人类Batten病基因CLN_3及其突变的生物信息学分析  

Bioinformatics analysis of human natten disease-associated gene CLN_3 and its mutation

作　　者：陈平[1] 张高川[1] 王文兵[2] 李新平[1] 朱江[1] 

机构地区：[1]苏州大学生命科学学院,江苏苏州215123 [2]江苏大学生命科学研究院,江苏镇江212013

出　　处：《苏州大学学报（自然科学版）》2008年第1期85-90,共6页Journal of Soochow University(Natural Science Edition)

基　　金：国家自然科学基金资助项目(30471250)

摘　　要：利用生物信息学方法对与儿童蜡样质脂褐质沉积症（NCLs）相关基因CLN3，的结构进行了深入的分析．根据CLN3的mRNA序列对其进行了染色体精确定位，确定CLN3的ORF及其外显子的位置；分析CLN3蛋白质（CLN 3P）结构特点和修饰位点，并明确近缘种及远缘种的保守区域和突变致病的关系．结果表明，CLN3位于人类16号染色体的短臂（16（p12．1～p11．2））；基因全长为14804bp，包含15个外显子和14个内含子，ORF长度1317bp，编码438个氨基酸．蛋白质功能域分析表明，CLN 3P是一种分子量为43kDa的高度糖基化的溶酶体膜蛋白，该蛋白存在酰基化、糖基化和多种磷酸化修饰位点，在近缘的CLN 3P中存在高度保守的区域，进一步对10个远缘蛋白的多序列进行比对，发现了该蛋白质中最为保守的区域；45种CLN 3P的突变分析显示，主要的突变位于101、161～162、170、187、199、211、295、327、330、334、352等12个氨基酸位点，这些突变几乎发生在保守区域，突变还表现出一定的分布特点及地区差异，说明保守序列的突变是该疾病产生的重要原因，为该病的分子诊断提供了依据．By the method of bioinformatics,the structure of CLN3 which was associated with a disease called juvenile neuronal ceroid lipofuscinosis（NCLs） （also known as Batten disease）was analyzed. Based on the mRNA sequence,the ORF and the location of exons and introns on the chromosome were determined. The results showed that the CLN3 gene locates on the 16 chromosome of human（ 16（ p11. 2 -p12.1 ））and has full length of 14804 base pairs, including 15 exons and 14 introns. The length of ORF is 1317 base pairs,which encoded 438 amino acids. The protein domain analysis showed that the CLN 3P was a glycosylated lysosomal membrane protein containing myristoylation,glycosylation,phosphorylation sites with a molecular weight 43kDa. There was a highly conserved region in the CLN 3P of Orthologs. Furthermore,with the multi-alignment of CLN 3 P in distant homologs,we find the most conserved region in the sequence. The analysis of 45 mutant sites indicates that the main mutant sites locate on 12 amino acids sites, such as 101、161 -162、170、187、199、211、295、327、330、334 and 352,which all occur in the conserved regions. Meanwhile,mutations in the sequence presenting some distribution characteric and region distinction, demonstrate mutations in conserved sequences maybe the key reason for the disease ,which provides the according of the molecular diagnosis.

关 键 词：蜡样质脂褐质沉积症 CLN3 生物信息学 保守区域 修饰位点 突变 

分 类 号：Q503[生物学—生物化学]