Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles
Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles
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DOI：
10.1038/ejhg.2011.154
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发表时间：
2012-01-01
影响因子：
5.2
通讯作者：
Rodriguez Labrada, Roberto
中科院分区：
文献类型：
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作者：
Miguel Laffita-Mesa, Jose;Velazquez-Perez, Luis C.;Rodriguez Labrada, Roberto
共济失调蛋白-2基因的短、大或中等正常等位基因（AN）在产生导致脊髓小脑共济失调2型（SCA 2）的扩展等位基因（EA）中的作用知之甚少。据推测，SCA 2患病率与大AN的频率有关。SCA 2在古巴人群中显示出最高的全球患病率，因此这是研究大等位基因和中等等位基因频率与SCA 2突变频率之间关系的独特来源。通过在一个全面的样本（类似于3000条染色体）的遗传多态性分析，我们表明，在ataxin-2基因的大AN的频率是世界上最高的，虽然短AN也很常见。这种高度多态性的群体在CAG序列中也显示出高变异性，其特征在于锚CAA中断的丢失。此外，大的AN表现出germination和躯体不稳定性。我们的研究还包括相关的基因型，系谱和单倍型数据，并提供了大量的证据方面的作用，大和中间等位基因的病理性EA的产生。European Journal of Human Genetics（2012）20，41-49; doi：10.1038/ejhg.2011.154; 2011年9月21日在线发表
The role of short, large or intermediate normal alleles (ANs) of the ataxin-2 gene in generating expanded alleles (EAs) causing spinocerebellar ataxia type 2 (SCA2) is poorly understood. It has been postulated that SCA2 prevalence is related to the frequency of large ANs. SCA2 shows the highest worldwide prevalence in Cuban population, which is therefore a unique source for studying the relationship between the frequency of large and intermediate alleles and the frequency of SCA2 mutation. Through genetic polymorphism analyses in a comprehensive sample (similar to 3000 chromosomes), we show that the frequency of large ANs in the ataxin-2 gene is the highest worldwide, although short ANs are also frequent. This highly polymorphic population displayed also high variability in the CAG sequence, featured by loss of the anchor CAA interruption(s). In addition, large ANs showed germinal and somatic instability. Our study also includes related genotypic, genealogical and haplotypic data and provides substantial evidence with regard to the role of large and intermediate alleles in the generation of pathological EAs. European Journal of Human Genetics (2012) 20, 41-49; doi:10.1038/ejhg.2011.154; published online 21 September 2011