L4 Study Designs

Question 1

What are the 2 purposes of studies

Answer 1

See if it is inheritable/a genetic component eg via twins

See what the association is

Question 2

Do alleles have to be single bases or snps

Answer 2

No can be sequences of eg cnvs or inversions

Question 3

How do children of same parents differs so much

Answer 3

Homologous recombination some have different alleles from diff parents

Question 4

Why is the phenotype and genotype in complex called a probabilistic relationship

Answer 4

Not 100% penetrance

Question 5

Does having both copies of a risk allele cause you to have disease in complex

Answer 5

No

Question 6

What is the probability represented as (2 ways)

Answer 6

Odds ratio and genotype relative risk

Question 7

How to calculate genotype rr

Answer 7

Baseline risk of disease x number of the risk alleles (0-2)

Question 8

Where are mutations/snps often in complex disease located

Answer 8

Non coding regions therefore affecting gene exp levels more then function

Question 9

How do you recognise recessive pattern in a pedigree

Answer 9

1 generation usually affected and seen in consanguineous families ie inbreeding

Question 10

What are family studies used for

Answer 10

Detect a genetic contribution to a disease

Question 11

What doesn’t family studies do so what do you have to do after

Answer 11

Doesn’t find causal variant so need to do functional tests on model organisms eg via crispr ko or on cell thpes

Question 12

Do family studies work better for Mendelian disease

Answer 12

Yea

Question 13

What type of analysis is done on family studies

Answer 13

Segregation analysis

Question 14

What does this do

Answer 14

Estimates things like gene freq, shared environmental effects, penetrances in the family which best explain the inheritance pattern

Question 15

Does segregation analysis allow to study polygenic inheritance

Answer 15

Yes to an extent

Question 16

How is twin studies good for complex to see if there is a genetic determinant

Answer 16

Studies concordance rates between mz and dz since shared environments. If higher concordance in the mz means it is likely genetic factors

Question 17

What does recurrent risk do

Answer 17

Another way to assess genetic contribution to a disease

Question 18

What does rr mean

Answer 18

Probability of the disease recurring in family

Question 19

What does proband mean

Answer 19

The person who first had the disease in the family

Question 20

Which 3 people related to proband can a recurrence risk be calculated for

Answer 20

Sibling Ks
Offspring Ko
Mz twin Kmz

Question 21

What is the recurrence ratio

Answer 21

Ks/k (whole popn risk)

Question 22

If ks is 3 what does this mean

Answer 22

3 fold more likely than rest of popn

Question 23

Whcih study is done mainly for Mendelian diseases to localise the genetic contributions

Answer 23

Parametric linkage analysis

Question 24

What does this entail

Answer 24

Using large pedigrees and obtaining dna from then to genotype specific genetic marker loci

Question 25

What does parametric linkage analysis allow to measure

Answer 25

Co segregation of alleles (in a haplotype)

To see if the allele locus you’re testing is linked to the locus associated with disease

Question 26

What is the actual hypothesis of linkage analysis

Answer 26

Studying if the locus is linked to a disease locus (not trying to prove it is causing the disease)

Question 27

Why do you not need to genotype the disease locus in the pedigree in linkage analysis

Answer 27

Can infer patterns eg dominance = Atleast 1 copy , if recessive it means 2 copies and both parents carriers

Question 28

What is used on complex disorders which is similar

Answer 28

Non parametric linkage analysis

Question 29

What does this measure

Answer 29

If 2 affected siblings affected for example share genetic material in common from their parents/ancestors

Question 30

Linkage xant be done on non related people to find variant, so what is done ie using case control

Answer 30

Association studies

Question 31

Do you always get a direct causal relationship in association studies

Answer 31

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

Question 32

What test of correlation is done if an allele is seen in higher freq in cases

Answer 32

X2 test for indep (chi)

Question 33

Can association studies be done on family pedigrees

Answer 33

Yes you can investigate high risk allele transmission

Question 34

What type of sequencing/genotyping done on candidate approach

Answer 34

Targeted sequencing or snp genotyping eg sequenom

Question 35

How has sequencing in gwas developed

Answer 35

Started from micro satellite markers now can use dense microarray snp genotyping up to 5 mill snps

Question 36

Why is it not useful to sequence whole genome

Answer 36

99% identical

Question 37

Why does gwas fundings usually have no predictive value in disease

Answer 37

Small odds ratios eg 1.6