DNA, the code of life

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DNA, the code of life Genome, the book of life
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The Human Genome Project

• International Coordinated Effort to Study
• Genomes of Human and Study Genomes of Humans and
  Several Other Organisms.
• 15 Years project 1990-2005 (1991-2003)
• MappingSequencing Components
• U.S. Funding NIH and DOE

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Completion of a Working Draft, June 26, 2000
ABCNEWS W A S H I N G T O N, June 26
Scientists announced today that they have
cracked most of the genetic code, unlocking the
secrets of human DNA.
WHO? 1. National Human Genome Research
Institute 2. Celera Genomics
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The Human Genome Project Goals
1993-1998 Physical Mapping DNA Sequencing Gene
Identification Technology Development Model
Organisms Informatics Ethical, Legal, and
Social Implications (ELSI) Training Technology
Transfer Outreach
1998-2003 Human DNA Sequence Sequencing
Technology Human Genome Sequence
Variation Functional Genomics Technology Comparati
ve Genomics Ethical, Legal, and Social
Issues Bioinformatics and Computational
Biology Training and Manpower
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National Human Genome Research Institute
Genetic Physical Mapping
Human DNA Sequence
Short Gun Sequencing (with the human genome
project data)
CeleraGenomics
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Genetic Medical Disorders
Without HGP - 5-10 Years - May not be possible.
With HGP - 1-2 Years - Feasible
Single gene Multifactorial
Gene Mutation identified
Diagnosis (Preventive Medicine)
Gene therapy
Biology of Diseases
Prevention and Treatment
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Genetic Susceptibility of Nasopharyngeal Cancer
Geographical distribution
High - risk group The Southern
Chinese,
Eskimos Intermediate - risk group The
Southeast Asia Low - risk group The North
America, Europeans
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EBV Pathogenesis
EBV
Oropharyngeal Epithelium
Infectious Mononucleosis
Acute Infection
B Lymphocyte
Endemic Burkitt Lymphoma
latent infection
Mutation
Malignancy
Nasopharygeal Carcinoma
Nasopharyngeal Epithelium
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How EBV enters nasopharyngeal epithelium and
cause cancer, CR2 or pIgR? Are there genetic
susceptible for this process? Hypothesis CR2 or
pIgR is a NPC susceptibility gene.
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Searhing for Mutation or Linkage Disequilibrium
Marker disease normal
149 30
8 70
Ancester
RR 8.12 95CI (4.20-15.70)
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Thai case 110 control 104 Chinese case
42 control 107 Total case 175 control 317
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Ethnic adjusted Odd Ratios CR2IVS2-848C T
0.96lt1.47lt2.26 PIGRIVS3-156G 0.66lt0.88lt1.18 PIGR1
093G A 0.76lt1.03lt1.40 PIGR 1739C T
1.51lt2.26lt3.25 plt0.0001 Homozygous PIGR 1739C
1.72lt2.71lt4.23 p lt 0.00001
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Nature Reviews Genetics 1 48-56 (2000)

• Functional Genomics
• the whlole genome
• GeneRNA array
• Proteomics
• Bioinformatics
• Integrate genetics, Computer Sciences,
  Biochemistry, Cell Biology, Structural Biology,
  Physiology

DNA arrays for transcriptional profiling
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Genetic Medical Disorders
Without HGP - 5-10 Years - May not be possible.
With HGP - 1-2 Years - Feasible
Single gene Multifactorial
Gene Mutation identified
Diagnosis (Preventive Medicine)
Gene therapy
Biology of Diseases
Prevention and Treatment
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• Human genome array for
• reutine clinical diagnosis?
• Hypertension
• DM
• Psychosis
• Stroke
• Asthma

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Lance Liotta1, 2 Emanuel Petricoin1
Nature Reviews Genetics 1, 48-56 (2000)
MOLECULAR PROFILING OF HUMAN CANCER
Discovery of diffuse large B-cell lymphoma
(DLBCL) clinical subtypes by DNA array profiling.
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Genetic Medical Disorders
Without HGP - 5-10 Years - May not be possible.
With HGP - 1-2 Years - Feasible
Single gene Multifactorial
Gene Mutation identified
Ethical, Legal, and Social Implications (ELSI)

Diagnosis (Preventive Medicine)
Gene therapy
Biology of Diseases
Prevention and Treatment