Problem 1
• Mutation in noncoding sequence change
the number of protein molecules produce,
but, generally each protein molecule made
will have a normal amino acid sequence.
Give an example of a mutation that agrees
with the rule. Give examples of some
exceptions to this rule, and describe how
the alteration in the amino acid sequence
are generated.
Problem 8 Chapter 11 text
Answer Problem 1
• Give an example of a mutation that agrees with the rule.
– many simple beta-thalassemia with transciption mutations
– fragile X syndrome
• Give examples of some exceptions to this rule, and
describe how the alteration in the amino acid sequence
are generated.
– exceptions to this rule can arise, for example, from splice site
mutations that lead to missplicing of an exon. The exon may be
excluded from the mRNA, generating either an in-frame deletion
of the protein sequence or causing a change in the reading
frame, leading to the inclusion of different amino acids in the
protein sequence
Problem 2
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Sickle cells anemia was one of the first diseases for
which a unique molecular marker was discovered.
Sickle-cell Anemia is due to a single-nucleotide
substitution (A T) in the second position of the sixth
codon of the beta-globin gene that is responsible for
the difference between the standard A and sicklecell S alleles. The sequence of the standard A allele
(CCTGAGG) happends to correspond to an MstII
restriction site (CCTNAGG) that is not present in
the S allele (CCTGTGG). The beta-globin gene
region includes two flanking MstII sites (red lines).
a. For allele A how many bands will total DNA from
the individual tested produce when cut with MstII
b. For allele S how many bands will total DNA from
the individual tested produce with cut with MstII
c. Indicate the geneotype for each individual
d. Indicate individual who have the sickle cell trait
e. Which child has the highest fitness rating in a
malaria ridden area in Africa
5’
GTG
bs globin gene
3’
Region recognized by probe
5’
GTG
normal bA globin gene
3’
Region recognized by probe
Answer Problem 2
•
a. For allele A how many bands will total DNA from the
individual tested produce when cut with MstII
•
b. For allele S how many bands will total DNA from the
individual tested produce with cut with MstII
•
Total DNA from the individual tested is cut with MstII: a probe
specific for the region including the nucleotide substitution will
then produce two bands if the standard A allele is present,
and one band if the sickle-cell S allele is present; a
heterozygote (sickle-cell trait) will therefore show three
bands.
c. Indicate the geneotype for each individual
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two bands
one band
allele A two small bands
allele S one large band
d. Indicate individual who have the sickle cell trait
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–
people who have the trait are heterozygous. Heterozygous
individuals will have three bands
Individuals I-1,1-2,II-3
•
e. Which child has the highest fitness rating in a malaria ridden
area in Africa
•
Note this test depends on the coincidence that the nucleotide
substitution responsible for sickle-cell happens to occur in
such a way as to create an RFLP: the MstII site itself has
nothing to do with sickle-cell anemia.
–
individual II-3 heterozygous survive malaria better
Problem 3
The figure below shows a PCR bases micro-array hybridization assay of the DMD exons. In the
figure below PCR-fragments containing DMD exons are spotted in triplicate on each array (top left
exons 1-24, top right exons 25-48, bottom left exons 49-72, bottom right exons 73-79). Top: signal
obtained with control DNA (Cy-5 labeled). Bottom: signal obtained with DNA from a patient (Cy-3
labeled). Does this patient have DMD. If they do what exons are deleted
Answer Problem 3
Does this patient have DMD. Yes . If they do what exons are deleted. The assay suggests they
are missing exon 3-20
control
missing 3-20