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?
• 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