Question

5. Consider the wild-type F8 gene. What would happen to the 1) transcript

(mRNA) sequence and quantity, 2) to the protein (sequence, quantity, function) and 3) the person’s

overall phenotype if they were homozygous (both copies of the gene are the same) for a 3 base-pair

deletion in the:

i. First intron

ii. First exon

iii. The promoter

iv. 5’UTR

v. Last exon

6. What environmental factor could affect the phenotype caused by an F8 null mutation?

Thrombophilia is a medical condition characterized by an increased tendency to form blood clots

(thrombosis). Like hemophilia, thrombophilia can be genetically inherited. In 2009, Simioni and

colleagues1 described two brothers who had episodes of thrombosis at a very young age. DNA

analysis revealed that both of them had inherited a mutant F9 allele from their mother (F9*).

7. How does the thrombophilia phenotype compare to the hemophilia phenotype?

8. Recall information at the start of the problem set about two genes, F8 and F9. What kind of mutation in

the F9 gene could result in thrombophilia? Propose a mutation type and where it would be located

within the gene, and a brief explanation (2-3 sentences max)

9. Could mutations in the F8 gene also cause thrombophilia? Explain (1-2 sentences)

10. What do you think would happen (consider clotting phenotype) if a male carried both a null F8

hemophilia-causing allele (F8–), such as the one presented above, and a F9* thrombosis-causing allele

on his X chromosome? You may want to consult the clotting pathway

(http://www.ncbi.nlm.nih.gov/books/NBK22589/?rendertype=figure&id=A1401) and recall that F8 is also

called VIIIa and F9 is also called IX (inactive form) and IXa (active form).

Answer 1

Q5.