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MUTATIONS
1. Silent Mutations
 Change in nucleotide has no effect on amino
acid in protein
 Occurs:
 Introns
 Wobble effect
Intron Mutations
 Variable effects
Intron Mutations

m1: Mutations in the promoter region may affect gene transcription may lead to nonfunctional (null) alleles.

m2: Mutations in exons, if they result in the substitution of an amino acid in the active
site or other critical region of the protein, also lead to alleles with modified (reduced)
functionality.

m3: In contrast, exon mutations that result in changes outside the active sites or at 3rd
codon positions may have little or no effect on gene function.
These mutations are called silent (if the amino acid is unchanged) or neutral (if
the change has no effect).

m4: Mutations at critical positions near intron / exon junctions may affect mRNA
splicing and lead to the deletion or retention of entire exons, and result in null alleles.

m5: Mutations that occur in non-coding introns, or

m6: 5' or 3' flanking portions of the gene, may have little or no effect on gene
function. able effects
2. Missense Mutations
 Change in DNA base sequence alters a codon
 A different amino acid is added to protein
 Examples:
 Sickle Cell Anemia
 Hemophilia
Sickle Cell Anemia
 GAA  GUA
 GLU  VAL
Haemophilia
 Sex-linked (X-chromosome) disorder that
impairs blood clotting
 Dominant in males, recessive in females
 Used to stop bleeding when a vessel breaks
 1 in 5,000-10,000
 G A
 GLU  LYS
*Affecting the protein necessary for blood clotting
3. Nonsense Mutations
 Change in DNA base sequence causes a stop
codon to replace a normal codon
 Lethal to cell as protein function is lost
 DEPENDING ON where the stop codon is
 If occurs at beginning of protein sequence  lethal
 If occurs at end of protein sequence  may lose
function
 Example: Thalassemia and DMD
Thalassemia
 Mutation that reduces the rate at which one protein in
hemoglobin (Hb) is synthesized
 Creating incomplete or abnormal Hb  lower function
 AAG  UAG at the 57 codon of the gene
 LYS  STOP
DMD = Duchenne Musclar Dystrophy
 X-linked trait that causes rapid deterioration of
muscles
 Loss of motion, then eventual death
 Affects in 1 in 3500 males
 Females only affected if both parents have allele
 C A G or C A A  U A G or U A A
 GLN  STOP
DMD = Duchenne Musclar Dystrophy
 Dystrophin protein no longer functions properly
 Responsible for connecting muscle fibers to the basal layer
of skin
 Absence of dystrophin permits excess Ca2+ to enter
the cell
 Eventually cell is destroyed from oxidative processes
4. Frameshift Mutations
 Change in DNA base sequence causes the
reading frame of codon to change due to:
 Insertion of base(s)
 Deletion of base(s)
 *INDEL mutations
 Single or double INDEL will cause an amino acid
change
 Triplet INDEL will have milder consequences
 Multiple triplet INDEL can have major effects
 Ex. Fragile X, Cystic Fibrosis
Fragile X
Associated with:
 Martin-Bell Syndrome, the most common form
of inherited predisposition to mental retardation
 Protein FMR1 is not made
 Required for normal neural development
 Characterized by high amounts of CGG triplet
repeats
Fragile X
Cystic Fibrosis
 Recessive disease that causes progressive body wide
disability
 First recognized in the early 1930s
 Scarring of the pancreas
 Early death ~35 years old
 Symptoms (few of the many):
 Difficulty breathing (from lung infections)
 Poor growth
 Diarrhea
 Infertility
 1 in 25 people of European descent
Cystic Fibrosis
 Caused by a mutation in the gene for the protein CFTR
 Regulates sweat, digestion processes, and mucus
 3 base pairs are deleted
 Normal DNA sequence
 T A G A A A  A U G U U U  ILE + PHE
 Mutated DNA sequence
 T A A  A U U  ILE
*ILE is still present but we lose PHE
5. Translocation
 Transfer of a DNA fragment from one site to another
 May get altered function depending on where it was
cut
Ex. Leukemia
Leukemia
 An uncontrolled proliferation of one kind of white
blood cell (leukocyte)
 All descended from a cell that lost ability to maintain cell
cycle
 Translocation between chromosome 9 and 22
 Chromosome 9 is longer than normal
 Chromosome 22 is shorter than normal
6. Inversion
 Chromosomal segment that has reversed its
orientation
 No gain or loss of genetic information
 But gene may be
disrupted
 Protein function
loss