The New Paradigm of Genomics

Transcription

1 The New Paradigm of Genomics Jun YU CAS-KLGSI, BIG,CAS June 26,

2 2010/12/29 For the First time: Whole-Genome Sequencing Delivers New Treatment Options for Twins with Rare Genetic Movement Disorder

3 Yes, it is here the era of personalized medicine when physicians use wholegenome sequence to improve medical care Whole-Genome Sequencing for Optimized Patient Management. Bainbridge et al Sci Transl. Med 3:87re /12/29

4 Cost Per Human Genome (USD) Current Direct Cost 2010/12/29

5 From HGP to New Paradigm The HGP Era ( ): One human genome done, and we ignored the differences among individuals The Post HGP Era: the HapMap Projects and hundreds of genomes done, and we realized that the differences among people are vast in numbers The New Paradigm: tens of thousands of genomes done, and we realized that we can map all sequence variations and tailor them to human health and disease status 5

6 In 2010 alone, the human genome sequencing projects and associated research and industry activity directly and indirectly generated: $67 billion in U.S. economic output $20 billion in personal income for Americans 310 thousand jobs. 2010/12/29

7 Dreams and Promises

8 Why New Sequencers? Bocklandt S, Lin W, Sehl ME, Sánchez FJ, Sinsheimer JS, et al. (2011) Epigenetic Predictor of Age. PLoS ONE 6(6): e doi: /journal.pone /12/29

9 What cheaper sequencing can do? Genome-centric goals: genome sequences and genomic variomes for population genetics and evolution Cell-centric goals: transcriptomes and proteomes for cell biology, physiology, and pathology Epigenome-centric goals: methylomes and nucleosome/histone marks for gene regulation and phenomes Ribogenome-centric goals: RNA editing/splicing (other than mrnas), mirnaomes, ncrnaomes, and chemical modifications for RNA-based gene regulations 9

10 Reverse transcriptase was discovered by Howard Temin at the University of Wisconsin Madison, and independently by David Baltimore in 1970 at MIT. The two shared the 1975 Nobel Prize in Physiology or Medicine with Renato Dulbecco for their discovery Beijing Institute of Genomics, CAS 10

11 The RNA World Is Early but Not Small! The RNA World (Gilbert) Ribosyme (Cech and Altman); In 1989, Thomas R. Cech and Sidney Altman won the Nobel Prize in chemistry for their "discovery of catalytic properties of RNA. In 2006, Craig Mello and Andrew won Nobel Prize on the discovery of RNA interference (RNAi) Beijing Institute of Genomics, CAS 11

12 Central Dogma Gets More Complex Central Dogma Modified Central Dogma Ribogenome CD Ribo Epigenome CD Beijing Institute of Genomics, CAS 12

13 Informational Track A & C Operational Track E Operational Track R Operational Track M

14 Operational Tracks The Complexity of Genomics: New Paradigm Phenotypes Informational Tracks Protein centric Mechanisms Epi proteincentric Mechanisms Chromosomecentric Mechanisms Metabolitecentric Mechanisms Organellecentric Mechanisms RNA centric Mechanisms Genotypes 2010/12/29

15 The Tempo-spatial View of Life Beijing Institute of Genomics, CAS 15

16 2010/12/29

17 2010/12/29

18 The Modern Synthesis in Physics Quantum mechanics Newtonian physics General relativity Subatomic objects Everyday objects Astronomic objects Copenhagen interpretation 2010/12/29

19 Reconciling Mendel with Darwin Mendelian genetics Darwinian selection modern synthesis mutation and recombination random drift and selection frequency of alleles

20 Francis Crick James Watson The Molecular Era of Biology DNA 双螺旋模型的建立 冷泉港实验室提供

21 molecular biology systems biology observational biology + Cue -Cue single genes and proteins interacting molecules variance in populations

22 Traditional View of Phenotype, Genotype, Environment, and Phenotypic Plasticity V P =V G +V E1 V P =V G +V E2 Ontogeny V noise : developmental behavioral and other type of noise V P =V G +V E + V 2 EG+V noise

23 Dream Projects and Tools 10,000 Human Genome Project The Human Ribogenome Atlas The Human Epigenome Atlas Disease-centric Projects (such as cancers and infectious diseases) Personalized genomics at single cell and single molecule levels 2010/12/29

24 Impact of Genetic Diseases on Adult Life

25 Rare Genetic Disorders Are Not So Rare 2010/12/29

26 GENETIC TESTS may be done for diverse purposes pertaining to clinical genetics, including the diagnosis of genetic diseases in children and adults; the identification of future disease risks; the prediction of drug responses; and the detection of risks of disease to future children. Pre-implantation diagnosis Prenatal diagnosis Newborn screening Carrier testing Diagnostic testing Pre-symptomatic testing Predictive testing

27 Tolerance Adjusting of Organisms to Ecological Factors Adaptation ( ) Migration ( ) Acclimation ) Aestivation ( ) Hibernation ( ) Dormancy Diapause Quiescence ( ) Camouflage ( ) Torpor

28 2010/12/29 Liu et al, (2011), Front Plant Sci 2:17.

29 2010/12/29

30 Germination: Epigenetic Control? 40% delayed 20% delayed Normal Pre-soaked for 2d Pre-soaked for 2d & dried for 2d

31 2010/12/29 Palm Date Fruiting

32 Challenging the Common Dogma Darwinian vs. Lamarckian evolution Gradualism vs. punctuated equilibrium Mendelian inheritance vs. epigenetics Ageing: genetic or environmental Twin differences Hibernation: why couldn t we? Menopause can we change the course? Obesity and metabolic syndromes Beijing Institute of Genomics, CAS 32

33 The More A Gene Is Used, the More Mutation It Accumulates Beijing Institute of Genomics, CAS 33

34 Thanks! 2010/12/29