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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

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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  

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