Finding Diseases

Question 1

• OR calculation?
• PAR calculation?
• OR and PAR in genetic studies? ex?
• In general, how are diseases located?
• What is used? (3)
• 1? Used for?
• 2? What must be considered? (2) Random?
• 3? Individual vs. population? Must consider?
• Table comparing approaches: x axis? y axis?

Answer 1

• Risk of disease with gene variant/ not having disease with variant
• Decrease in incidence if risk factor were eliminated
• Not always the same; genetic risk could have very low OR and high PAR
• Positional cloning using polymorphic DNA markers; Microsatelites, SNP’s, CNV’s
• Forensics
• Ethnic differences and haplotypes context (blocks with SNP’s that are not purely random with recombination)
• Individually rare but collective common; ethnicity as well)
• Effect (OR); Frequency (Rare to common)

Question 2

• Hypothesis driven approaches:
• 1? May be ID-ed via? Sometimes good for? Accuracy? Where on chart?
• 2? Where on chart? Typical design? % accuracy? 2 major flaws?

Answer 2

1.) Candidate Gene Sequencing: GWAS; Mendellian disorders; bad; moderate/high effect size but rare

2. ) Candidate gene association studies: Common risk alleles with small/mod effect size; case/control; 96% false positives
3. ) Doesn’t include data from other studies
4. ) Many confounders that are tough to control for

Question 3

• Hypothesis free approaches:
• 3? Where on chart? How do they test genes? Performed how? Useful for? Calculation used? With haplotypes? 2 Disadvantages?
• 4? Where on chart? How many SNP’s used? In order to be valid? Plot used? Traits tested for? Disadvantages? (2)
• Combined approach used?
• A good way to find diseased genes in men. inheritance?

Answer 3

3. ) Big effect size but rare; indirectly; test families; mendellian inheritance; LOD= likelihood of data if loci linked / likelihood if loci unlinked; can follow them; expensive and need multiplex family
4. ) Common with low/mod effect size; thousands; need independent replication; manhattan; complex traits; expensive and need verification

• Find candidate genes and then GWAS
• Exome sequencing among related affected parties