L30 Personal Genomics

Question 1

Personal Genomics is here to stay

Answer 1

• legislation and regulation have not kept pace with technology

Question 2

Reasons for wanting to know more about your genes

Answer 2

• curiosity, personal interest
• lack of access to family medical history e.g. adoptees
• trying to locate lost relatives e.g. adoptees, refugees, victims of trafficking, war

Question 3

Some things you can buy online

Answer 3

see onenote

Question 4

3 main categories of products

Answer 4

1. lifestyle related testing (legal in Australia)
   - how to maximise your athletic performance
   - finding a highly compatible partner
   - what breed is your dog
2. health-related testing (less legal in Australia)
   - what are you at risk of?
   - what lifestyle changes can increase your quality of life?
3. ancestry-related testing (legal in Australia)
   - who are you?
   - what are you related to?
   - where do you come from?

Question 5

DNA romance

Answer 5

see onenote slides

• really non-random mating
• the MHC gene
• HLA gene

Question 6

Personal genomics for your furry friends

Answer 6

see onenote

• to make better decisions for you and your pet
• what breed makes up your dog? So you can understand their behaviour better
• Is your cat lactose intolerance? So you can optimise their diet
• Are they at risk for some genetic disorder? Pretty common in pedigree animals

Question 7

Lifestyle testing ranges from gullible to unsettling

- data

Answer 7

see onenote

• link between data and product can dramatically overstate the strength of their evidence

Question 8

Health testing

Answer 8

more solid but over-promising and under-delivering?

Question 9

Some famous personal genomes

Answer 9

Craig Venter, founder of Celera

James Watson
- requested that all gene info about apolipoprotein E be redacted, citing concerns about the association it has shown with Alzheimer’s disease

Mike Snyder, genomics professor at Stanford
- the “Snyderome”

Question 10

Snyderomics and the fully quantified self

Answer 10

see onenote

• Based on data, Snyder has made lifestyle changes e.g. to lower his changes of becoming diabetic

Question 11

Would you want to know?

- main players

Answer 11

see onenote

• main player health companies are backed by solid science
• 23andme used to offer complex predictions “risk scores” on over 250 conditions but now only offer advice on 9 conditions due to legal problems

Question 12

23andme legal disclaimer

Answer 12

see onenote

Question 13

DIY personalised medicine

Answer 13

see onenote

Promethease
- lets you analyse your genotype against any published association in literature

Question 14

Myriad Genetics

Answer 14

see onenote

• used to own one of your genes
• Myriad patented sequence of the BRCA1 gene in 1994
• their genetic test was the only way women could lawfully access their BRCA sequence
• patents were invalidated in 2013 in the USA, 2015 in Australia so now they own the world’s biggest database on pathogenicity of BRCA1 mutations

Question 15

Over-promising and under-delivering

Answer 15

• Depends on what you expect, these tests cannot capture the true risk of disease, just to genetic predisposition
• genetics is simply one of multiple contributors to disease in most cases, monogenic, highly penetrant disorders are the big exception
• but the uncertainty doesn’t necessarily mean that people don’t have a right to know
• in cases like BRCA, Huntington’s, Alzheimers etc, advance knowledge can be liberating or frightening

Question 16

Can your DNA tell you who you are? What is ancestry?

Answer 16

see onenote

• genetic and genealogical ancestors are not the same
• your first genealogical-but-not-genetic ancestors appear in your pedigree only 8 generations ago = 150 years

Question 17

Everyone has royal ancestors

Answer 17

see onenote

there’s never been enough people for each of us to have separate family trees

Question 18

But maybe you do want more precision

Answer 18

see onenote

• can take results to other companies that combine genetic and genealogical data to fill in your family tree

Question 19

All DTC testing raises issues on multiple fronts

Answer 19

1. ascertainment bias
2. consent, equity, ethics
3. usefulness
4. genetic privacy

Question 20

Biases in SNPs and samples

Answer 20

see onenote

ascertainment bias = your resources such as tag SNP collections are not representative of all extant human diversity

europeans over represented in human genetics
- overestimate european diversity and underestimate non-european diversity

Question 21

Genetic privacy: from HapMap

Answer 21

see onenote

• identifying personal genomes by surname inference

Question 22

Golden state killer caught using relative’s DNA from genealogy websites

Answer 22

see onenote slides

• suspect identified when police created a fake profile using crime-scene DNA and uploaded to GEDmatch
• didn’t find him but ID’d some distant relatives
• GEDmatch contains more data than police databases, which are subject to privacy laws

Question 23

It’s in your DNA

Answer 23

Underlying all these products is the notion of genetic determinism: the idea that your genome dictates everything about you

genetics makes significant contributions to you and your life but so does your environment