BIOS E-1a Lecture 14 112111 annotated

BIOS E-1a Lecture 14 112111 annotated - Lecture 14 DNA and...

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Lecture 14: DNA and the Biology of Cancer Reading: Chapters 7, 8, 9 1
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2 Mutation • A heritable change in the genetic material • Essential to the continuity of life – Source of variation for natural selection • New mutations are more likely to be harmful than beneficial • DNA repair systems repair DNA damage • Cancer is a disease caused by gene mutations
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3 Gene mutations alter the DNA sequence Point mutation affects only a single base pair 2 basic alterations 1. Change base sequence 2. Add or remove nucleotide(s)
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4 Examples • Change base sequence – Base substitution • Add or remove a single base pair 5’ – CCCGCTAGATA – 3’ 5’ – CCCGC G AGATA – 3’ 3’ – GGGCGATCTAT – 5’ 3’ – GGGCG C TCTAT – 5’ 5’ – GGCGCTAGATC – 3’ 5’ – GGC A GCTAGATC – 3’ 3’ – CCGCGATCTAG – 5’ 3’ – CCG T CGATCTAG – 5’
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5 Gene mutations may affect amino acid sequences • Silent mutation – Does not alter the amino acid sequence – Genetic code is degenerate • Missense mutation – Changes a single amino acid in a polypeptide – May not alter function if substituted amino acid is similar in chemistry to original – Sickle-cell disease is the result of a single amino acid substitution
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6 Point mutation leading to sickle cell anemia
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7 • Nonsense mutation – Change from a normal codon to a stop or termination codon – Produces a truncated polypeptide • Frameshift mutation – Addition or deletion of nucleotides that are not multiples of 3 – Completely different amino acid sequence downstream from mutation
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8 Point mutations within the coding sequence of genes
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Gene mutations outside of coding sequences • A mutation may alter the sequence within a promoter and affect the rate of transcription – May enhance or inhibit • Mutations may occur in regulatory elements or operator sites – Mutation may later DNA sequence of operator so that repressor protein does not bind 9
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Effects of mutations outside the coding sequence of a gene 10
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11 Germline or somatic cell mutations • Exact time and location of a mutation is critical to severity of effect and to the ability to pass on the mutation • Germline cells give rise to gametes – Can occur in a sperm or egg cell or in cell that gives rise to eggs and sperm • Somatic cells are all other body cells – Can occur early or late in development • Genetic mosaic results from patches of mutated tissue
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12 Differences between germline and somatic mutations
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13 Spontaneous or induced mutations • Spontaneous mutations result from abnormalities in biological processes • Rates vary from species to species and from gene to gene • Expected rate of background mutation approximately 1 mutation for every 1 million genes
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14 Some common causes of gene mutations
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15 • Induced mutations are brought on by environmental agents • Mutation rate higher than spontaneous mutation rate • Mutagens are chemical or physical agents – Can alter DNA in various ways
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16 Examples of mutagens
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BIOS E-1a Lecture 14 112111 annotated - Lecture 14 DNA and...

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