Scientists estimate that every one of us has 510 potentially deadly mutations in our genes

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Scientists estimate that every one of us has 5-10
potentially deadly mutations in our genes
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What are mutations? How do we get them?
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Allele 1 gt functional protein Allele 2 gt
abbreviated, nonfunctional protein
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Scenario 1 UGG (Trp) gt UAG (STOP)
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Allele 1 gt functional protein Allele 2 gt
abbreviated, nonfunctional protein Scenario 2
X introduces a different amino acid Allele
1 gt functional protein Allele 2 gt depends!
Will it affect the proteins structure or
activity?
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Scenario 2 UGG (Trp) gt UCG (Ser)
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Allele 1 gt functional protein Allele 2 gt
abbreviated, nonfunctional protein Scenario 2
X introduces a different amino acid Allele
1 gt functional protein Allele 2 gt depends!
Will it affect the proteins structure or
activity? conservative vs. nonconservative
substitutions
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(No Transcript)
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Allele 1 gt functional protein Allele 2 gt
abbreviated, nonfunctional protein Scenario 2
X introduces a different amino acid Allele
1 gt functional protein Allele 2 gt depends!
Will it affect the proteins structure or
activity? Scenario 3?
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Scenario 3 GCU (Ala) gt
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Any other DNA changes you can think of that
could affect genes?
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Scenario 2 X introduces a different
amino acid Scenario 3 X does not change the
amino acid Scenario 4 -X or X causes a
frameshift Scenario 5 X could cause a
splicing error which causes a frameshift any
others?
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Mutation, polymorphism, or variant? mutation
allele with pathogenic variation variant an
allele with 1 frequency in population,
sequence change has no effect on fitness
neutral polymorphism a variant allele with
1 frequency in population, sequence change has
no effect on fitness neutral
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Alleles are variant forms of a gene
Scenario 1 X introduces a stop codon
Scenario 2 X introduces a different
amino acid Scenario 3 X does not change the
amino acid Scenario 4 -X or X causes a
frameshift Scenario 5 X could cause a
splicing error which causes a frameshift
What type of change would you expect to be the
most common and the cause of most diseases?
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Summary of statistics for pathogenic mutations in
1163 genes Type of mutation Percentage Base
substitution 75 amino acid substitution
52 stop codon generated 11 stop codon
eliminated lt1 splice site mutation 11 regu
latory 1 Small deletion 18 Small
insertion 7 Data from Human Gene Mutation
Database, Table 3.2 Human Evolutionary Genetics
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• Huntingtons Disease
• dominant progressive disorder of the nervous
  system that usually appears in adults 35-45 years
  old
• symptoms include involuntary movements, loss of
  motor control, and decline in cognitive abilities
• mutant alleles of HD gene contain 36 CAG
  repeats, compared to 26 in normal alleles