The Role of Inbreeding in the Extinction of a European Royal Dynasty
The Role of Inbreeding in the Extinction of a European Royal Dynasty
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DOI：
10.1371/journal.pone.0005174
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发表时间：
2009-04-15
期刊：
影响因子：
3.7
通讯作者：
Quinteiro, Celsa
中科院分区：
文献类型：
--
作者：
Alvarez, Gonzalo;Ceballos, Francisco C.;Quinteiro, Celsa
西班牙哈布斯堡王朝（1516-1700）的国王经常以近亲结婚的方式进行，叔侄女、堂表兄弟姐妹和其他近亲结合在该王朝很盛行。历史文献中曾有人认为近亲繁殖是王朝灭亡的主要原因，1700年身体和精神残疾的国王查理二世去世，他的两次婚姻都没有生育孩子，但这一假设尚未从遗传学角度得到检验。在本文中，通过计算西班牙哈布斯堡国王的近亲繁殖系数 (F)，从长达 16 代、涉及 3,000 多个个体的扩展谱系中验证了这一假设。西班牙哈布斯堡王朝国王的近亲繁殖系数逐代大幅增加，从王朝创始人菲利普一世国王的0.025到查理二世国王的0.254，并且该王朝的一些成员的近亲繁殖系数高于0.20。除了近亲之间的结合造成的近亲繁殖之外，来自多个远祖的近亲繁殖对大多数国王的近亲繁殖系数也做出了重大贡献。在西班牙哈布斯堡王朝国王的后代中发现了统计上显着的近亲繁殖衰退，生存期长达 10 年。结果表明，近亲繁殖（F = 0.0625）对生存率产生了 17.8% +/- 12.3 的不利影响。据推测，查理二世（F = 0.254）同时发生两种不同的遗传性疾病：联合垂体激素缺乏症和远端肾小管酸中毒，由两个不连锁基因座的隐性等位基因决定，可以解释这位国王的大部分复杂的临床特征，包括他的阳痿/不孕症，最终导致王朝的灭亡。
The kings of the Spanish Habsburg dynasty (1516-1700) frequently married close relatives in such a way that uncle-niece, first cousins and other consanguineous unions were prevalent in that dynasty. In the historical literature, it has been suggested that inbreeding was a major cause responsible for the extinction of the dynasty when the king Charles II, physically and mentally disabled, died in 1700 and no children were born from his two marriages, but this hypothesis has not been examined from a genetic perspective. In this article, this hypothesis is checked by computing the inbreeding coefficient (F) of the Spanish Habsburg kings from an extended pedigree up to 16 generations in depth and involving more than 3,000 individuals. The inbreeding coefficient of the Spanish Habsburg kings increased strongly along generations from 0.025 for king Philip I, the founder of the dynasty, to 0.254 for Charles II and several members of the dynasty had inbreeding coefficients higher than 0.20. In addition to inbreeding due to unions between close relatives, ancestral inbreeding from multiple remote ancestors makes a substantial contribution to the inbreeding coefficient of most kings. A statistically significant inbreeding depression for survival to 10 years is detected in the progenies of the Spanish Habsburg kings. The results indicate that inbreeding at the level of first cousin (F = 0.0625) exerted an adverse effect on survival of 17.8% +/- 12.3. It is speculated that the simultaneous occurrence in Charles II (F = 0.254) of two different genetic disorders: combined pituitary hormone deficiency and distal renal tubular acidosis, determined by recessive alleles at two unlinked loci, could explain most of the complex clinical profile of this king, including his impotence/infertility which in last instance led to the extinction of the dynasty.