The Hapsburg dynasty ruled Spain from 1516 to 1700, reigning over the height of the Spanish empire. The dynasty ended when the last king, Charles II, who suffered physical and mental disabilities, died without issue despite two marriages. Inbreeding had been thought to play a role in the family's extinction.
A group of biologists from Spain developed an extended pedigree of more than 3,000 individuals over 16 generations so that they could calculate the "inbreeding coefficient" of the Spanish Hapsburg kings. The inbreeding coefficient is a measure of relatedness between two individuals. Here's an example:
Take a first-cousin mating. First cousins share a set of grandparents. For any particular gene in the male, the chance that his female first cousin inherited the same gene from the same source is 1/8. Further, for any gene the man passes to his child, the chance is 1/8 that the woman has the same gene and ½ that she transmits that gene to the child so 1/8 X ½ = 1/16. Thus, a first-cousin marriage has a coefficient of inbreeding F =1/16 .
The six kings of Spain married a total of 11 times. Nine of the marriages were "consanguineous unions in a degree of third cousins or closer." There were even two uncle-niece unions (eww). Over time, the biologists calculated, the inbreeding coefficient rose from 0.025 for Philip I, the founder of the dynasty, to 0.254 for Charles II. His inbreeding coefficient--0.254--is as high as that expected from a parent-child or a brother-sister relationship (double eww).
In addition to the high inbreeding coefficients, the biologists cited two other lines of evidence that inbreeding was the cause of the Spanish Hapsburgs' demise: First, the family experienced a high rate of infant mortality, with half of the children failing to reach age one (compared with 80 percent survival at that time in Spanish villages). Second, many of Charles II's disabilities and illnesses--short stature, weakness, intestinal problems, sporadic hematuria, impotence/infertility--could be explained by two genetic disorders, combined pituitary hormone deficiency and distal renal tubular acidosis. The probability that an individual would inherit two recessive traits would be extremely low, but inbreeding made that much more likely.
This wouldn't seem to have much relevance here in the present, except as an interesting side story in the history books. However, the authors note that consanguineous marriages account for 20 to 50 percent of all unions in certain populations in Asia and Africa and reach as high as 77.1 percent among army families in Pakistan. In those families, more than 60 percent of marriages are between first cousins.