B2.013 Genomic Medicine in Primary Care

Question 1

what is a SNP array analysis?

Answer 1

sparse sequencing
determines nucleotide at 600-1000k spots
0.03% of genome sequenced

Question 2

what is a single nucleotide polymorphism?

Answer 2

one nucleotide change between two sequences

Question 3

how many SNPs determine an ApoE variant?

Answer 3

2

Question 4

are SNPs usually a direct determinant of disease?

Answer 4

no

Question 5

which enzyme is associated with codeine conversion to morphine?

Answer 5

cyp2D6

Question 6

what are 3 types of codeine metabolism pathways?

Answer 6

major: codeine to codeine-6-glucuronide
secondary: codeine to norcodeine
minor: codeine to morphine

Question 7

what is an n-of-1 trial?

Answer 7

treat patients and determine if a treatment is effective on a one to one basis, instead of overprescribing

Question 8

what is trio exome sequencing?

Answer 8

patient + both parents

Question 9

what is an exome?

Answer 9

protein coding part of the genome (1%)

Question 10

how do you sequence an exome?

Answer 10

1. purify genomic DNA from blood
2. amplify protein coding regions
3. high throughput sequencing
4. computational variant analysis
5. clinical correlation

Question 11

what does de novo mean?

Answer 11

the mutation is new in the patient (not inherited)

Question 12

how does high throughput sequencing work?

Answer 12

sequence fragments by creating fluorescent markers for each nucleotide base, look at pattern of fluorescence at each location on the gene

Question 13

what are sequences compared against?

Answer 13

human genome project templates

Question 14

how many variants exist in a genome?

Answer 14

3 million

Question 15

how many variants in an exome?

Answer 15

15-20k

Question 16

what are two filters for ignoring variants?

Answer 16

remove non-synonymous SNPSs (don’t change amino acid)

remove previously known variants (occur frequently in population, probs not the source of the disease)

Question 17

what is the N-terminal?

Answer 17

the beginning of a sequence

Question 18

what is the C-terminal?

Answer 18

the end of a sequence

Question 19

what is a conserved amino acid?

Answer 19

common between protein homologs

Question 20

what is an amino acid with specificity?

Answer 20

not conserved among all homologs, but conserved within subgroups

Question 21

what are 4 major exome sequencing limitations?

Answer 21

short reads
data interpretation
protein function does not equal organism function
other factors beyond protein coding region can influence outcome