Lima M, Mayer F M, Coutinho P, Abade A
Department of Biology, University of the Azores, São Miguel, Portugal.
Hum Biol. 1998 Dec;70(6):1011-23.
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder of adult onset. In the islands of the Azores (Portugal), MJD reaches the highest prevalence reported worldwide. It has been postulated that it is highly represented in the Azorean population as a result of a founder effect. To test this hypothesis, we reconstructed the ascending genealogies of the 32 Azorean families presently identified as harboring the disease (103 patients), using parish records as the main source of data. These patients were originally from the islands of São Miguel, Terceira, Graciosa, and Flores. The genealogies of the two main Azorean American families (Machado and Joseph) were also reconstructed. To identify the links between the MJD families, we calculated the kinship coefficient between the proponents of these genealogies. The family from Terceira was linked to three different MJD families from Flores through common ancestors. No kinship was observed between the MJD families from São Miguel and families from any other island. Links between the two Azorean American families and Azorean MJD families were found. The founders present in more than one ascendance were identified. Their chronological and geographic distribution indicates that more than one MJD mutation was introduced in the Azores, probably by settlers coming from the Portuguese mainland. The molecular evidence to date corroborates these results, because two distinct haplotypes have been established, one on the island of São Miguel and the other on Flores. Therefore molecular biology studies confirm the accuracy of the conclusions drawn from the genealogical evidence supporting the absence of a founder effect for MJD in the Azorean population.
马查多-约瑟夫病（MJD）是一种成年起病的常染色体显性神经退行性疾病。在亚速尔群岛（葡萄牙），MJD的患病率达到了全球报道的最高水平。据推测，由于奠基者效应，它在亚速尔群岛人群中高度富集。为了验证这一假设，我们以教区记录为主要数据来源，重建了目前已确定的32个患有该疾病的亚速尔群岛家族（103名患者）的上升系谱。这些患者最初来自圣米格尔岛、特塞拉岛、格拉西奥萨岛和弗洛雷斯岛。我们还重建了两个主要的亚速尔裔美国家族（马查多家族和约瑟夫家族）的系谱。为了确定MJD家族之间的联系，我们计算了这些系谱支持者之间的亲缘系数。特塞拉岛的家族通过共同祖先与弗洛雷斯岛的三个不同MJD家族有联系。在圣米格尔岛的MJD家族与来自其他任何岛屿的家族之间未观察到亲缘关系。发现了两个亚速尔裔美国家族与亚速尔群岛MJD家族之间的联系。确定了在不止一代中出现的奠基者。他们的时间和地理分布表明，在亚速尔群岛引入了不止一种MJD突变，可能是由来自葡萄牙大陆的定居者引入的。迄今为止的分子证据证实了这些结果，因为已经确定了两种不同的单倍型，一种在圣米格尔岛，另一种在弗洛雷斯岛。因此，分子生物学研究证实了从系谱证据得出的结论的准确性，这些证据支持亚速尔群岛人群中MJD不存在奠基者效应。
