FINAL EXAM: TAKEHOME

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FINAL EXAM TAKE-HOME

• Assessment of Significance in Cancer Gene SNPs

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AIM

• By using SNP information in Cancer Genome Anatomy
  Project SNP500Cancer Database learn to read SNP
  data, analyze allelic and genotypic frequencies,
  test whether different populations differ in
  their allele frequencies from each other and
  evaluate your findings and propose a case/control
  study for a cancer SNP.

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ATM
http//snp500cancer.nci.nih.gov/
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Compare Cancer500 and HDP
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Test If Two Sources of SNP info Differ
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Test whether subpopulations are different?
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Compare Caucasian vs. Afr. American
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Compare Caucasian vs. Hispanic
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Test whether a population genotypic frequency is
in HWE
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HWE X2 TESTS
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HWE Tests
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HWE
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Hispanics
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HWE Tests
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TAKE-HOME EXAM

• INTRODUCTION Provide background information
  about your gene of interest based on literature.
  Make sure you cite 2 or more articles.
• RESULT 1 Create a table with the following
  information
• a table that summarizes the allele frequencies
  (minor allele freq vs. major allele freq. for the
  total population considered) for about 8 or more
  SNPs. In this table make sure that you also
  indicate the genotypic frequencies and whether
  they are in HWE (test, and report a X2 and
  p-value).

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TAKE-HOME EXAM

• RESULT 2a Answer the following question Do
  non-synonymous SNPs generally have lower
  frequencies when compared to synonymous and/or
  intronic or regulatory region SNPs? Explain based
  on your findings, and discuss why or why not
  would that be so.
• RESULT 2b Select a nonsynonymous SNP from your
  table and locate this SNP on the cDNA sequence.
• What might be the implications of this amino acid
  change (e.g., does it correspond to a specific
  domain?).
• Is this specific nucleotide highly conserved
  across different organisms (e.g., among mouse,
  rat, and humans). Align sequences from three
  different organisms find this specific amino acid
  change due to SNP, and assess how conserved this
  amino acid is when compared to the rest of the
  sequence.

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TAKE-HOME EXAM

• RESULTS 3 Investigate a few SNPs (nonsynonymous,
  synonymous, and/or regulatory) from your table
  and answer the following question
• Are there any SNPs that differ in allele counts
  across different populations?
• Test two SNPs (for each SNP, perform fishers
  exact test between two pairs of populations
  e.g., caucasian vs. hispanic, caucasian vs.
  african american). Evaluate your results and
  discuss why different populations may have
  different allele frequencies based on
  evolutionary and functional perspectives, and
  specifically for your gene of interest.

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TAKE-HOME EXAM

• FUTURE PERSPECTIVES Design an experiment
  (including selection of the case and control
  populations, molecular methods that you will use,
  and how to interpret the results) to study this
  SNP to find out whether it could be involved in
  initiation or progression of a specific type of
  cancer.