Human protein tyrosine phosphatase-like gene: expression profile, genomic structure, and mutation analysis in families with ARVD
Human protein tyrosine phosphatase-like gene: expression profile, genomic structure, and mutation analysis in families with ARVD
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DOI：
10.1016/s0378-1119(00)00347-4
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发表时间：
2000-10-03
期刊：
影响因子：
3.5
通讯作者：
Roberts, R
中科院分区：
文献类型：
--
作者：
Li, DX;Gonzalez, O;Roberts, R
最近克隆了小鼠蛋白质酪氨酸磷酸酶样基因（Ptpla），数据表明它在肌肉发生和心脏发生中发挥作用。人类同源基因（PTPLA）定位于染色体10 p13 -14，我们已经定位了一个基因座，负责致心律失常性右心室发育不良（ARVD）的区域。作为一个位置候选基因，我们通过确定PTPLA的组织表达、基因组结构来表征PTPLA，我们还筛选了ARVD患者的突变。北方分析表明PTPLA在成人和胎儿心脏中优先表达。在骨骼肌和平滑肌组织中检测到低得多的表达。在其他组织中几乎没有观察到表达。PTPLA的蛋白质编码序列由7个外显子组成。在一个ARVD家系中发现一个Lys 64 Gln的序列变异。然而，在正常对照受试者中也检测到相同的变异（3个等位基因/100条染色体）。因此，变异体（Lys 64 Gln）与我们家族的ARVD无关，是一种良性多态性。然而，其在发育和成年心脏中的组织特异性表达表明PTPLA在调节心脏发育、分化或其他细胞事件中具有作用。PTPLA的基因组结构和基因内多态性为PTPLA的基因打靶等临床和遗传学研究奠定了基础。(C)2000 Elsevier Science B. V.保留所有权利。
The mouse protein tyrosine phosphatase-like gene (Ptpla) was recently cloned and data suggested that it plays a role in myogenesis and cardiogenesis. The human homologue (PTPLA) was mapped to chromosome 10p13-14, a region where we have mapped a locus responsible for arrhythmogenic right ventricular dysplasia (ARVD). As a positional candidate gene, we characterized PTPLA by determining its tissue expression, its genomic structure, and we also screened for mutations in the ARVD patients. Northern analysis demonstrated PTPLA is preferentially expressed in both adult and fetal heart. A much lower expression was detected in skeletal and smooth muscle tissues. Virtually no expression was observed in other tissues. The protein-encoding sequences of PTPLA consist of seven exons. A sequence variation (Lys64Gln) was found in all the affecteds in a large ARVD family. However, the same variant was also detected in normal control subjects (three alleles/100 chromosomes). Thus, the variant (Lys64Gln) is not responsible for ARVD in our family and is a benign polymorphism. Nevertheless, its tissue-specific expression in the developing and adult heart suggest PTPLA has a role in regulating cardiac development, differentiation, or other cellular events. The genomic structure and intragenic polymorphism of PTPLA should be useful for further clinical and genetic studies such as gene targeting of PTPLA. (C) 2000 Elsevier Science B.V. All rights reserved.