位和Northern分析被解释为来自单个基因。为了获得全长cDNA序列，从另一个富含较长cDNA物种的人cDNA文库中进一步筛选较长的cDNA克隆。对这些克隆进行测序和组装，得到一个9045 bp的序列。该转录序列编码一种含有四肽重复序列（TPR）基序的新型2025氨基酸蛋白，因此该基因被命名为TPRD（一种含有唐氏综合征区域TPR基序的基因）。在某些蛋白质磷酸酶和其他参与RNA合成或有丝分裂调节的蛋白质中发现了TPR结构域。TPRD基因是一个新的基因，被证明位于1.6 mb区域，具有上述有趣的特征，是负责DS表型的候选基因。
The Down syndrome (DS) region on chromosome 21, which is responsible for the DS main features, has been defined by analysis of DS patients with partial trisomy 21. Within the DS region, we constructed a 1.6-Mb P1 contig map previously. To isolate gene fragments from the 1.6-Mb region, we performed direct cDNA library screening and exon trapping using the P1 clones and a human fetal brain cDNA library, and obtained 67 cDNA fragments and 52 possible exons. Among them, 23 cDNA fragments and 4 exons were interpreted to be derived from a single gene by localization on P1 clones and by Northern analysis. To obtain the full-length cDNA sequence, longer cDNA clones were further screened from another human cDNA library which was enriched with longer cDNA species. These clones were sequenced and assembled to a sequence of 9045 bp. This transcribed sequence encodes a novel 2025 amino-acid protein containing tetratricopeptide repeat (TPR) motifs and therefore the gene was designated as TPRD (a gene containing the TPR motifs on the Down syndrome region). The TPR domain has been found in a certain protein phosphatase and in other proteins involved in the regulation of RNA synthesis or mitosis. The TPRD gene, the novel gene which was proved to be in the 1.6-Mb region and to have the interesting features described above, is a candidate for genes responsible for the DS phenotypes.