Alvarez Gonzalo, Ceballos Francisco C, Quinteiro Celsa
Departamento de Genética, Facultad de Biología, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain.
PLoS One. 2009;4(4):e5174. doi: 10.1371/journal.pone.0005174. Epub 2009 Apr 15.
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.
西班牙哈布斯堡王朝（1516 - 1700年）的国王们经常近亲结婚，叔侄、表亲及其他血亲结合在该王朝十分普遍。历史文献表明，近亲繁殖是导致该王朝覆灭的主要原因，因为国王查理二世身心残疾，于1700年去世，且他的两段婚姻均未留下子嗣，但这一假设尚未从遗传学角度进行检验。在本文中，通过计算西班牙哈布斯堡王朝国王们的近亲繁殖系数（F）来验证这一假设，所依据的扩展谱系深入至16代，涉及3000多人。西班牙哈布斯堡王朝国王们的近亲繁殖系数随世代显著增加，从王朝奠基人腓力一世的0.025增至查理二世的0.254，该王朝的几位成员近亲繁殖系数高于0.20。除了近亲结合导致的近亲繁殖外，来自多个远祖的祖先近亲繁殖对多数国王的近亲繁殖系数也有很大贡献。在西班牙哈布斯堡王朝国王们的后代中，检测到了对活到10岁具有统计学显著意义的近亲繁殖衰退现象。结果表明，表亲水平的近亲繁殖（F = 0.0625）对存活率产生了17.8%±12.3%的负面影响。据推测，查理二世（F = 0.254）同时患有两种不同的遗传疾病：联合垂体激素缺乏症和远端肾小管酸中毒，这两种疾病由两个不连锁基因座上的隐性等位基因决定，这可以解释这位国王复杂的临床症状，包括他的阳痿/不育，最终导致了王朝的覆灭。
