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