1. Introduction to bioinformatics lecture 11 SNP by Ms.Shumaila Azam

2. Human Genome and SNPs
Now that the human genome is (mostly) sequenced, attention turning to the evaluation of variation
Alterations in DNA involving a single base pair are called single nucleotide polymorphisms, or SNPs
Map of ~1.4 million SNPs
It is estimated that ~60,000 SNPs occur within exons;

3. Goals of SNP Initiatives
Immediate goals:
The hundreds of thousands of SNPs estimated to be present in the human genome
Interest also in other organisms, e.g. potatoes(!)
Establishment of SNP Database(s)

4. Longer term goals: Areas of SNP Application
Gene discovery and mapping
Diagnostics/risk profiling
Response prediction
Gene function identification

5. Polymorphism
Technical definition: most common variant (allele) occurs with less than 99% frequency in the population
Also used as a general term for variation
Many types of DNA polymorphisms, including RFLPs, VNTRs, microsatellites
‘Highly polymorphic’ = many variants

6. Use of Polymorphism in Gene Mapping
1980s – RFLP marker maps
1990s – microsatellite marker maps

7. Gene Discovery and Mapping
Linkage Analysis
Within-family associations between marker
Linkage Disequilibrium (LD)
Across-family associations

8. Crossing over and Recombination

9. Disease-Marker Association
A marker locus is associated with a disease if the distribution of genotypes at the marker locus in disease-affected individuals differs from the distribution in the general population
A specific allele may be positively associated (over-represented in affecteds) or negatively associated (under-represented)

10. Examples: Alzheimer’s
E4 present
E4 absent
Patients 58 33
Controls 16 55
The E4 allele appears to be positively associated with Alzheimer’s disease:
Odds Ratio = (58/16)/(33/55) = 6

11. Linkage Mutation occurs Allele D is created Nearby marker
Allele M was nearby
D and M subsequently transmitted together

12. Candidate Polymorphism Testing
Large SNP collections may allow testing for direct, physiologically relevant associations with trait

13. Diagnostics/Risk Profiling
Identified SNP associations can potentially be used to develop diagnostic tools

14. Response Prediction
Pharmaceutical companies especially interested in this:
Aim to identify those likely to respond
Predict toxicity reactions in susceptible individuals
Response to any kind of substance; creation of ‘functional foods’

15. Gene Function Identification
Alternative to other experimental procedures (e.g. knock-outs, which cannot be used in humans)
Studies to compare individuals with and without naturally occurring disease predisposing genetic profiles