Veneziano Liana, Mantuano Elide, Catalli Claudio, Gellera Cinzia, Durr Alexandra, Romano Silvia, Spadaro Maria, Frontali Marina, Novelletto Andrea
Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy.
J Hum Genet. 2014 Mar;59(3):153-7. doi: 10.1038/jhg.2013.137. Epub 2014 Jan 9.
To clarify the population history of dentatorubropallidoluysian atrophy (DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers.
为了阐明意大利齿状核红核苍白球路易体萎缩症（DRPLA）的群体历史并追溯该突变的引入时间，我们重建了10名意大利裔患者中CAG重复序列侧翼的扩展单倍型，分析它们与CAG重复序列距离的相似性/差异性。我们的目的是将连接所有观察到的单倍型的单一、近期谱系假说与来自外部来源的更远缘相关单倍型多次引入的替代假说进行比较。选择多态性DNA标记覆盖CAG重复序列侧翼153 kb的区域，这对于确定不受重组影响的DNA片段的年龄具有信息价值。在所有患者中，均证实ATN1 CAG片段发生了扩增，且位于与日本和葡萄牙人群中CAG扩增相关的同一狭窄单倍型上。我们还观察到在CAG两侧更远距离处DRPLA单倍型的破坏。我们的结果与过去600年内单一奠基者的情况相符，最有可能是在过去270年之前。对西西里人群的这些估计在很大程度上与葡萄牙航海旅行者可能引入携带DRPLA突变的日本单倍型的时期重叠。
