Cheek to Cheek:
Genetic Discoveries
and You
Stephanie A. Santorico, Ph.D.
Professor
Department of Mathematical & Statistical Sciences
Human Medical Genetics and Genomics Program
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Data Revolution
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~ 4
00
~ 1
3
~ 1
00,0
00
~ 5
00,0
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~ 2
,500
0,00
0
~ 3
,200
,000
,000
=
4
3,200,000,0006
7
3 meters
per CELL
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2.0 × 1013 meters or
70 trips to the
sun and back
IDENTICALD
I
F
F
E
R
E
N
T
Humans are 99.9% genetically identical
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“We are more alike, my friends, than we are unalike.”
― Maya Angelou
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Alleles = A and G
GENE
G
G
My genotype = GG at location
20,000
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AGCGGGACCAGCCTGGGGCAGGAGACACCCACTGACTCGCACACCGCCTAATTCAGCCCGCGAAACCGAGTCAGCCCTAATTCCCCCGGCCCTGCACCCAACCAGGAGGCCAGCTAGGGCCCGGCGCCCAGCTGCGCGAGTCAAAGGCACCTCGAA
GCCTACACGTCCTCACGAGCCACGGGCTCCAGGGCAGCGCCGACCCGCACGTTGCGCCGAAACTAACCACGCGGCACGGTGCATCGCGCTTAATCGCCCCCCCCGCGCCTCCCAAACGGCGCATCGGCGTACAGAGGCGACTAGCGGTGGGTCAGC
CGGGCCCCCGAACGCCACCCCTGAAACGGCAGCAGGTAAACGCAAAGCCAACGGTCCCCGGTCTCGGCATAACGCCACACGTCGTCTTCTTCAAAGGGCAAAACCTAGCAGACTATCAGTCACTCAGCGAATTGGCCCCTCGGCCTGGCGAGAGAAC
GGGCACAGGAGGTGGCGATACTTACACAAACACCGACAACACACGAACGTACCGCGAACCCCGCAAGTAACCGACCGCATCAGAGCGCGGGTGGACCCACCACCTGCACAGCACAGCCCACAACTGCGCCGGGGTGTCCGGGAGAGCCCACCACGC
CAACAACCAGCCCACGCAAGTGACAGCCTCGCGGGAGACCCCTGACACGACGGAGTATACGGCGAAGCCAAAGTCCCCGACCCAGCCCTCAAGCGCTTCACCACGCATCACGGCATGCCACTAAGCATAACACTCTTCTGCAGCTGACACACCAGGC
GCAAGCTTCGACCCGCCAGCCACAGCGACATACCGTAGCGAACCTCCCGCCCAGCAACTACGTCAACCCCCACCACGCCGGATTGAAAGCCACACGAACCGTATACAACTTCACACATTATACAAAACAACAACCAGCAGCCATCACCCTCTGAGCCC
CAGGCCCAGCGGGAAGATTTAACCAGCCCAATAAAGTACCATAGCAGCCCACCTAACCGCACAGAAATGCAACAATACATCCAGCACTGTTCAGAGTCACCTCCCTTAGCGAGTGTCACCAGAACAACGGAACCAACGAACGCAGGGCCACTTACCAC
CGACAGGACCGGCAGGTCTAACAGGGTAACGTGACCTACCCACTCCTAATCCCGACAAACACACCACCTCACTAACATGGCGTCCGGAGGGGCACAACGAGCAAATAGACCCACCAAGGATACACAGGTACGACGAACAGGATTGATAACAGACCGC
GTGATAAATATGACCAAGCAAGCAAACCAGGACCCGGATTCCGCCGCACTACCATCGGCCGGGGGTCTTTAGACGTAGCACAGGCACCGAAGAAACCGGCCCCCAGGGCCGACACCACCCCCACGACCCCATTGTGTTCCGCTGGGTGATAAACGTT
AGCTTAGTGTCCGCATGCGCCATGGCTGGCAACACCCACGTCAGAGCAGAGTCGAAGTCCAGCCAACAACACGGAAACGATGACAAAAACATAACACCAGCATCCCCGTCCGGACCCCTCGCGACCCAAAGGCAGAAATACACCACGGCACCCCAAC
CGGCGAAGCTCCTCCACCCCCCTTAACCCTATATCAGCCTAGAAAAGCACTGCTGGCAAAGTCAGCCTTAAACCCATCGATTCAGCCCAACATCCCCTCAGCAGACGTAGCGCCCAAGCAAGACGAAAAGCTCAGGCCTTGAGATGCCAATCCTGTAC
AGAGCGACGCGCCTGCGCCGACCGCGCGCCGCGACAAGGCCCACGCCGACCTAACTATACCCAATIGACGGACDGAATAIGTGACGCCGGGACCCCAACACCCGCTGACCCCACAGACAAAACAAATAAGTAAGGACCACGCAACGCAGACCGGAGC
TATGACTCAAAAATCAAAGACGGTACACCCTCCATCTTAGCCGCCCACAATCAACCAACCTCGCCACACGAATCGACCGCAAAGAAGTCCCCCACTCCCTGCCTCGTCCCAAACGGACACCCCCGGGCACCGAACCTCACATCGCCGATAGCAAACGG
CACAGGGTTGCCACATCCGTTATCACTACGCTACCAACAACCAGAAAGGATGGCCGCGCGTAATACGCAAAATTCAATGTGCGTAGAGCATGGACTCCCCGCATACTGCCTAATACCAGCAAAGGGGACCGGCGACTTGCAGAGTCATGACCAGGTTA
ACAGACGTCCGTGTATCCTCATCCACATCAGAAGTCTACTGCTACGGCGTTGCTACCGCAACCGCGAGTCTCGGAGATTGAAAGGTTTCAGACCCAAAGCCTACGTGGGCCGAAACGAACAACCGAGCACAATGTCAAGTACCCAGGGGCGAAATTTC
CGGAGCCAAAGGCAGCAGTGTGGCGGAGCACGCGCACGTACATAACGAAACAACGCCTGACAATCACAGGCCAGGCCCACAGGAGTGACAGCATTAGCGAGCCACCGACAAGGATAATGGAAATTCCGAGGACGAAGTGGGAGGGCAACAACGCGC
CAAGGCCTTGCAGCGCGCCGAGCTCTCAATAGTTCGCGCCTCGCCCGATCCACGGTAAAGATACGCAGGGCAGGTCGCGGCCCCATGCCGTCGCTAGTGAATGGATTAACGCAACTTAGCGCACACCCATTCGTCACCACCAGTCGCCCTACGGGCC
GGCTCCTCTTCTGCAGGATCGCGCGACAGCCGACGAAAAGGAACACCTAAACCCAATCGGGCACAAGACCGACGAGTCGTACTCCCTAACCAACTACCGGCAGTTATCGGCTAAATTCCCTAACCACGCGTAGCAATGACGCCTGCGCCAACTGAAAC
CGCCAGCGCCCGCGCATGTTGCTATGCACGACTCATCCGAACAAGAGGAACCATGCGAGAGGTACACACCACCGCCCCCGAAACCCCGAAGGCACGGCATTGGCAAGAGGAATTTAGGAGGATCGTGCTAGCCCCGCGTGAAGTTACAGACGACAGA
CGCCAACGCAAAAACAGATCCGACATAACAGCAAAATGTAGGTCAACCAAAGTAGGATACGGCCGGACTTGGGCTAGGTTAACGCCAATGCAGCAAAGAAGAGGAAGACTACACGGCCATTACCAGCCGAGCCGACGCTAATGGCACAGCGAAACAG
CGTGCCTTACGTTGCCTCTCGGCAAAGACGGAAACAACCGAATGAGAAAGTGAGGAAAACCACAATGGTTTATGAAGGCCACCTTCGAACAAAACGTTCCCGGGAGGCTAGAGAGTCGCATCGGTAAATGGGTTTCCACCAAAACGCAGAACAACTCA
CAGGATGATAAGAAGATTGAATAGAGTCAAAGTTCCACGAGCCTCGAGCACATAATACGGGGCTAACCGTCACGCATGGGGGAGAACTCCGTTAAGATTTTTTCTTGACAGTGAAGAAAAGTAAAACAAAAAAATCACGACAGGGCGAGAGCAACGAA
GGGGACCTCACAAGCAACTCTCCTGATGCCTATCTGACACCAGCCCGCCATACCAGCAATCATGTTAGAGGGCCTCCAACCGCCGGTCCGTCCCACACCGATGGGACCTCCCACGGGCGCAAGACCTCGCGACGTTCTCGCTGACGTACTGCGAAGA
GATCCGTGCACATCGACCCGCCTGGCAAGCCGGCCCCGACGACATGCTAGCTTCACGCCGTGCAGCGCCGTCGCTCGGCCACACCAACTGACTGACCACCCCCCGACTACCCCGCTGTATCCTCTACTGCGCCGACAGTGGAACCGATGAAACTCAA
ACAGGTCCCAATGAAAGTCAAGACTGCCCAAACCGTCCATCATAAGAGAAACTCAATACCCCCGACGACCCATCCAGCCCCATACCCACCCAAAGGGAAACCATGTCCTGCTCGCGGCGGACACTAAAGCGATCAGGACCCAGTCCATCCCGTTTGAG
TCGATAAACACCCAGAACCGACAAACCTCACACACTCCAAGGACTGAAGAACTGAGAAATACCGACCCAGGAAGCCTTCGCGTTGTGCACTCCACTGCAATCAACAGCCTACATGGATTCGTACGGCACTGTCAAGCACATGCTCTCTGCGACTTCAG
CAAATGCGAAGACGTAAATCTACAGGCACCTGGATTTCGCAGCAACAAGCCTAGAGGTGTCCGACAGCCTCATGGTATCAACCCCGACGTGTCCCCCAGGCTCGCATGGCAGTTCCGGATCCCAAGGACCAATAGTCCACACGCCACTAGTTCGAATG
TTGCAGCAGCATCGGCAAAACCAACGAAAAACCACACCTCGGTGGTGTAAGCGCCGGACGGGTACCCCACACGACCCGGTCTTGTCCACATGGAAAGTACGAATGGAACTCGCATCTGACAGCCATAGACCGGTCCCAGCAACGCTACGGGGGCAAC
GCACCCAGACCGAAATCTCTAACCTAAATCTCCAACAAAGAACATGCCAGTAAAAGGTGAACAACCGCCGTCATCAGCCTACAGCTATCGATATTGCCGTAGCGGGATCATCCCCAAACGCGGGCGGCATCAATGGGAAATGCCGGAAATCCACATAC
CTGGACGCGCTCGGCGGCCTCGACCCCAGGACTCAAACACCCATACAGCTCGGTCCCCGCTCGGGACAGTAGTAAACGGAAACCGTGCACACTAGACCCGCCTCCAGAAGCTCGTCAAGCCTAGTAGGTAATACCAACGCACCTCAGAGATGAGGGC
GGTAAGTGCCTTTCCGGCAAGAATCGCTAAACCCCGCACGCCGTGICCCGACGCCCCCGGCGGAAGGATGTGGCGGGCACTTGGGTACGTCCIADDAIGAGGAACGCCTGGTTTGACCGGGACTTATGCGACGCTCGGGGGAACCCCATTGCCTCGGT
AGGTCGAAAGCGACTAGGGTCCCGATCGGGCTTGTCGTTGCGCTGTACCTGATCGCCAAACCCGAGCTACACCGGCCAGCCACCTATCACCTCCGCAGGCGTGACGCCCGGGCGAGCGCCCACGACCAGGGCCCGACGCAACATTGCGATGGCGCC
GCGTGCGCGAATGTACCCGGGTTAAGGTCAAAGCCGTAGCCAAGTGGGCGGTCCGAGGGGCGGAAGAGIACACTAAAGCTGGGCCCGGACCGGCGACCAGCAGCGTGAGAGTCCCCCAATACTTCGTTGACGGTACATCAAGCCGCGCACCCCGAAG
GCACCAGGAGTAAGCAGCATGACACCAGCAACGCTACCAGACCCACATGCAGCGTCGCCGTGGCGACTCTCTCCCATGTTCCCCCCAACACCAATAATAGGCAGCCAGGCCAAAAATGACTGATGCTATGACGCCCTCCGGCCCAAATGGAGAGAAA
CCCCCCGGAGCAGCATCAGTGGGCCCGCCTCAAAGGACCAACCCCGAGGCCCCCTCTTTGCCACCGACAGCAGCGAGGCACCGAAACCTACTAGGCGTTCGTCCAAACGTAGGTAAAGACATCTGCGCACCAGTTTTGCACGACTAAAAGGAATTGT
ACAGGGGCCATACCCCCAAACACCAATGACGGCTTCTTGCCTTACCCCGGGGGGTCCTGCGCACGCTTCGAGCCAATCCCCCACCGCTCAAGAACCTACCAACAACCCCCACGAGCGCCAAACACCCTACAAATACGAGACACACGCGAACGGTACC
GGTCAGCCCCTTCGGACCAAATCCCCGACCTAAGCACTACCTCAACAAAGCAAAACCCCCAGGGCAACACCCACGTACAAAATATGAAAACGCGGTAAATCCGTCACAGCCCTAACTATTGTTAGGAGGGGTGTGGACGCACACTGCCCCGGGAGATA
TAGGATGAGTCGCCTATCGAAGCATGCGCCACGCTCCCTCTGGGTCGGCAAAGCGGCTGGTCGTGGAATATGGCCCCGGGGTGCGGTGGTGTGAACCGCCCTCGAGCCAGCACGCTTCTAAACACCCCAGTGGATCGTCGGACAAAGACGCGAGTA
GAGCACAAATCCGGCGCAGAAAGCGAAAGGGCCGGCCAACAAAAACACTAGAAACCCACCCGGACAGAAGTTGGGGCGGGAAAGGCAAATTCGGAACTCCCGTAGTACGTCAGTTCTCCGCGAGACTGCAATTCAGCAAACGCAGACTGGAGCACAA
ACGACGTCATACCCTCGCGGGCTCGCACGGCCAGGGGTGGAACACCACCTGCAGGCCTGTACAGAGATCGGGCGGTCCGGTCICCCCCACCCCCCTCACGAGAACATTCAAACGGATACATGGGACTCGATGGCCCACAGAAACATACAGGACTGCG
GCACTGCGCGCTACCCGCAGACAAACCCGCCCCAATAAAAAACCGGACATCGTTCCCTGGCTTGCGACTATAAGTCGCGACGACAAAACTCTTTGCATCGGGCTCGCAGACAGATCTGCGAACCGCTCGCCCGCAATAGACGGGAGATGTATCACGTC
AGTAGCCCGCGTTGCGGACAACAACGAGACCCCGAACAAAAAGACGACACGAAACCCCAGGGGCACCGCAGAACTAGTATACCAACGTGACCCCCGCGACCAGAACCCAAGCCTCTCCTTGGGGCCTCAATTGTAATATACAGATGACCGACAACAG
ACACCACAGTCGCCTCAGTTTCCCGGCGTAAAACAGCAGCCCTGATCCCTGCAGAACGCACGTGTCTAAACTAGCATCAGAGAACGCACCACAGCATGTGCCCTCAAATTGCCCAAGGGGCCCGAGTCCCTTCGTTGCGTTCACCGGCCACTCGGCCC
GCTCACTCAAGACGACCCTGGACATCTACGAGAAAAAGCCAGGCCAATAAGCCGATAAAACCCACGTCAATAAAGGCGCGGAACCGTCGGGCACCACCGCCGGCCGACGAGCTCCCGACTTCAACCACGCAAACACCTAAGAACTAAACCAGCACAT
A
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15
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GG GG AG AG AA AA AG AA AG AA
Do individuals with a history of heart disease have
genotypes that differ from those without heart disease?
~35,000 individuals with coronary artery disease compared to
~260,000 individuals without coronary artery disease*
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Number of alleles seen in individuals :
Allele at rs4977574Coronary Artery
Disease
Healthy
Controls
G 36,995 31,907
A 256,744 267,224
Frequency of G in CAD = 36,995
(36,995+256,744)= 0.13 Frequency of G in Controls =
31,907
(31,907+267,224)= 0.11
This difference in frequency is highly unlikely to occur by chance.
* Motivated by van der Harst and Verweij, 2018: https://goo.gl/CS1vYr
=Probability of disease for your genotype
Probability of disease for a reference group
Relative Risk
My relative risk for
my genotype at
rs4977574 is ~1.5
For women of my age, ~5% have coronary artery disease
my risk is ~7%
Putting risk in context…
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rs4977574
Genetic discoveries since 2006
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Associations for CAD over the genome: 956
The Data!
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My Genotype My Genotype
rs1008898 GG rs4766578 TT
rs10121140 AG rs4803455 AC
rs10456100 CT rs4894803 AG
rs10951983 GG rs495828 GG
rs11099493 AA rs603424 AG
rs11556924 CC rs604723 CC
rs11591147 GG rs6426551 AG
rs1169288 CC rs6460942 TT
rs1223583 GG rs6511720 GT
rs12740374 GT rs6905288 AA
rs13010737 AG rs7342694 CT
rs15285 CT rs7412 CC
rs17114046 AA rs7502499 AG
rs2107595 AG rs7604735 GT
rs2454899 GG rs7795996 AA
rs2546343 TT rs8069437 CT
rs2880099 AC rs877549 GG
rs3732837 AT rs9349379 AG
rs3918226 CC rs9515203 CT
rs4299376 GG rs964184 CC
rs4646248 CT rs965652 AA
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IN SUM…
GENETIC
RISK
SCORE
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shh!
27New Scientist, 20 March 2019
Genetic Literacy Project, April 11, 2019
Science News, April 8, 2019
Scientific American, April 4, 2019
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It’s all relative…
Heritability = proportion of risk that is due to genetics
G
E
G
E
GE
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Figure 1e fromWang et al. doi:10.1038/ng.3931
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Genetics Genetics PLUS
Environment
My
dise
ase
risk
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Genetics Genetics PLUS
Environment
My
dise
ase
risk
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From my mom
R r
From my
dad R
r
RED HAIR
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• Recessive trait
• Caused by
mutations in a
gene called the
melanocortin 1 receptor (MC1R)
RR Rr
Rr rr
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Stephanie, your genetics make you unlikely to have red hair.
• Published: 10 December 2018
• An additional 8 genes were found that are associated with red hair.
• MC1R only explained 73% of a person’s “risk” of red hair
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“I’M STILL LEARNING.” –MICHELANGELO (as is Science!)
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42Figure augmented from: https://commons.wikimedia.org/w/index.php?curid=68544125
Central
Dogma of
Biology
…extended
Q & A
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• Over the past two decades, scientists have discovered a large number of places is our genome that affect YOUR health.
• The impact these have on YOU is relative to…• the rest of your whole genome and• your environment.
• Science is now moving to combine information over your genome while taking into account your environment to better assess disease risk.
• We’re still learning! (Shh: we’re not always right.)
• Participate…and go out and get cheeky with it!
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