Download - NCPP 2 Hekman
12/10/2019
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The Genomics of the American Mutt
How genes affect appearance
and behavior in mixed‐breed dogs
Jessica Hekman, DVM, PhD
Broad Institute
of MIT and Harvard
How can we safely place
shelter dogs
with unknown history
and unknown genetics?
SightSpeed
Retrieving
Herding
Herding
Retrieving
Guarding
Guarding0
50
100
150
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Answer
coun
t
retrieves objects (e.g., balls, toys, sticks): strongly agree - strongly disagree
Labs and Retrieving Interest
Retrievers like to retrieve…mostly
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Retrieving is heritable…mostly
MuttMix: A project to collect guesses about
mixed‐breed ancestry
MuttMix
A project
to…
• 31 mutts
• At least 3 breeds
• Guess top 3
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MuttMix.org: What we found
Some dogs had 19+ breeds!Number of breeds doesn’t correlate with correct answer
432,743 questions answered
25% accuracy overallProfessionals: 28% accuracy
Could we genetically test for behavior?
ATGCCGATCGTTDog #1ATGCCAATCGTT
Single Nucleotide Polymorphisms (SNPs)
Dog #2
one letter difference
Most SNPs don’t DO anythingUseful markers for tracing ancestry
correlated
“Is this SNP correlated with my trait?”
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Coat Color in Boxers
~2% deaf
Solid Flash White
S S swS sw sw
10 dogs9 dogs 1 dog
Find region with most correlated SNPs
position in dog genome
difference
over gene MITF
Karlsson et al, Nature 2008
makes protein needed for pigment cell migration
hypothesis:
regulation of M
is disrupted
Karlsson et al, Nature 2008
White coat & Deafnessboxers and bull terriers
Karlsson et al, Nat Genetics
Cone‐rod dystrophydachshunds
Wiik et al, Genome Research
Ridge & neural tube defectRhodesian ridgebacks
Salmon‐H. et al, Nat. Genetics
ALSfive breeds
Awano et al, PNAS
Ectodermal dysplasiahairless breeds
Drögemüller et al, Science
Osteoimperfectadachshunds
Drögemüller et al, PLOS Genet
single gene “Mendelian” traits
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Compulsive disorder in dogs
Movies by Alice Moon‐Fanelli
normal behavior done too much
distressing, time‐consuming and impairing
onset in adolescence
poor response to treatment (including SSRIs)
highly heritablechromosome
1 gene: CDH2
Dodman et al, Molecular psychiatry 2010
Compare genomes of 92 affected and 67 healthy dobermans
Function of CDH2
• Neural cadherin
• Found in glutamatergic synapses
• Synaptic plasticity (learning and memory)
cadherin
noCCD
noCCD
CCD
Unaffected Unaffected Affected
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10% chancethey had CCD
25% chancethey had CCD
60% chancethey had CCD
Darwin’s Ark: the genetics of dog behavior
Example question Citizen science dog genetics = more DNA samples
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June 201819,044 dogs2,198,453 answers4000+ DNA samples
Darwin’s Dogs includes all dogs
Breeder
ShelterRescue
Other
Morphological traits Behavioral traits
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Does it work?
We can predict height – pretty well!
Does it work? Does it work?
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Thank you to the organizations, owners, and dogs!darwinsark.org
Acknowledgements
IAABC
Marjie Alonso
Adria Karlsson
Many, many others
@UMass
Kathryn Lord
Brittney Logan
Shirley Xue Li
Gaurav Chauhan
Kathleen Morrill
@BroadElinor KarlssonMichele KoltookianJeremy JohnsonRoss Swofford
Diane Genereux
Jacob Alonso
Get in touch:[email protected]
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