Midterm 2 - Lecture 1 week 6

Question 1

What is genotyping

Answer 1

Looks at known SNPs in genome and sees which polymorphism person has

Question 2

What are the probes in SNP chips and what are they similar to

Answer 2

DNA complementary to region around SNP
-similar to Illumina flow cell

Question 3

What does a a higher fluorescence mean in SNP probe

Answer 3

More perfect matches have copies bound
-this is the allele person has

Question 4

What kind of fluorescence does heterozygous alleles have

Answer 4

Even fluorescence

Question 5

What kind of fluorescence does homozygous alleles have

Answer 5

Uneven fluorescence

Question 6

True or false: The probe that is brightly fluorescent is the allele that the person has

Answer 6

False
-Person will have the opposite allele that is fluorescent –> because the probe is complementary to person (Watson & Crick base pairing)

Question 7

Why is genotyping problematic?

Answer 7

Does not include all SNPs

Question 8

What are SNP chips

Answer 8

Faster alternative to full genome re-sequencing
-only tests for 600,000 known SNPs

Question 9

What shortcut is used to get around sequencing the whole genotype?

Answer 9

Imputation

Question 10

Haplotype block

Answer 10

Genotypes that tend to get inherited together

Question 11

What is imputation and why is problematic

Answer 11

Inferred SNPs
-based on general patterns of people who have been sequenced
-not representative of everyone

Question 12

Are GWAS inherently biased?

Answer 12

No, but the disproportionate use of tagSNPs from European ancestry haplotype block is

Question 13

How to fix GWAS bias?

Answer 13

-use SNPs from non European ancestry groups
-stop using tagSNPs and use whole genome sequencing

Question 14

Limitations of GWAS

Answer 14

1. TagSNPs used on SNP chips only indicate region of genome –> have to figure out which allele is the causative SNP
2. TagSNPs may not have same inferred SNPs in different ancestry groups
3. SNP chips miss genetic contributors to phenotype