Bioinformatics 4: Genetic variation and health Flashcards
Number of nucleotides involved in the main classified types of genetic variation at different scales? Associated mutation types?
single nucleotide substitutions/insertions/deletions (INDELS) : RFLPs / SNPs
STR repeat number variation : 4-10 nucleotides (Microsatellites) - VNTRs
STR repeat number variation 2: 10-60 nucleotides (Minisatellites) - still VNTRs
Transposon: indels, inversions, duplications 100s-1000s nucleotides
Structural Variants: indels, invesions, duplications 10-100s kilobases
Cytologically visible (FISH) variants: indels, inversions, duplications, translocations: >1 Mb
What is the definition of a SNP?
Single Nucleotide Polymorphism
-> any single nucleotide variation from the ‘normal’ sequence
“allele”
Main features of SNPs
- main changes
- abundance
- how do they occur?
approx 2/3 are T:C (or A:G depending on strand) change
Average abundance 1/1000bp
~ 2 per gene (exons)
~ 1 aa change per gene
occur due to replication errors/mutations
What was the purpose of the SeattleSNPs project? Result?
Was focused on indentifying, genotyping, and modelling associations between SNPs in candidate genes and pathways the underlie inflammatory response
Result: very successful SNP discovery approach (~40000 SNPs discovered)
The two stages in SNP genetyping?
Allele discrimination - distinguish between 2 nucleotides
Allele detection - presence or absence / two state
Methods of allele discrimination?
Hybridisation-based: (ASO / Microarrays)
Extension based: (ASPCR / SBE)
Ligation based: (MLPA)
Cleavage based: (Invader assay)
Methods of allele detection?
Mass based (electrophoresis / mass spectrometry
Fluorescent signal based (illumina)
Chemiluminescence based (Pyrosequencing)
Definition of haplotype?
A haplotype is a group of alleles in an organism that are inherited together
What was the purpose of the HapMap project?
Finding, discovering and tagging haplotype associated SNPs to create a haplotype map based on geographic location
