Transcript Single Nucleotide Polymorphism

Single Nucleotide Polymorphism
Mining SNP Data
What is a SNP?
• Mutation of a single nucleotide (A,C,T,G)
• Some can be associated with various
phenotypic differences
– Drug resistance
– Propensity towards disease
• Over 5 Million SNP locations identified in
the human genome, growing daily
How can SNPs aid research?
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Biomarkers
Association Studies
Genotyping
Loss of Heterozygosity
DNA Copy Number
SNP Microarray Chip
• Use microarray
platform similar to
gene expression
studies
• Hybridization of
fluorescently tagged
samples to probes
which correspond to
sequences of interest
Affymetrix Probe Layout
• Two alleles, A and B
• PerfectMatch (Signal)
MisMatch
(Background)
• Sense (forward)
Antisense (reverse)
• Shifted Sequences
(-2, -1, 0, 1, 2)
• Read intensity values
Genotyping
• Each probe gives some indication of allele
A or B
• Aggregate information from all probes for a
given SNP
• Create classifier for each SNP
• Make genotype calls
– (AA, BB, AB, AB_A, AB_B, Unknown)
SNPs and Cancer
• Tumors frequently exhibit DNA alterations
– Loss (0 or 1 copy)
– Additions (3 or more copies)
• Could be responsible for some cancers
– Tumor suppresor genes
– Oncogenes
Loss of Heterozygosity (LOH)
• Each cell contains two copies of a given chromosome
(mother’s and father’s)
• Loss of Heterozygosity occurs when there is a change in
relative allele signals (AB in normal and AA in tumor, for
instance).
DNA Copy Number Changes
• Determine regions where additions or losses take place.
• Complimentary to LOH studies
– LOH can detect “balanced” mutations
– Copy number analysis can detect amplifications or losses of
homozygous markers
Other Analysis
• Association Studies
• Haplotypes
• Shared LOH regions