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Flashcards in G15 Deck (22):

what are CDCV

common diseases use to common variants


what are common variants

polymorphisms that occur at 1-5% in populations


what are the two hypotheses for common variants

1. common diseases are due to common variants, several genes contribute, each polymorphism is of small effect - can be detected via association studies
2. common diseases are due to rare alleles of large effect, - cant be detected via association studies


what is the more common correlation between effect size and allele frequency

more likley to get common variants with small effect sizes identified by GWAS
highly penetrant alleles for mendellian disorders are extremely rate with large effect sizes


what is the equation for linkage disequilibrium

D= PABPab - PAbPaB


How do you calculate the coefficient of disequilibirum

r^2 = D^2/ PAPaPBPb


what values can the coefficient of disequilbirum take

range from 0-1
0 = linkage equilibirum
1 = linkage disequilbirum


what do hotspots of recombination produce

blocks of LD in the genome - variation in each block is low


in theory how many SNPs do you need to analyze to determine if LD is complete

only 1 as if LD then should be same


what does local LD result in

SNPs being inherited in haplotype blocks


how are control groups selected in population based case/control studies

age matched
sex matched
ethnicity matched
environment matched
- so differences in marker allele freq in patient population its due to genotypwe


how do you calculate reltative risk of disease

P(disease|exposed to allele) / P(disease| no exposed to allele)
can calculate each using a(a/b) and c/(c+d)
a is case exposed
b is control exposed
c = case unexposed
d = control unexposed


what does RR of 1-1.5 tell you

small effect


what does RR of >2 tell you

large effect


what does a manhattan plot show you

human chromosomes shown, with SNPs associated with disease highlighted.


what does manhattan plot of T2D and FTO fat mass and obesity associated genes show

clusters of SNPs located within first intron associated.
position 16q12
one FTO SNP has high associated with very low P value
The risk allele frequency was at a higher frequency in the case group.


what did FTO studies in transgenic mice show

FTO deletion = lean
FTO dominant missense = lean
FTO over expression = increase fat mass, food intake and body weight
males 10% increase - females more


what did risk allele A of an SNP at rsl9939609 show

associated with increased BMI in eypreans homos = 16% pop are at high risk compared to TT homos
AA = eat more, especially fats


what are the issues with GWAS?

replication between studies isnt good
questionable clinical utility - hasnt got that dfar


what did twn studies show about heritability for obestiy adn what did GWAS findings show

GWAS found 75 vairants for obesity which explains 2-3% of the phenotypic variation - suggests CDCV doesnt hold.


what is an eQTL

genetic loci that affect mRNA expression level of other genes, measured mRNA or protein trait is almost always the product of a single gene with a specific chromosomal location
uses GWAS qtl mappinh approach but maps expression of a particular gene against SNP markers


what did eQTL studies for expression of FTO SNPs show

that SNPs associated with BMI are associated with IRX3 expression not FTO in human brain tissue.