Transcript FINAL EXAM: TAKE-HOME

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.
http://snp500cancer.nci.nih.gov/
ATM
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 nonsynonymous 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.