A human-specific polymorphism in the coding region of the aggrecan gene - Variable number of tandem repeats produce a range of core protein sizes in the general population
A human-specific polymorphism in the coding region of the aggrecan gene - Variable number of tandem repeats produce a range of core protein sizes in the general population
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DOI：
10.1074/jbc.272.21.13974
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发表时间：
1997-05-23
影响因子：
4.8
通讯作者：
Wood, JG
中科院分区：
文献类型：
--
作者：
Doege, KJ;Coulter, SN;Wood, JG
聚集蛋白聚糖是软骨的主要结构基因之一，其编码蛋白聚糖核心蛋白，该蛋白聚糖核心蛋白由延伸的中央糖胺聚糖承载结构域组成，在每一端侧接球状结构域。中央区域由长段重复氨基酸组成，其充当糖胺聚糖如软骨素和硫酸角质素的附着位点;末端球状结构域与其它软骨成分相互作用。糖胺聚糖附着区在几个物种中由单个大外显子编码，其中有几种不同类型的重复序列。几个物种在该外显子内显示出用于附着硫酸软骨素的保守重复序列的类似块，但在人类中，该组重复序列特别保守。通过聚合酶链反应或Southern印迹分析对来自无关个体群体的基因组DNA的检查显示，该重复序列块以多种等位基因形式存在，其不同之处在于每个等位基因中该位点处的重复序列数目，13个不同的等位基因已被确定，与重复数范围从13到33，这是一个不寻常的例子，表达的串联重复多态性的可变数目，这种多态性显然是局限于人类，几个物种的检查，这种多态性的结果在不同长度的聚集蛋白聚糖核心蛋白的个人，轴承不同数量的潜在附着硫酸软骨素位点。存在的可能性为软骨功能特性的生物变异的分子理解。
Aggrecan, one of the major structural genes of cartilage, encodes a proteoglycan core protein composed of an extended central glycosaminoglycan bearing domain, flanked by globular domains at each end, The central region consists of long stretches of repeating amino acids that serve as attachment sites for glycosaminoglycans such as chondroitin and keratan sulfate; the terminal globular domains interact with other cartilage components, The glycosaminoglycan attachment region is encoded in several species by a single large exon, within which are several different types of repeating sequences. Several species show within this exon a similar block of conserved repeats for attachment of chondroitin sulfate, but in humans this group of repeats is particularly well conserved, Examination of genomic DNA from a population of unrelated individuals by polymerase chain reaction or Southern blot assays shows this block of repeat sequences exists in multiple allelic forms, which differ by the number of repeats at this site in each allele, Thirteen different alleles have been identified, with repeat numbers ranging from 13 to 33, This is an unusual example of an expressed variable number of tandem repeat polymorphism, This polymorphism is apparently restricted to humans, of several species examined, This polymorphism results in individuals with differing length aggrecan core proteins, bearing different numbers of potential attachment sites for chondroitin sulfate. The possibility exists for a molecular understanding of biological variation in cartilage functional properties.