L4 Study Designs Flashcards
What are the 2 purposes of studies
See if it is inheritable/a genetic component eg via twins
See what the association is
Do alleles have to be single bases or snps
No can be sequences of eg cnvs or inversions
How do children of same parents differs so much
Homologous recombination some have different alleles from diff parents
Why is the phenotype and genotype in complex called a probabilistic relationship
Not 100% penetrance
Does having both copies of a risk allele cause you to have disease in complex
No
What is the probability represented as (2 ways)
Odds ratio and genotype relative risk
How to calculate genotype rr
Baseline risk of disease x number of the risk alleles (0-2)
Where are mutations/snps often in complex disease located
Non coding regions therefore affecting gene exp levels more then function
How do you recognise recessive pattern in a pedigree
1 generation usually affected and seen in consanguineous families ie inbreeding
What are family studies used for
Detect a genetic contribution to a disease
What doesn’t family studies do so what do you have to do after
Doesn’t find causal variant so need to do functional tests on model organisms eg via crispr ko or on cell thpes
Do family studies work better for Mendelian disease
Yea
What type of analysis is done on family studies
Segregation analysis
What does this do
Estimates things like gene freq, shared environmental effects, penetrances in the family which best explain the inheritance pattern
Does segregation analysis allow to study polygenic inheritance
Yes to an extent
How is twin studies good for complex to see if there is a genetic determinant
Studies concordance rates between mz and dz since shared environments. If higher concordance in the mz means it is likely genetic factors
What does recurrent risk do
Another way to assess genetic contribution to a disease
What does rr mean
Probability of the disease recurring in family
What does proband mean
The person who first had the disease in the family
Which 3 people related to proband can a recurrence risk be calculated for
Sibling Ks
Offspring Ko
Mz twin Kmz
What is the recurrence ratio
Ks/k (whole popn risk)
If ks is 3 what does this mean
3 fold more likely than rest of popn
Whcih study is done mainly for Mendelian diseases to localise the genetic contributions
Parametric linkage analysis
What does this entail
Using large pedigrees and obtaining dna from then to genotype specific genetic marker loci
What does parametric linkage analysis allow to measure
Co segregation of alleles (in a haplotype)
To see if the allele locus you’re testing is linked to the locus associated with disease
What is the actual hypothesis of linkage analysis
Studying if the locus is linked to a disease locus (not trying to prove it is causing the disease)
Why do you not need to genotype the disease locus in the pedigree in linkage analysis
Can infer patterns eg dominance = Atleast 1 copy , if recessive it means 2 copies and both parents carriers
What is used on complex disorders which is similar
Non parametric linkage analysis
What does this measure
If 2 affected siblings affected for example share genetic material in common from their parents/ancestors
Linkage xant be done on non related people to find variant, so what is done ie using case control
Association studies
Do you always get a direct causal relationship in association studies
No, the allele/ variant you find might just be linked to the causal variant , which is still good as it narrows the genomic region it can be in
What test of correlation is done if an allele is seen in higher freq in cases
X2 test for indep (chi)
Can association studies be done on family pedigrees
Yes you can investigate high risk allele transmission
What type of sequencing/genotyping done on candidate approach
Targeted sequencing or snp genotyping eg sequenom
How has sequencing in gwas developed
Started from micro satellite markers now can use dense microarray snp genotyping up to 5 mill snps
Why is it not useful to sequence whole genome
99% identical
Why does gwas fundings usually have no predictive value in disease
Small odds ratios eg 1.6
