Clinical Applications of Molecular Biology II

Question 1

What are the advantages of NGS?

Answer 1

1. Throughput and cost → can resequence human genomes for thousands of dollars
2. Very high-quality consensus reads

Question 2

What are the disadvantages of NGS?

Answer 2

1. Short reads
2. Limites specificity for repeat and duplicated regions
3. Limited ability to run de novo assembly
4. Difficult sequences
5. Throughput - sometimes only want to test one site

Question 3

What is the name of the governing body w/ guidelines to report mutations?

Answer 3

Human Genome Variant Society

Question 4

CFTR:c.1652G>A, p.Gly551Asp. What is CFTR?

Answer 4

Gene

Question 5

CFTR:c.1652G>A, p.Gly551Asp. What is c?

Answer 5

Coding

Question 6

CFTR:c.1652G>A, p.Gly551Asp. What is 1652G?

Answer 6

nt#

Question 7

CFTR:c.1652G>A, p.Gly551Asp. What is A?

Answer 7

Change

Question 8

CFTR:c.1652G>A, p.Gly551Asp. What is p?

Answer 8

Protein

Question 9

CFTR:c.1652G>A, p.Gly551Asp. What is Gly?

Answer 9

Original aa

Question 10

CFTR:c.1652G>A, p.Gly551Asp. What is 551?

Answer 10

aa#

Question 11

CFTR:c.1652G>A, p.Gly551Asp. What is Asp?

Answer 11

New aa

Question 12

What is the difference between incidental and secondary findings?

Answer 12

Incidental = genetic variant(s) that are located IN genes that have been associated with the PRIMARY INDICATION FOR TESTING, but the impact of the variant is unrelated to the primary indivation for testing

Secondary = genetic variants(s) that are located in genes OTHER THAN those that have been associated with the PRIMARY INDICATION FOR TESTING and may have an impact on health of patient and family members

Question 13

How do you classify variants based on evidence of pathogenicity?

Answer 13

Very strong
→ PVS1 - null variant

Strong
→ PS1 - same aa change as a previously established pathogenic variant regardless of nucleotide change
→ PS2 - de novo
→ PS3 - well-established in vitro or in vivo study support damaging effect on gene or gene product
→ PS4 - prevalence of variant in affected individuals is significantly increased compared w/ the prevalence in controls

Moderate
→ PM1
→ PM2
→ PM3
→ PM4
→ PM5
→ PM6

Supporting
→ PP1
→ PP2
→ PP3
→ PP4
→ PP5

Question 14

How do you classify variants based on evidence of benign impact?

Answer 14

Stand Alone
→ BA1

Strong
→ BS1
→ BS2
→ BS3
→ BS4

Supporting
→ BP1
→ BP2
→ BP3
→ BP4
→ BP5
→ BP6
→ BP7