The Human Genome Project

Presented By:

Madan Sharma HILS Paonta sahib

sharmamaddy32@gmail.com 7/25/12

INTRODUCTION

Until the early 1970s, DNA was the most difficult cellular molecule to analyze. DNA is now the easiest molecule to analyze Easy to isolate a specific region of the genome produce a virtually unlimited number of copies determine its nucleotide sequence overnight.
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What is the Human Genome Project?

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U.S. govt. project coordinated by the DOE and NIH, launched in 1986 by Charles De Lisi. Definition: GENOME the whole hereditary information of an organism that is encoded in the DNA. Collaboration would be open to centers from any nation 20 centers from 6 countries US, UK, China, France, Germany, Japan
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Aims of the project:

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to identify the approximate 100,000 genes in the human DNA. determine the sequences of the 3 billion bases that make up human DNA. store this information in databases. develop tools for data analysis. address the ethical, legal, and social issues that arise from genome research.
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History of human genome project

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Human Genome Project, 1984-86

DOE was interested in genetic research regarding health effects from radiation and chemical exposure NIH was interested in gene sequencing / mutations and their biomedical implications of genetic variation 2 meeting held at Santa Crug And Santa

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Human Genome Project, 1988

Reports from OTA, NRC, and an Ad Hoc Advisory Committee on Complex Genomes All reports supported the development of the Human Genome Project, with parallel projects for other model organisms Congress agreed to appropriate funds to support research to determine the structure of complex genomes

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Human Genome Project, 1989

Congress required NIH and DOE to prepare a detailed plan for the appropriations hearings NHGRI was created as a new division of NIH with budget estimated at 1% of total for NIH

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Human Genome Project, 1990 Five Year Plan

Construct a high resolution genetic map of the human genome Produce physical maps of all chromosomes Determine genome sequence of human and other model organisms Develop capabilities (technologies) for collecting, storing, distributing and analyzing data
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Human Genome Project, 1990 Additional Goals

Ethical, legal, social issues (ELSI) Research training Technology transfer began with a recommended budget of $200 million per year, adjusted for inflation 15 years, $3 billion

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Human Genome Project, 1993 Revised Goals

Revised because of rapid progress

Automated DNA sequencing technology Genetic markers could be assayed using PCR Better cloning vectors for large genomes Better computational methods for genome assembly

Greater focus on genes

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HUMAN GENOME PROJECT(1995)

First organism sequenced i.e Haemophilus influenzae Maps based on sequence tagged sites, human genetic map, transcript map published

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Human Genome Project, 1998 New Five Year Plan

Finish complete human genome sequence by 2003 (50th anniversary of double helix by Watson and Crick)

Draft sequence finished in July, 2000 Complete sequence to be published in 2001

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Human Genome Project, 1998 New Five Year Plan

Complete sequence of C. elegans by 1998 Published in 1998 Complete sequence of D. melanogaster by 2002 Published in 2000 Complete M. musculus genome sequence by 2005

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How Did the Draft

Click to edit Master subtitle style

Sequence Develop?
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Draft Sequences, 2001

International Human Genome Sequencing Consortium (public project)

Initial Sequencing and Analysis of the Human Genome. Nature 409:860-921, 2001

Celera Genomics Venter JC et al. (private project)

The Sequence of the Human Genome. Science 291:1304-1351, 2001.

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CHALLENGES

Data were generated in labs all over the world Organism is diploid, extremely large genome Large proportion of the human genome consists of repetitive and duplicated sequences Cloning bias (under-representation of some region of the genome)
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Benefits of Human Genome Project research

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improvements in medicine. microbial genome research for fuel and environmental cleanup. DNA forensics. improved agriculture and livestock. better understanding of evolution and human migration.

How is each area benefited specifically by the Human Genome Project?

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Improvements in medicine: improved diagnosis of disease. Microbial research: new energy sources, bio fuels. DNA forensics: identifying potential suspects at a crime scene. Agriculture: more nutritious produce. Evolution and human migration: study migration of different population groups based on female genetic inheritance.

- Risk assessment: reduce the

Categorization of genes
23.2% Expression, replication, maintenance 21.1% 17.5% the cell 38.2% 7/25/12 Signal transduction Biochemical functions of

Other

APPROACHES TO SEQUENCE

Shotgun Phase
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Hierarchical shotgun sequencing used to produce draft sequence of 90% of the genome

Finishing Phase
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Fill in gaps and resolve ambiguities Fragments must be sequenced ~ 10 times to reach accuracy of >99%
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In 1981, sequencing 12,000 bp took ~1 yr In 2001, sequencing 12,000 bp takes < 1 min

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1. Dideoxy Sequencing 2. Shotgun Sequencing

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Ethical, Legal, and Social Issues

Privacy and confidentiality of genetic information. Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. Psychological impact, stigmatization, and discrimination due to an individuals genetic differences. Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making. Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and quality control measures. 7/25/12

ELSI Issues (cont.)

Uncertainties

associated with gene tests for susceptibilities and complex conditions Fairness in access to advanced genomic technologies. Conceptual and philosophical implications regarding human responsibility, free will vs genetic determinism, and concepts of health and disease. Health and environmental issues concerning genetically modified (GM) foods and microbes. Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials.
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Beyond the HGP: Whats Next?

HapMap
Chart genetic variation within the human genome

Systems Biology
Exploring Microbial Genomes for Energy and the Environment

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Genomes to Life:
A DOE Systems Biology Program
Exploring Microbial Genomes for Energy and the Environment

Goals
identify the protein machines that carry out critical life functions characterize the gene regulatory networks that control these machines characterize the functional repertoire of complex microbial communities in their natural environments develop the computational capabilities to integrate and understand these data and begin to model complex biological systems 7/25/12

HapMap
An NIH program to chart genetic variation within the human genome

Begun in 2002, the project is a 3-year effort to construct a map of the patterns of SNPs (single nucleotide polymorphisms) that occur across populations in Africa, Asia, and the United States. Consortium of researchers from six countries Researchers hope that dramatically decreasing the number of individual SNPs to be scanned will provide a shortcut for identifying the DNA regions associated with common complex diseases Map may also be useful in understanding how genetic variation contributes to responses in environmental factors

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Future Challenges: What We Still Dont Know

Gene

number, exact locations, and functions

Gene regulation DNA sequence organization Chromosomal structure and organization Noncoding DNA types, amount, distribution, information content, and functions Coordination of gene expression, protein synthesis, and posttranslational events
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Evolutionary conservation among organisms Interaction of proteins in complex molecular machines

Predicted v/s experimentally determined gene function Protein conservation (structure and function) Proteomes in organisms Correlation of SNPs with health and disease Disease-susceptibility prediction based on gene sequence variation
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Complex systems biology including microbial consortia useful for environmental restoration

Developmental genetics, genomics Genes involved in complex traits and multigene diseases

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Before fishing plan ahead

always

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THANKS
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