Pedigree showing inheritance of hemophilia, an X-linked trait, in the descendants of Queen Victoria. Many of the descendants in the third and fourth generations (third and fourth rows) have been omitted because the mutant gene was not transmitted to them. Offspring whose status is uncertain are indicated with a question mark.

Recent work reveals that the mutation was in the gene for factor 9 (IX) so the disease was hemophilia B. DNA sequencing of samples from the skeletal remains of the murdered Russian royal family reveals that

  • the mutation was a point mutation in the intron preceding exon 4 (of 8) of the factor IX (F9) gene. This splice-site mutation caused a frameshift introducing a premature STOP codon and hence a shortened, nonfunctional, protein.
  • As her carrier status in the pedigree indicates, the DNA of Alexandra contained both the mutant allele and the wild type allele.
  • So did that of one of her 4 daughters (indicated as "4?" in the fourth row and presumably Anastasia).
  • However, the DNA of Czarevitch Alexis contained only the mutant allele, thus accounting for his prior history of severe bleeding.

You can read about this remarkable example of DNA forensics in Rogaev, E. I., et. al., Science, 326:817, 6 November 2009.

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8 March 2011