The Future of Genomic Medicine

Question 1

what do we not know about DNA?

Answer 1

• what all of the DNA in the human genome codes for?
• causes of some rare monogenic conditions
• genetic variants that influence risk of complex diseases and drug responses
• how genetic and environmental factors interact

Question 2

what are the principles of how pharmacogenomics works?

Answer 2

• studying the genetic basis for the differences between patient responses to drugs
• enzymes from the liver catalyse drugs, enzymes are proteins coded for by genes

Question 3

how to get the dose of 6-mercaptopurine correct using pharmacogenomics?

Answer 3

• some people metabolise the drug more quickly or slower than other people
• the ones who metabolise it more slowly have more side effects so need a smaller dose
• people who respond fast have two copies of TPMT
• people who metabolise the drug slowly are heterogeneous for a mutation in the gene
• the small proportion of the population who are homozygous for the mutations will not metabolise the drug

Question 4

how to get the type of drug right with MODY and type 1 diabetes ?

Answer 4

• MODY- mature onset diabetes of the young
• single gene disorder
• MODY can be treated with an oral drug
• some patients with MODY are misdiagnosed to hype T1D
• they could have oral drugs instead of injections
• you need genetics to check this

Question 5

what does the genome wide association studies look at?

Answer 5

• each person has 3 million SNPs

- the different variants can be compared using genome wide association studies

Question 6

how can genetic tests aid monogenic diseases?

Answer 6

• Can provide carrier status information
• Can predict risk of late-onset disease
• Essential to provide GENETIC COUNSELLING - some of the information may be very sensitive

Question 7

how can genetic tests aid complex diseases?

Answer 7

• Limited clinical utility
• causes undue alarm
• offers false reassurance
• there are some data privacy concerns

Question 8

what are applications of whole genome sequencing?

Answer 8

• Identify new gene mutations in monogenic disease

- Identify the differences between normal cells and cancer cells - therefore uses targeted treatment

Question 9

how did DNA sequencing identify mutations responsible for miller syndrome?

Answer 9

DHODH gene

• Multiple malformation syndrome
• Characteristic facial features - includes ‘cupped’ ears
• no toes

Question 10

how did DNA sequencing identify mutations responsible for SCHINZEL-GIEDION SYNDROME?

Answer 10

• SETBP1 gene
• Severe mental retardation
• Multiple congenital abnormalities
• Life-limiting

Question 11

practical issues of genetic information in healthcare

Answer 11

• Huge amount of information - expensive and time-consuming

- Difficult to decide which information is clinically relevant

Question 12

ethical issues of genetic information in healthcare

Answer 12

-Protection of data

Question 13

ethical issues of PGD?

Answer 13

• Involves discarding unused embryos
• Disability rights arguments
• designer babies
• eugenics

Question 14

what is allowed to use PGD?

Answer 14

o Severe early onset genetic disease e.g. Tay Sachs
o Severe late onset genetic disease e.g. Huntingdon’s Disease
Disease with incomplete penetrance
o To choose tissue-matched baby than can provide umbilical cord blood to treat sick sibling

Question 15

limitations of PGD?

Answer 15

• IVF- physically and emotionally draining

- Only suitable for diseases where the genetic/chromosomal abnormality is known