Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
BMC Med Genet. 2010 Mar 25;11:47. doi: 10.1186/1471-2350-11-47.
Machado-Joseph disease (MJD), caused by a CAG repeat expansion located in exon10 of the ATXN3 gene, is now regarded as one of the most common spinocerebellar ataxia (SCA) in the world. The relative frequency of MJD among SCA has previously been estimated at about 50% in the Chinese population and has been reported to be related to the frequency of large normal alleles in some populations. Taq polymerase has been used for PCR in nearly all studies reported previously.
Normal and expanded alleles of ATXN3 were detected via PCR using LA Taq DNA polymerase (better for GC-rich sequences) and denaturing polyacrylamide gel electrophoresis in 150 normal individuals and 138 unrelated probands from autosomal dominant SCA families. To compare reaction efficiency, 12 MJD patients' expanded alleles were amplified with La Taq and Taq polymerase respectively in the same amplifying systems and reaction conditions.
Normal alleles ranged from 12 to 42 CAG repeats. The most common allele contained 14 repeats with a frequency of 23.3%, which corroborates previous reports. The frequency of large normal alleles (>27 repeats) was 0.28, which was very high relative to previous reports. The frequency of MJD in SCA patients was 72.5%, which was significantly higher than those in previous reports about the Chinese and other Asian populations. This frequency was one of the highest reported worldwide, with only Portuguese and Brazilian populations exhibiting higher proportions. All 12 expanded alleles were amplified in PCR with La Taq polymerase, whereas only 2 expanded alleles were amplified with Taq polymerase.
We have first reported the highest relative frequency of MJD in Asia, and we attribute this high frequency to a more efficient PCR using LA Taq polymerase and hypothesized that large ANs may act as a reservoir for expanded alleles in the Southeastern Chinese population.
马查多-约瑟夫病（MJD）是由 ATXN3 基因外显子 10 中的 CAG 重复扩展引起的，现已被认为是世界上最常见的脊髓小脑共济失调（SCA）之一。在中国人中，MJD 在 SCA 中的相对频率此前估计约为 50%，并已报道与某些人群中正常大等位基因的频率有关。以前几乎所有研究都使用 Taq 聚合酶进行 PCR。
使用 LA Taq DNA 聚合酶（更适合 GC 丰富的序列）和变性聚丙烯酰胺凝胶电泳，在 150 名正常个体和 138 名常染色体显性 SCA 家族的无关先证者中检测 ATXN3 的正常和扩展等位基因。为了比较反应效率，在相同的扩增系统和反应条件下，使用 La Taq 和 Taq 聚合酶分别扩增了 12 名 MJD 患者的扩增等位基因。
正常等位基因范围为 12 至 42 个 CAG 重复。最常见的等位基因包含 14 个重复，频率为 23.3%，与之前的报道一致。大正常等位基因（>27 个重复）的频率为 0.28，与之前的报道相比非常高。SCA 患者中 MJD 的频率为 72.5%，明显高于之前关于中国和其他亚洲人群的报道。这一频率是世界上报道的最高频率之一，只有葡萄牙和巴西人群的比例更高。所有 12 个扩展等位基因均在使用 La Taq 聚合酶的 PCR 中扩增，而只有 2 个扩展等位基因在使用 Taq 聚合酶的 PCR 中扩增。
我们首次报道了亚洲最高的 MJD 相对频率，我们将这种高频率归因于使用 LA Taq 聚合酶进行更有效的 PCR，并假设大 AN 可能在东南中国人群中作为扩展等位基因的储库。
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