1. Silent Mutations Change in nucleotide has no effect on amino acid in protein Occurs: Introns ...
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Transcript of 1. Silent Mutations Change in nucleotide has no effect on amino acid in protein Occurs: Introns ...
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 non-functional (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