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TRANSCRIPT
Jeong-Sun Seo, M.D., Ph.D
Precision Medicine Center
Seoul National University Bundang Hospital
Macrogen Founder
Nov. 19th, 2019 Global Leaders Forum 2019
Korean Reference Genome
for Asian Precision Medicine
아시안 정밀의학을 위한 한국인 게놈 지도 완성
PART I
From Human Genome Project to Precision Medicine
인간게놈계획에서 정밀의학까지
left-handed:17%
Auricle feature:44%
Wet earwax: 88%
Family history of male boldness
in western : 56% anxietas tibiarum(restless legs):13%.
Images from http://www.23andme.com
Lactose intolerance: 22%
Family history in migraine:41%.
Absolute pitch:14%
도서관에 있는 책의 정보 풀기는 가능한가.
인류는 자신의 몸에 있는 생명암호를 풀 수 있을까.
인간이 자신에게 도전하다.
Human Genome Project (1990. 10. ~ 2000. 6)
June 26, 2000
Human Genome Project (1990-2000)
Francis Colins
Craig Ventor
Crown jewel
in health science
Major characteristics of 21st century 1. Globalization 2. Technology 3. Increase of aging population
Can the U.S. Meet
Its Aging Population’s Health Care Needs?
Chronic disease: $3 out of every $4 of U.S health care spending
Annual cost (2009); $1.875 Trillion
Healthcare as share GDP: from 17.6% of GDP (2009) to 37% of GDP(2050)
2015, The Year of Precision Medicine
President Obama’s State of the Union Address:
January 20, 2015
“Tonight, I'm launching a new Precision Medicine Initiative to bring us closer to
curing diseases like cancer and diabetes — and to give all of us access to the
personalized information we need to keep ourselves and our families healthier.”
President Barack Obama, State of the Union Address, January 20, 2015
Beery Twin’s Story
DRD(Dopa Responsive Dystonia)
Nic Volker’ Story
Nic underwent 160 surgeries before having his genome sequenced to diagnose his intestinal disease.
XIAP gene, inflammatory bowel disease
“ We ended up doing a core blood transplant; 42 days later he was eating. He had been on total parenteral nutrition for 9 months; after treatment, he enjoyed steak. Nic is now 9. It's coming up on 4 years since his transplant and his gut disease completely resolved. It's a great story."
Advancing Healthcare Through Personalized Medicine
Precision Medicine
For every person they do help (blue) , the ten highest-grossing drugs
in the US fail to improve the conditions of between 3 and 24 people (red)
“ One size does not fit all “
For every person they do help (blue) , the ten highest-grossing drugs
in the US fail to improve the conditions of between 3 and 24 people (red)
Precision Medicine
EMR Big data analysis
Genomics
Lifelog
Precision Medicine?
유전체정보, 질병기록 그리고 모바일 헬스 정보를 빅데이터 기술로 처리하여 질병을 예측함
Participatory Medicine
Preventive,
Predictive,
Personalized Medicine
Genomics is Failing on Diversity
Nature 538:161 (2016)
Asian
“In 2009 analysis, 96% of
participants in GWAS were of
European descent.”
Asian populations are still left behind on the road to precision medicine.
“Much of this rise, is a result of
studies on populations of Asian
ancestry.”
“The proportion of non-European
decent in GWAS increased up to
nearly 20% in 2016”
NIH Director Dr. F. Collins’ s Visit to GMI-SNU, Korea
Sep. 8th 2015. at GMI-SNU
Dr. Collins
Asian Precision Medicine Initiative
PART II
Korean Genome Map Completed
한국인 게놈 지도 완성:세번의 시도
First Approach(2009): Mapping to reference genome
Second Approach(2016): De novo Assembly
Third Approach(2019): GenomeAsia 100K Project
한국인 게놈 지도 완성:세번의 시도
Nature (2009)
SNPs of each ethnic group
Stephen Kingsmore Rady Chilidren’s Hopsital Jong Il Kim
SNUMC
Northern Asian Genome Sequencing and Analysis, Nature 2009
북방계 아시아인 게놈 분석
Green et al., Nature 470 (7333) 10 Feb. 2011
2011년 2월, 인간 게놈 프로젝트 10주년 기념 네이처 특집호
북방계 아시아인 유전체 논문 (서울의대)
백인 유전체 논문
흑인 유전체 논문
남방계 아시아인 유전체 논문
First Approach(2009): Mapping to reference genome
Second Approach(2016): De novo Assembly
Third Approach(2019): GenomeAsia 100K Project
한국인 게놈 지도 완성:세번의 시도
De Novo Assembly of Korean Human Genome
De novo assemblies are orders of magnitude slower and more memory intensive than
mapping to assemblies.
Sequencing De novo Assembly Complete genome
PacBio (~101 X)
Long reads 303 Gb
Illumina (~72 X)
Short reads 216 Gb
BioNano (~200 X)
Optical maps 600 Gb
32,026
AK1 BAC Clones
Gap Closing by AK1 Scaffold and BAC Clones
Seo JS, et al, Nature; 538:243-247, Oct, 2016
• The size of Gap_367 and Gap_368 is 50kb.
• 144 kb of novel sequences, indicated in yellow, are added to the human
reference.
• BAC clones and BioNano Genome map validate this novel sequence.
De Novo Assembly of Korean Genome
“This is the most contiguous human genome mapped to date, providing a population-specific reference genome and vital data for genetic scientists generally”
Nature Press, Oct. 2016
아시안 표준유전체 연구결과 네이처지에 발표 (2016. 10)
First Approach(2009): Mapping to reference genome
Second Approach(2016): De novo Assembly
Third Approach(2019): GenomeAsia 100K Project
한국인 게놈 지도 완성:세번의 시도
Towards diversity in genomics: GA100K
Significance of Asian genome in precision medicine
GA100K (2016-2020) Project:
Indigenous Asian Genome Project
Founding Member
Partner
- 1,739 population scale
genome sequencing
- 64 countries
- More than 200 ethnic
group
113
598
156 68
70
70
52
152 35
100
Northern Mongolian Cohort
Genetic Admixture in Asian Populations Asians have diverse population structures
AFR EUR SAS SEA OCE NEA AMR
Mongolians share ancestry with East Asian, Siberian, and native American populations
Asian is the population with diverse genetic admixtures relative to other ethnic groups.
M
Maternal Ancestry
from Asian Mitochondrial Whole Genomes
1,178 Individual mitochondrial genome
GA100K unpublished data
• 4 distinguishable
patterns of
mitochondrial whole
genomes
(European, African,
SAS, and NES)
• Mongolian data
reveals that the
maternal ancestry
of NES is related to
SAS and Native
American.
PART III
Digital Transformation & Genome Industry
디지털 전환과 게놈 산업
1. 3D Metal Printing
2. Artificial Embryo
3. Sensing City
4. AI for Everybody
5. Dueling Neural Networks
6. Babel-Fish Earbuds
7. Zero-Carbon Natural Gas
8. Perfect Online Privacy
9. Genetic Fortune-Telling
10. Material Quantum Leap
10 Breakthrough Technologies 2018
2018 March-April
Abdominal Aortic
Aneurysm
Age-related Macular
Degeneration Alzheimer’
disease
Asthma
Celiac disease
Colorectal Cancer
Crohn’s disease
Exfoliation Glaucoma
Atrial Fibrillation
Direct to Consumer Genetic Testing Personal genome service
0.51
0.77 0.14
0.23
2.99
1.00
0.86
0.60
0.18
Atrial Fibrillation 2.99 ?
Your lifetime risk of Atrial Fibrillation
This report is for people of European ancestry, which does not match for people of unknown gender and ethnicity.
When in Doubt, Spit It Out “알고 싶으면 침을 뱉어라”
“23andMe” DNA test
Home DNA Kit
- More than 20M people have a DNA story now -
AncestryDNA has 10 million
customers in their database,
adding over 2 million so far this
year
23andMe and AncestryDNA are
the two largest and well known
direct-to-consumer (DTC)
genetic testing services.
23andMe has grown to 5 million
customers in the 10 years.
Everybody’s doing DNA tests
Genome Biology 2018 19:120
북미지역 2000만명 유전자 검사 결과 보유
Growth in DTC Genetic Testing
Psomagen* Personal DNA testing in Amazon Black Friday 2019. 11.29
*Psomagen was formerly Macrogen US
10M Korean Peninsula Asian Genome Project Consumer-driven Genome Project ($50/person)
10M People in Korean Peninsula
- 4M South Korean
- 4M North Korean
- 2M Asian who live in Korea
Establishment of telemedicine in North Korea
Establishment of Unified-Korean precision medicine through
10M Korean Peninsula Genome Project
Seoul National University Bundang Hospital
Healthcare Innovation Park
“ Connecting the dots ”