FINAL EXAM: TAKE-HOME

Assessment of Significance in Cancer Gene SNPs

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.

ATMhttp://snp500cancer.nci.nih.gov/

Compare Cancer500 and HDP

Test If Two Sources of SNP info Differ

Test whether subpopulations are different?

Compare Caucasian vs. Afr. American

Compare Caucasian vs. Hispanic

Test whether a population genotypic frequency is in HWE

HWE X2 TESTS

HWE Tests

HWE

Hispanics

HWE Tests

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).

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.

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 fisher’s 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.

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.