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GENE EXPRESSION and thalassemia mutations.
Write neatly.
2010
1. Examine the 3 mutations in the promoter region of the -globin gene.
a. At what nucleotide base positions are these mutations?
b. Why are these mutations designated with a " – " ?
c. Which promoter mutation is closest to the TATA box?
d. What effect does a promoter mutation have on RNA polymerase?
e. Why do promoter mutations usually result in the mild form (+) of thalassemia (think about
the level of expression of the gene) rather than the severe form (often characterized by a lack
of b-globin protein)?
2. Examine the exons and introns (IVS = intervening sequence = intron) of the globin gene.
How many exons will be spliced together to form the mature mRNA from the pre-mRNA
transcript shown?
3. Find the 4 splice site mutations. Splice sites are where intron is cut and exons ligated.
a. Which 2 splice site mutations occur in the 3’ end of the exon/5’ end of the intron?
b. The normal splice site sequence on the 3' end of the exon is GU. What is the G mutated to in
these 2 mutations?
c. Why would mutation #7 result in an extra long mature mRNA and non-functional protein?
note that the form of thalassemia that results from this mutation is the more severe 0.
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4. A frame shift mutation results from a deletion (or addition) of bases. The reading frame is
shifted. For example: THE COW SAW THE FOX becomes nonsense if the C is deleted:
THE OWS AWT HEF OX. Examine the frame shift mutation #5.
a. In what exon does this frameshift mutation occur?
b. Why does this mutation lead to the severe form of thalassemia (0)?
c. Examine frameshift mutation #6. Which exon contains codon 71 of the gene?
5. Examine mutations #24 and #23. 5’ capping of the mRNA transcript and addition of the 3'
poly A tail are important for mRNA stability. Why would a mutation in either the cap or
poly A tail lead to the + form of thalassemia rather than 0 ?
6. In a nonsense mutation, a nucleotide change results in a codon that specifies a STOP codon
(TAA, TAG, or TGA). Therefore, translation of the messenger RNA will stop prematurely.
Which of the 3 nonsense mutations listed will yield the shortest protein (mutation #)? Note
that abnormally short proteins are referred to as "truncated". Why do the nonsense mutations
lead to the more severe 0 phenotype?
7. Examine the nucleotide change in each of the 3 nonsense mutations. Which nucleotide in the
codon (the first, second, or third) was mutated? Remember, stop codons are either TAA,
TAG, or TGA.
8. Examine the figure for the large deletions detected in 2 patients. Does the person with the 5'
deletion make any  globin protein? What is the basis for your answer? Would you
characterize these patients as 0 or +?
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