Human Heredity 11th Edition by Michael Cummings

Exercise 13

Hemophilia and History
Hemophilia, an X-linked recessive disorder, is characterized by defects in the mechanism of blood clotting. This form of hemophilia, called hemophilia A, occurs with a frequency of 1 in 10,000 males. Because only homozygous recessive females can have hemophilia, the frequency in females is much lower-on the order of 1 in 100 million.
Pedigree analysis indicates that Queen Victoria of England carried this gene. Because she passed the mutant allele on to several of her children, it is likely that the mutation occurred in an X chromosome she received from one of her parents. Although this mutation spread through the royal houses of Europe, the present royal family of England is free of hemophilia because it is descended from Edward VII, an unaffected son of Victoria.
Perhaps the most important case of hemophilia among Victoria's offspring involved the royal family of Russia. Victoria's granddaughter Alix, a carrier, married Czar Nicholas II of Russia. She gave birth to four daughters and then a son, Alexis, who had hemophilia. Frustrated by the failure of the medical community to cure Alexis, the royal couple turned to a series of spiritualists, including the monk Rasputin. While under Rasputin's care, Alexis recovered from several episodes of bleeding, and Rasputin became a powerful adviser to the royal family. Some historians have argued that the czar's preoccupation with Alexis's health and the resulting insidious influence of Rasputin contributed to the revolution that overthrew the throne. Other historians point out that Nicholas II was a weak czar and that revolution was inevitable, but it is nonetheless interesting to note that a mutation carried by an English queen had a considerable influence on twentieth-century Russian history.
Which members of the pedigree could have been carriers, and which might have been the source of the mutation?