Personalized Medicine

Question 1

Personzliaed genomics/ personalized medicine

Answer 1

• predict dx predisposition and treatment response
• explain traits and where they come from
• identify relatives
• identify ancestry
• participate in citizen science research
• usually based on genotyping (from saliva or blood) but newer tests based on sequencing available in humans
• great promise but ethical concerns

Question 2

almost never come across common variants with

Answer 2

large disease effect because they would be weeded out unless its a dx that doesn’t have a big impact on fitness

Question 3

what type of variants do we test for

Answer 3

high effect because its the most useful (these will usually be rare but will have high effect)

Question 4

hardest things to identify by genetic means

Answer 4

rare variants of small effect

Question 5

if find common dx variant will have __ effect

Answer 5

low

Question 6

Huntington’s

Answer 6

this is a rare dx with large effect, it is autosomal dominant but occurs after age or reproduction; can’t treat it if you know you’re getting it

Question 7

Alzheimner’s dx

Answer 7

diff genes can make you signigicalty more likely to get alzheimers not too much to do but maybe some mediations you can give to try to slow down progression; do you tell people if they’re prone to it is big ethical question if there isn’t anything you can do

Question 8

Pharmocogenomics

Answer 8

study of how genetics affects an individuals response to drugs

Question 9

MDR1

Answer 9

multidrug resistent gene in dogs; 1 copy bad 2 is worse affects ability to metabolize common drugs; pump to pump toxic drugs out of cells is not functioning properly in these dogs which makes doses ok in normal dogs toxic; affects ivermectin, anticancer, antidiarrheal drugs; doses that are approved for dogs by FDA are within level that is ok for dogs with 2 copies MDR1; collies V affected by this; have to be carful not to use bulk drugs split by weight, treat for sarcastic mange without MDR1 test, or use garlic with these dogs

Question 10

ALT and genetics

Answer 10

mutation on chromosome 13 affects ALT levels in dogs; heterozygous are in normal reference range with each homozygous on either side of it; effects where values land if dog is in liver failure this is important to be aware of

Question 11

importance of companies like 23 and me

Answer 11

have 10s of millions of people in their database which is more than you can get for research studies
- have Died genes for freckles, photic sneeze reflex, asparagus anosmia, asthma risk factors, Parkinson’s and other important dis, also associations for educational attainment, age of recproduciton ect

Question 12

mitochondria genome

Answer 12

does not recombine only passed down matrilineally

Question 13

animal genome testing

Answer 13

have over 200 known key mutations in dogs for large mendilian traits; difference btwn embark and wisdom panel is number of markers used

Question 14

wisdom pannel and optimal selection

Answer 14

baed on power density arrays (~2000 markers) suitable for overall ancestry estimation (and for optimal selection) trait and dx mutation testing

• doing research stuff so need dense arrays for GWAS
• low density array less expensive than high density array

Question 15

embark pannel

Answer 15

based on high density array (~200,000 markers) suitable for local ancestry estimation, trait and dx mutation testing, linkage testing for updated results, and genetic mapping
- high density array more expensive than low density array

Question 16

what can these tests tell you

Answer 16

• can tell you level of wolfiness (based on selective sweeps btwn dogs and wolves)
• predicted adult weight
• genetic age (if you give dog age it can give you genetic age based on aging on small dogs relative to big dogs, this is NOT based on DNA sequence change with aging because that isn’t a thing)
• get summary of dis you can test for risk for and carrier for
• can also find out what parts of chromosomes consistent with what breeds (embark)
• can get genetics behind coat color varriation
• inbreeding coefficient (embark catches these; useful to breeders)
• can find dog family nearby

Question 17

Inbreeding info

Answer 17

look at graph of pedigree coefficient of inbreeding vs genetic inbreeding coefficient and see what the level actually is

Question 18

dog matchmaking

Answer 18

there are sites that allow you to look for dogs that are clear for certain traits or at risk of certain traits and you can decide who to breed to based on this also looks at inbreeding coefficient and theorizes potential offspring and their expected colors

Question 19

merele coat pattener

Answer 19

looked at associations and found chromosome 18 position had high association; don’t know if this is causal variant or just a related variant so can email owners and check and see if those dogs also have blue eyes and find that
GWAS SNP is related but duplication is far more related so duplication is probably causal variant (not every dog with it has blue eyes but the vast majority do)

Question 20

Ethical considerations of genetic testing

Answer 20

• how much certainly should be required in genetic results
• should we only test for actionable diseases
• who owns the data you or the company doing the sequecing
• what should be done with incidental findings (ie someone gets test to figure out metabolic issues but have genes for macular degeneration do you tell them especially if there is something they can do about it)
• where to we draw line regarding prenatal testing? If a fetus has gene for Huntington’s do you abort? What about alzheimers?
• what about 3rd parties (close relatives genes are tied into yours what if they don’t want the info out there, tribe/ can (some tribes don’t believe in genetic testing but what if one member does, insurance (can’t discriminate based on genetic status if you’re an insurance company its illegal in people not in dogs)

Question 21

advantages of personalized medicine in companion animals vs humans

Answer 21

• fewer ethical concerns with testing (dog doesn’t care who dad is)
• less regulatory burden (but this means can get some bad tests too)
• tests can be more predictive for complexx traits (bc simpler genetic architecture for many traits)
• many breeds more distinguishable than human popluatoins
• inbreeding greater impact in many animal breeds
• companion animals servie as great translational model

Question 22

companion animals as model for translational research

Answer 22

• cats and dogs more genetically similar to humans than mice
• more similar in size, longevity, and envionment
• genes and sometimes mutations often identical
• quality vet care (similar diagnoses and treatments)

Question 23

Doberman narcolepsy

Answer 23

genomic sequencing in dobermans lead to finding genes in people that caused this that previously hadn’t been known to be a narcoleptic varriant

Question 24

Duchenne’s muscular dystrophy in goldens

Answer 24

humans and dogs have same mutation in same gene; have population of dogs who they breed who have this; one golden had this but didn’t display signs nor did his puppies because of compensatory mutation in Jagged1

Question 25

possible disadvantages of personalized medicine in companion animals

Answer 25

• breeders and breed clubs have huge influence on standers and breed preferences if they misunderstand genetic results can lead to subpar decision making and issues for the breed down the road
• differences btwn breeds so test that are predictive in one breed may not be predictive in another
• lack of regulatory overbite means genetic testing quality in companion animals v dependent on quality of lab/company

Question 26

comprehensive genetic screen doesn’t mean animal is

Answer 26

free of genetic defects because can’t test all of the genetic dxs bc dnt know variants for all of them