C785 Mutations

10. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', which DNA sequence would represent a nonsense mutation?

5' GTC GCA TAG TGA 3' Correct! 5' GTC GCA TAG TGA 3'. A point mutation (single nucleotide change in a codon) that changed the G in the second position of the third codon (TGG) into an A (TAG) changed the amino acid tryptophan (Trp) into a premature stop codon - a nonsense mutation. See Figure 1-19 in the Module 1 text for more information.

26. True or false: Silent mutations are point mutations that result in no change in amino acid sequence True

Correct! A single nucleotide change in a codon (point mutation) which does not change the amino acid sequence is a silent mutation. See Figure 1-19 in the Module 1 text for more information.

Learning Objective

Given two varying DNA sequences, the student will identify mutation types (e.g., silent, insertion, frame shift, deletion). (2 questions on the assessment)

12. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', what kind of mutation would create the mutant gene sequence 5' ATC GCA TGG TGA 3'?

Missense mutation A missense mutation arises from a point mutation which causes the amino acid coded for to change. See Figure 1-19 in the Module 1 text for more information

22. The normal sequence of a section of the HLA-B27 gene, a genetic marker of the inflammatory disease Ankylosing spondylitis, is 5'- CGG CAG AAU UUA -3'. A mutation results in the following mRNA sequence: 5'- CAG CAG AAU UUA -3'. This is an example of a(n)

Missense mutation CGG in the first codon of the normal gene is mutated to CAG, changing an Arg codon into a Gln codon. A change in a codon that also changes one amino acid in the protein is a missense mutation. See Figure 1-19 in the Module 1 test for more information.

24. A specific kind of mutation in the opsin gene related to color blindness causes a premature termination of the translation process. This results in a shorter opsin protein than usual. What *specific* type of mutation could have caused this?

Nonsense mutation This is a nonsense mutation, a kind of point mutation that changes a single base pair in a codon to a STOP codon resulting in termination of translation. This results in a protein that is shorter than it is supposed to be (truncated). See Figure 1-19 in the Module 1 text for more information

6. When comparing a normal and mutant gene sequence, how do you identify a frameshift mutation?

The number of nucleotides between the normal and mutant gene sequences is different and the amino acid sequence is different. Background. Errors that increase or decrease the number of nucleotides in a gene cause frameshift mutations. The insertion of an extra base or the removal of one of the bases will change which groups of three bases that the ribosome reads when it translates the message. This is said to 'shift' the 'reading frame' from the correct groups of three bases to different groups of three. To visualize what a frameshift is, imagine you are given a string of letters and told to start at the beginning and read every group of three letters: CATDOGRATPIGAPE. You would get "cat dog rat pig ape". But if we add an extra letter, say CATDFOGRATPIGAPE, following our "read every group of three" rule, we would get "cat dfo gra tpi gap e". Shifting our 'reading frame' by adding one more letter completely changes what we read. This is similar to what happens with a frameshift mutation. . See Figure 1-19 in the Module 1 text for more information.

28. True or false: Nonsense mutations are point mutations that change a single base in a codon to a stop codon that terminates translation.

True A single nucleotide change in a codon (point mutation) introduces a premature stop codon into an amino acid sequence is a nonsense mutation.

14. Which of the following would be considered a point mutation to a DNA strand that consists of a nucleotide sequence: 5' CTG ACG TAT CTT AAT 3'

a. 5' CTG ACG TAA CTT AAT 3' Correct! A point mutation changes a single nucleotide in a codon, in this case, changing the T in the third position of the third codon to an a (TAT > TAA).

5. Frameshift mutations

change the number of nucleotides in a mutant gene compared to the normal gene. Examples are insertion and deletion mutations. frameshift is, imagine you are given a string of letters and told to start at the beginning and read every group of three letters: CATDOGRATPIGAPE. You would get "cat dog rat pig ape". But if we add an extra letter, say CATDFOGRATPIGAPE, following our "read every group of three" rule, we would get "cat dfo gra tpi gap e". Shifting our 'reading frame' by adding one more letter completely changes what we read. This is similar to what happens with a frameshift mutation.

27. True or false: Missense mutations are insertions or deletions of one or more base pairs (if the number of base pairs is not a multiple of 3) that disrupt the coding of a protein.

false. A single nucleotide change in a codon (point mutation) which changes the amino acid sequence is a missense mutation. If additional base(s) are added to the sequence, that is an insertion mutation in the DNA.

8. A mutation that results in a mutant gene with more nucleotides compared to the normal gene is a ________________ mutation

insertion Correct! Adding more nucleotides is known as an insertion Background. An insertion mutation adds nucleotides to a gene and is a type of frameshift mutation, which changes the way the mRNA codons are read, changing the amino acid sequence. See Figure 1-19 in the Module 1 text for more information.

9. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', which DNA sequence would represent a deletion mutation?

5' GTC GCA TGT GA 3' A deletion mutation removed a G from the third codon (TGG). Then, the first T from the 4th codon becomes the third base of the third codon, 'shifting' the reading frame. This is a deletion mutation in the DNA. Notice that there are now fewer nucleotides in the mutant gene compared to the normal gene. See Figure 1-19 in the Module 1 text for more information.

13. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', which DNA sequence would represent a deletion mutation?

5' GTC GCA TGT GA 3' A deletion mutation removed a G from the third codon (TGG). Then, the first T from the 4th codon becomes the third base of the third codon, 'shifting' the reading frame. This is a deletion mutation in the DNA. Notice that there are now fewer nucleotides in the mutant gene compared to the normal gene. See Figure 1-19 in the Module 1 text for more information.

25. The mutation that causes color blindness by making the gene for the opsin protein encode a shorter opsin protein could have resulted from a malfunction of __________.

DNA polymerase The correct answer is DNA polymerase. This enzyme could have added an erroneous nucleotide, and its proofreading activity could have missed it. While this type of event is rare, DNA polymerase is known to make a mistake that it doesn't correct about one in one hundred million!

29. True or false: Frameshift mutations are point mutations that change a single base pair in a codon such that the codon now encodes a different amino acid.

This statement is false. Frameshift mutations insert or delete nucleotides from a gene, changing the way mRNA codons are read, changing the amino acid sequence of a protein.

16. The mRNA sequence 5'-CUC AUA GCC UGA CCC-3' is mutated to 5'-CUC UAG CCU GAC CC-3' What peptide chain is formed by the mutated sequence?

Leu The correct answer is Leu. A deletion mutation deleted the first A in the second codon (AUA), resulting in a frameshift that now reads the second codon as a STOP codon. Stop codons are not part of the amino acid sequence, so the protein would only have one amino acid (CUC codes for Leucine (Leu)).

6. A deletion mutation

might cause a nonsense mutation. Deletion mutations always change an amino acid sequence by either removing amino acid(s) from the protein or changing the way codons are read, changing the entire amino acid sequence past the mutation. This mutation could cause the regular stop codon to be split between two adjacent codons, allowing translation to occur beyond the stop codon in the normal gene. Alternatively, the change in "reading frame" could introduce a premature stop codon.

10. Which of the following would be considered a point mutation to a DNA strand that consists of a nucleotide sequence: 5' CTG ACG TAT CTT AAT 3'

5' CTG ACG TAA CTT AAT 3' A point mutation changes a single nucleotide in a codon, in this case, changing the T in the third position of the third codon to an a (TAT > TAA).

12. The following is the mRNA sequence for actin, a protein that provides structure to a cell: 5' ACU AGA CGU UUU UAA 3'. A mutation to the actin gene results in the production of the following mRNA: 5' ACU AGA CAU UUU UAA 3' What type of mutation is this?

Missense CGU in the normal gene is mutated to CAU, changing the amino acid from arginine (Arg) to histidine (His). A change in a codon that also changes one amino acid in the protein is a missense mutation. See Figure 1-19 in the Module 1 test for more information.

7. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', what kind of mutation would create the mutant gene sequence 5' GTC GAC ATG GTG A 3'?

Insertion mutation An insertion mutation adds nucleotides to a gene and is a type of frameshift mutation, which changes the way the mRNA codons are read, changing the amino acid sequence. See Figure 1-19 in the Module 1 text for more information.

3. Point mutations

change a single nucleotide in a mutant gene compared to the normal gene. Examples are missense, nonsense, and silent mutations. A single nucleotide change in the DNA is a point mutation. For example, changing an A for a C would be a point mutation. Point mutations do not increase or decrease the number of nucleotides in a gene, and they might (missense and nonsense mutations) or might not (silent mutations) change the amino acid sequence of the protein. See Figure 1-19 in the Module 1 text for more information.

5. Frameshift mutations

change the number of nucleotides in a mutant gene compared to the normal gene. Examples are insertion and deletion mutations. To visualize what a frameshift is, imagine you are given a string of letters and told to start at the beginning and read every group of three letters: CATDOGRATPIGAPE. You would get "cat dog rat pig ape". But if we add an extra letter, say CATDFOGRATPIGAPE, following our "read every group of three" rule, we would get "cat dfo gra tpi gap e". Shifting our 'reading frame' by adding one more letter completely changes what we read. This is similar to what happens with a frameshift mutation.

4. A missense mutation

changes a single amino acid in a protein. A single nucleotide change in the DNA (point mutation ) that changes a codon in the mRNA such that it codes for a different amino acid that it did before is called a missense mutation. The missense mutation changes one amino acid in the amino acid sequence of a protein. For example, changing the codon UUU (codes for Phe) to UUA (codes for Leu) is a missense mutation. This See Figure 1-19 in the Module 1 text for more information.

11. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', which DNA sequence would represent a silent mutation?

5' GCG TGG TGA 3' A silent mutation (single nucleotide change in codon, no change in amino acid sequence) would arise by changing the A in the second codon to a G, (GCA > GCG), both of which represent adding alanine (Ala) into the protein. See Figure 1-19 in the Module 1 text for more information

8. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', which DNA sequence would represent a nonsense mutation?

5' GTC GCA TAG TGA 3' 5' GTC GCA TAG TGA 3'. A point mutation (single nucleotide change in a codon) that changed the G in the second position of the third codon (TGG) into an A (TAG) changed the amino acid tryptophan (Trp) into a premature stop codon - a nonsense mutation. See Figure 1-19 in the Module 1 text for more information.

19. The normal sequence of a section of the HLA-B27 mRNA, a genetic marker of the inflammatory disease Ankylosing spondylitis, is 5'- CGG CAG AAU UUA -3'. Which mutant mRNA represents a silent mutation?

5'- CGG CAG AAC UUA -3' A silent mutation (single nucleotide change in codon, no change in amino acid sequence) could arise by changing the A in the second codon to a G, (AAU > AAC), one asparagine (Asn) codon is changed into another Asn codon. The protein still has an Asn where it is supposed to have an Asn. See Figure 1-19 in the Module 1 text for more information.

21. The normal sequence of a section of the HLA-B27 gene, a genetic marker of the inflammatory disease Ankylosing spondylitis, is 5'- CGG CAG AAU UUA -3'. Which mutant mRNA represents a deletion mutation?

5'- CGG CAG AAU UA -3' A deletion mutation removed a U from the last codon (UUA). Notice that there are now fewer nucleotides in the mutant gene compared to the normal gene. See Figure 1-19 in the Module 1 text for more information.

23. The normal sequence of a section of the HLA-B27 gene, a genetic marker of the inflammatory disease Ankylosing spondylitis, is 5'- CGG CAG AAU UUA -3'. Which mutant mRNA represents a nonsense mutation?

5'- CGG UAG AAU UUA-3' The correct answer is 5'- CGG UAG AAU UUA-3'. Changing the C in the second codon (CAG) to a U changed the codon from CAG > UAG, changing the amino acid glutamine (Gln) into a premature stop codon - a nonsense mutation. See Figure 1-19 in the Module 1 text for more information.

9. If the coding (non-template) DNA sequence of a normal gene is 5' GTC GCA TGG TGA 3', what kind of mutation would create the mutant gene sequence 5' GTC GAC ATG GTG A 3'?

Insertion mutation An insertion mutation adds nucleotides to a gene and is a type of frameshift mutation, which changes the way the mRNA codons are read, changing the amino acid sequence. See Figure 1-19 in the Module 1 text for more information.

18. The following is the mRNA sequence for actin, a protein that provides structure to a cell: 5' ACU AGA CGU UUU UAA 3'. A mutation to the actin gene results in the production of the following mRNA: 5' ACU AGA CAU UUU UAA 3' What type of mutation is this?

Missense CGU in the normal gene is mutated to CAU, changing the amino acid from arginine (Arg) to histidine (His). A change in a codon that also changes one amino acid in the protein is a missense mutation. See Figure 1-19 in the Module 1 test for more information.

17. In sickle cell anemia, the DNA coding strand is mutated from GAG to GTG. This results in an amino acid change from Glutamic Acid to Valine. Which of the following terms correctly describes this mutation? (check all that apply)

Missense mutation Point mutation "missense and point mutation describes this mutation. GAG in the normal gene is mutated to GTG in sickle cell anemia, changing the amino acid from valine (Val) to glutamate (Glu). A single nucleotide change in a codon (point mutation) that also changes one amino acid in the protein is a missense mutation. See Figures 1-19 and 1-20 in the Module 1 text for more information.

11. The RNA sequence 5'-CUC AUA GCC UGA CCC-3' is mutated to 5'-CUC AUA GCC UAA CCC-3' What kind of mutation is this?

Silent in the second position of the third codon is mutated to a G, changing the codon from UAA to UGA. This changes one STOP codon into another STOP codon, so there is a STOP codon where there should be a STOP codon. This is not a premature STOP codon. Since the amino acid sequence doesn't change, this a silent mutation. See Figure 1-19 in the Module 1 text for more information.

2. A nonsense mutation

changes a codon to introduce a premature stop codon. A nonsense mutation occurs when a point mutation (change in single nucleotide) changes a codon to a STOP codon- which causes the protein synthesis to prematurely terminate. For example, UGC (codes for Cys) changed to UGA (STOP) would cause the protein synthesis to stop early resulting in a truncated protein (non functional)

1. A mutation in the DNA that changes the sequence of a codon but does NOT change the amino acid sequence of the protein describes a _____ _____.

silent mutation.