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HNPCC
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Most common hereditary colon cancer
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Bathesda guidelines and Amsterdam critera provide diagnostic guidelinesfor HNPCC
Not predictive in up to 30% of all cases
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Autosomal dominant
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Mismatch repair
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Highly conserved process fond in prokaryotes and eukaryotes
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Both copies of mismatch-repair gene must be mutated to develop cancer
Can inherit one bad copy then have somatic mutation that affectssecond
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Does not predict cancer perfectly
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Where this mutation occurs dictates where cancer willreside
Mismatch repair gene repairs mismatches
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Error in this leads to accumulations of error
cancer
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Polymorphism
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When a DNA sequence variation causes no significant effect on phenotype
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May influence height and hair color rather than characteristics of medicalimportance
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When identify a variation
must determine whether or not it isdetrimental
Achieved via comparing variations to the Human MutationDatabase
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Marfan Syndrome
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Autosomal dominant
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Majority of mutations in FBN1 gene
Mutation found in 90% of people that meet clinical criterion
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Synonymous differences
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Differences in the nucleotide level that do not translate into differences atthe amino acid level
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Can occur in Marfan’s where genetic testing may show mutation butindividual does not exhibit clinical manifestations consistent w/ disease
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Non-synonymous
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Affect the sequence of the resultant protein
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Likely to result in a change in phenotype or to be associated with a disease
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Hemolytic Anemia
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Fetal HB
2alpha2epsilon
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Adult HB
2apha2beta
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Alpha Thalassemia’s occur when people have mutation in the alpha hemoglobingenes
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