Cheek to Cheek:

Genetic Discoveries

and You

Stephanie A. Santorico, Ph.D.

Professor

Department of Mathematical & Statistical Sciences

Human Medical Genetics and Genomics Program

Stephanie.Santorico@ucdenver.edu

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Data Revolution

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~ 4

00

~ 1

3

~ 1

00,0

00

~ 5

00,0

00

~ 2

,500

0,00

0

~ 3

,200

,000

,000

=

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3,200,000,0006

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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

13

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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