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The role of inbreeding in the extinction of a European royal dynasty.

Alvarez G, Ceballos FC, Quinteiro C - PLoS ONE (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Genética, Facultad de Biología, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain. g.alvarez@usc.es

ABSTRACT
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.

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Survival to 10 years (prenatal and neonatal deaths not included) and inbreeding coefficient (F) in eight progenies of Spanish kings.
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Related In: Results  -  Collection


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pone-0005174-g004: Survival to 10 years (prenatal and neonatal deaths not included) and inbreeding coefficient (F) in eight progenies of Spanish kings.

Mentions: The effect of inbreeding on survival in the Spanish Habsburg dynasty is investigated from mortality data of eight royal families (Table 3). Two different regression analyses of survival to 10 years of the progenies of the eight royal families as a function of the inbreeding coefficients of the offspring and mother have been performed. One of these analyses is a multiple regression analysis computed by ordinary least squares and the other is a multiple logistic regression analysis based on logit-transformed data where parameter estimation is performed by maximum likelihood methods. When all pre- and postnatal losses are included in the calculation of survival to 10 years, a statistically significant effect of the inbreeding coefficient of the offspring on survival is detected by the multiple logistic regression and this inbreeding effect is very close to the statistical significance (P = 0.053) by the multiple regression by ordinary least squares (Table 4). When miscarriages, stillbirths and neonatal deaths are removed from the analysis, the inbreeding effect on survival to 10 years is more consistent and both multiple and logistic regressions show a clear inbreeding depression in the inbred offspring (Table 4 and Figure 4). On the other hand, an effect of maternal inbreeding on survival to 10 years is not detected by the regression analyses. These results suggest that the main effect of inbreeding on survival is produced in children between month 1 and year 10. In fact, it seems that inbreeding does not have a significant effect on early mortality (prenatal and neonatal deaths) in the Spanish Habsburg dynasty. Thus, a negative statistical association between prenatal losses (miscarriages and stillbirths) and inbreeding coefficient among families is detected by Kendall's coefficient of rank correlation but this association is not statistically significant (τ = −0.161, P = 0.595). Similarly, the association between neonatal deaths and inbreeding coefficient among families is not statistically significant (τ = −0.041, P = 0.833). These slight and non significant negative associations between early mortalities and inbreeding coefficient may be easily explained as a consequence of sampling errors due to small sample size (51 pregnancies in the eight families studied) and the possibility that inbreeding plays a protective role in early mortality must be considered a very unlikely hypothesis. The magnitude of the inbreeding depression in the Spanish Habsburg dynasty seems to be remarkable. Thus, under a simple linear regression model, the regression coefficient of survival to 10 years (prenatal and neonatal deaths not included) as a function of the inbreeding coefficient is −2.850±0.756 which is significantly lower than 1 (t = 3.771, P = 0.009 by a two sided test). This supposes that the impact of an F = 0.0625, corresponding to the progeny from a first cousin marriage, on survival is 17.8%±12.3. In present human populations the most recent estimate of inbreeding effect on the children of first cousin marriages is 4.4%±4.6 (depression of survival at age 10 including late miscarriages, stillbirths and neonatal deaths) based on a large data set of first cousins [21]. Although these two figures are not directly comparable since one refers to an inbreeding effect in a particular family and the other refers to an average effect for a large number of families in different populations they show that the reduction in survival at age 10 for a first cousin progeny with respect to the offspring from unrelated parents detected in the Spanish Habsburg families is very remarkable.


The role of inbreeding in the extinction of a European royal dynasty.

Alvarez G, Ceballos FC, Quinteiro C - PLoS ONE (2009)

Survival to 10 years (prenatal and neonatal deaths not included) and inbreeding coefficient (F) in eight progenies of Spanish kings.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664480&req=5

pone-0005174-g004: Survival to 10 years (prenatal and neonatal deaths not included) and inbreeding coefficient (F) in eight progenies of Spanish kings.
Mentions: The effect of inbreeding on survival in the Spanish Habsburg dynasty is investigated from mortality data of eight royal families (Table 3). Two different regression analyses of survival to 10 years of the progenies of the eight royal families as a function of the inbreeding coefficients of the offspring and mother have been performed. One of these analyses is a multiple regression analysis computed by ordinary least squares and the other is a multiple logistic regression analysis based on logit-transformed data where parameter estimation is performed by maximum likelihood methods. When all pre- and postnatal losses are included in the calculation of survival to 10 years, a statistically significant effect of the inbreeding coefficient of the offspring on survival is detected by the multiple logistic regression and this inbreeding effect is very close to the statistical significance (P = 0.053) by the multiple regression by ordinary least squares (Table 4). When miscarriages, stillbirths and neonatal deaths are removed from the analysis, the inbreeding effect on survival to 10 years is more consistent and both multiple and logistic regressions show a clear inbreeding depression in the inbred offspring (Table 4 and Figure 4). On the other hand, an effect of maternal inbreeding on survival to 10 years is not detected by the regression analyses. These results suggest that the main effect of inbreeding on survival is produced in children between month 1 and year 10. In fact, it seems that inbreeding does not have a significant effect on early mortality (prenatal and neonatal deaths) in the Spanish Habsburg dynasty. Thus, a negative statistical association between prenatal losses (miscarriages and stillbirths) and inbreeding coefficient among families is detected by Kendall's coefficient of rank correlation but this association is not statistically significant (τ = −0.161, P = 0.595). Similarly, the association between neonatal deaths and inbreeding coefficient among families is not statistically significant (τ = −0.041, P = 0.833). These slight and non significant negative associations between early mortalities and inbreeding coefficient may be easily explained as a consequence of sampling errors due to small sample size (51 pregnancies in the eight families studied) and the possibility that inbreeding plays a protective role in early mortality must be considered a very unlikely hypothesis. The magnitude of the inbreeding depression in the Spanish Habsburg dynasty seems to be remarkable. Thus, under a simple linear regression model, the regression coefficient of survival to 10 years (prenatal and neonatal deaths not included) as a function of the inbreeding coefficient is −2.850±0.756 which is significantly lower than 1 (t = 3.771, P = 0.009 by a two sided test). This supposes that the impact of an F = 0.0625, corresponding to the progeny from a first cousin marriage, on survival is 17.8%±12.3. In present human populations the most recent estimate of inbreeding effect on the children of first cousin marriages is 4.4%±4.6 (depression of survival at age 10 including late miscarriages, stillbirths and neonatal deaths) based on a large data set of first cousins [21]. Although these two figures are not directly comparable since one refers to an inbreeding effect in a particular family and the other refers to an average effect for a large number of families in different populations they show that the reduction in survival at age 10 for a first cousin progeny with respect to the offspring from unrelated parents detected in the Spanish Habsburg families is very remarkable.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Genética, Facultad de Biología, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain. g.alvarez@usc.es

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus