Lecture 13: GWAS Flashcards
What is a selective sweep? What could it mean?
Areas where heterozygosity is unusually low. Could mean selection favours this specific allele as all others have been driven out
What is the gene called for the mutation that has left everywhere except Africa? Where is the earlier allele low and frequent?
C21ORF34. Earlier allele is low outside of Africa but makes up the majority of African populations.
What is C21orf34?
Is a linkRNA (large intergenic non-coding RNA) containing 15 exons known to produce at least 19 splice variants
What has c21orf34 been linked to recently?
Leukaemia, attention deficit disorder and risk of obesity in some populations.
How can you find variations that have a phenotypic effect?
you align the sequences of genes from different populations and calculate the timing of divergence between African, European and Asian populations. Can find the genes with accelerated evolution as everyone is still under pressure so is evolving. Can find how many changes have occurred in each population eg the lactose gene underwent a selective sweep.
What are association studies and what is the strategy?
They aim to uncover the genetic basis of certain disease or phenotypic trait. They genotype a large number of individuals exhibiting variation in the trait of interest and use statistical analysis to find associations between genotypes at particular loci and the phenotype of interest.
How many variable sites have been identified from sequencing the human genome?
6 million
What do the probes do?
Probes are printed using microarray technology. the higher the fluorescence, the more frequent the base pair and scan the entire genome.
What does log(p) need to be for significance?
Very high
What was the first GWAS study on, how many cases and controls were there and how many SNPs were assessed?
Complement factor H role in macular degeneration. 96 cases, 50 controls and over 116,000 SNPs assessed.
What was found?
SNP in CFH gene confers 7.4 fold increase likelihood of AMD. Several other genes were found to have a role in macular degeneration
What is very rare?
That you find an SNP that makes you 100% likely to have something
What gene is associated with chondrolysplasia in dogs?
FgF4 gene
How was the chondrolysplasia example carried out?
Sequenced short and long legged dogs at as many different sites as possible.
How is regression shown?
Plot the phenotype vs the genotype with both alleles. have to use a much smaller p value for significance
