• HNPCC

o Most common hereditary colon cancer

o Bathesda guidelines and Amsterdam critera provide diagnostic guidelines
for HNPCC
 Not predictive in up to 30% of all cases
o Autosomal dominant
• Mismatch repair
o Highly conserved process fond in prokaryotes and eukaryotes
o Both copies of mismatch-repair gene must be mutated to develop cancer
 Can inherit one bad copy then have somatic mutation that affects
second
• Does not predict cancer perfectly
• Where this mutation occurs dictates where cancer will
reside
 Mismatch repair gene repairs mismatches
• Error in this leads to accumulations of errorcancer
• Polymorphism
o When a DNA sequence variation causes no significant effect on phenotype
o May influence height and hair color rather than characteristics of medical
importance
o When identify a variationmust determine whether or not it is
detrimental
 Achieved via comparing variations to the Human Mutation
Database
• Marfan Syndrome
o Autosomal dominant
o Majority of mutations in FBN1 gene
 Mutation found in 90% of people that meet clinical criterion
• Synonymous differences
o Differences in the nucleotide level that do not translate into differences at
the amino acid level
o Can occur in Marfan’s where genetic testing may show mutation but
individual does not exhibit clinical manifestations consistent w/ disease
• Non-synonymous
o Affect the sequence of the resultant protein
o Likely to result in a change in phenotype or to be associated with a disease
• Hemolytic Anemia
o Fetal HB
 2alpha2epsilon
o Adult HB
 2apha2beta
• Alpha Thalassemia’s occur when people have mutation in the alpha hemoglobin
genes
  Silent carrier state-don’t see effect
 Hemoglobin H disease-lack of fxn alpha protein is great enough to
cause anemia and serious health problems
 Alpha thatlassemia major
• No fxn alpha genes exist
• Beta Thalassemia
o Caused by mutation affecting the production of beta globin proteins
o Found in people with mediteranean descent
o Major form results in anemia
• Sickle Cell Anemia
o Mutation of the B-globin gene
o Codes for HbS which is an aggregating form of HB
o Glutamatevaline substitution
• Sickle beta thalassemia
o Inherit both beta thalassemia and sickle hemoglobin s mutation
o Have reduced amounts of beta protein as well as abnormal s hemoglobin
• Point Mutation
o Cause 95% of b thalassemia’s and 5% of alpha thalassemias
• Persistent fetal HB + sickle cell disease=no symptoms