The document provides an overview of the Human Genome Project (HGP). It describes the HGP's goal of mapping and sequencing the entire human genome. The HGP was an international research effort that worked alongside a private company, Celera Genomics, to complete a rough draft of the human genome by 2000. The completion of the HGP marked a major scientific achievement and has transformed fields like medicine, biotechnology, and genetics by providing a comprehensive map of the human genetic code.

1. Abhinav Srivastava, Ph.D
Director
Indian Biosciences and Research Institute
C-50, Sector-02, NOIDA-201310, Uttar Pradesh email: director@ibri.org.in

2. INTRODUCTION

3. GENOME
The hereditary material of all multi-cellular
organisms is the famous double helix of
deoxyribonucleic acid (DNA), which contains all of
our genes.

4. All our genes together are known as
“GENOME”.
The entire genetic makeup
of the human cell nucleus.

5. HUMAN GENOME
PROJECT

6. HUMAN GENOME PROJECT
 The Human Genome Project (HGP) was the
international, collaborative research program
whose goal was the complete mapping and
understanding of all the genes of human
beings.
 Genes carry the information for making all of the
proteins required by the body for growth and
maintenance.
 Made up of ~35,000-50,000 genes which code
for functional proteins in the body.

7. GOAL OF HGP
 Identify all of the genes in human DNA.
 Determine the sequence of the 3 billion
chemical nucleotide bases that make up
human DNA.
 Store this information in data bases.
 Develop faster, more efficient sequencing
technologies.

8. GOAL OF HGP :
 Develop tools for data analysis.
 Address the ethical, legal, and social
issues (ELSI) associated with the project.

9. Two Different Groups W orked to Obtain
the DNA Sequence of the Human
Genome
 The HGP is a multinational consortium
established by government research
agencies and funded publicly.
 Celera Genomics is a private company
whose former CEO, J. Craig Venter, ran
an independent sequencing project.
 June 6, 2000, the HGP and Celera
Genomics held a joint press conference to
announce that TOGETHER they had
completed ~97% of the human genome.

10. PUBLICATION
 The International Human Genome Sequencing
Consortium published their results in Nature,
409 (6822): 860-921, 2001.
“Initial Sequencing and Analysis of the Human
Genome”
 Celera Genomics published their results in
Science, Vol 291(5507): 1304-1351, 2001.
“The Sequence of the Human Genome”

11. METHODS AND
TOOLS

12. STRATEGY INVOLVED
 This is regarded as the most ambitious project
ever undertaken by man.
 Strategy may be grouped into following three
stages:
i) Mapping
ii) Sequencing
iii) Functional analysis

13. MAPPING
 The first major goal of the project is to prepare
high resolution or saturated genetic and
physical maps of human genome.
 Molecular markers have been used to produce
maps of all the human chromosome.
 By August 2000, over 9,300 markers had been
mapped to particular chromosome. Therefore,
any new DNA sequence (i.e., an additional
marker) can be easily linked with these
markers.

14. SEQUENCING
 Determination of precise order of nucleotide in
DNA.
 There are following techniques for the DNA
sequencing:
i) Chain termination method By F.Sanger & A.
R. Coulson
ii) Chemical degradation method By A.
Maxam & W. Gilbert
iii) Automated DNA sequencing

15. CHAIN TERMINATION
METHOD
 Nucleotide analogs (called dideoxynucleotides
or ddNTP) are incorporated into DNA during its
synthesis together with normal nucleotides
(called deoxynucleotides or dNTP).
 When a ddNTP is inserted, the reaction stops =
chain termination.
 Four different reactions are performed.
 Each reaction contains either ddA, ddG, ddC, or
ddT.
 Autoradiography enable analysis of different
fragment lengths which correspond to different

17. CHEMICAL DEGRADATION
METHOD
 Double stranded DNA fragment to be sequenced is
first labeled by attaching a radioactive phosphorous
group to the 5’end of each strand.
 DMSO then added and the sample heated to 90°C,
degraded sample is allowed for GE.
 One strand is purified from gel & divided into foru
sample each of which is treated with one of the
CLEAVAGE REAGENT.
 The first set of reagent to be added cause a chemical
modification in the nucleotide for which they are
specific, making the strand susceptible to cleavage at
that nucleotide when an additional chemical is added.

19. AUTOMATED DNA
SEQUENCING
 This is carried out in the same way as the
chain termination method with only one
difference.
 Here we use FLUORESCENT LABELS to
label the strand instead of radioactive label.
 These labels are usually attached to the
ddNTP so each chain terminated molecule
carries a single label at its 3’end.
 Different fluorochrome can be used for four
different ddNTP.

21. FUNCTIONAL ANALYSIS
 The ultimate objective of the HGPis to
decipher the function of each of the genes
estimated to be present in the human
genome.

22. OTHER COMPLETED
GENOMES

23. MICROBIAL GENOME
 Ha e m o p hilus influe nz a e
 Es c he ric hia c o li
 Ba c illus s ubtilus
 He lic o ba c te r p y lo ri
 Stre p to c o c c us p ne um o nia e
AND MANY MORE !

24. PLANT GENOME
 A bid o p s is tha lia na
ra

25. INSECT GENOME
 Dro s o p hila m e la no g a s te r

26. RODENT GENOME
 M m us c ulus
us

27. ETHICAL, LEGAL & SOCIAL
ISSUES
[ELSI]

28.  The U.S. Department of Energy (DOE)
and the National Institutes of Health (NIH)
spend between 3-5% of their annual HGP
budgets toward studying the ELSI
associated with availability of genetic
information.
 This budget is the world’s largest
bioethics program, and has become a
worldwide model.

29. EXAMPLE OF ELSI
 Privacy legislation
 Gene testing
 Patenting
 Forensics
 Behavioral Genetics
 Genetics in the Courtroom

30.  Who should have access to this information ?
 Employers
 Insurers
 Schools
 Courts
 Adoption agencies
 Military

31.  How is privacy and confidentiality managed ?
 Affects on society’s perceptions and
expectations of the individual
 Who owns genes and DNA sequences ?
 The person (or company) who discovered it,
or the person whose body it came from?
 Should genetic information be the property
of humanity?
 Is it ethical to charge someone for access to
a database of genetic information?

32. APPLICATION
W hich branches of
biology will benefit from
this knowledge ?

33. MEDICINE
 Improvements in diagnostic
and therapeutic applications
 Implementation of
preventative measures.
 Increases in gene therapy
applications.

34. BIOTECHNOLOGY
 Production of useful protein products for use
in medicine, agriculture, bioremediation and
pharmaceutical industries.
 Antibiotics
 Protein replacement (factor VIII, TPA,
streptokinase, insulin, interferon…)
 BT insecticide toxin (from Ba c illus
thuring ie ns is )
 Herbicide resistance (glyphosate resistance)
 Bioengineered foods [e.g. Flavr Savr tomato
(antisense – polygalacturonase) to delay
rotting]

35. BIOINFORMATICS
 The newest, fastest growing specialty in
the life sciences that integrates
biotechnology and computer science.
 Involved in DNA sequence assembly
and analysis using computer-based
techniques to determine gene function,
regulation and control.
 Unknown gene sequences can be
compared to databases of known genes
to enable similarities to lead to
determination of an unknown gene’s

36. PROTEOMICS
 Investigates patterns and levels of
gene expression in diseased cells
that can be analyzed to build
databases of expression profiles.

37. PHARMACOGENOMICS
 Investigates SNPs and DNA
mutations associated with
disease susceptibility and drug
sensitivities.

38. DEVELOPMENTAL
BIOLOGY
 Regulation of embryonic
development.
 Regulation of the aging process.

39. EVOLUTIONARY AND
COMPARATIVE BIOLOGY
 Because DNA mutates at a
constant rate, comparisons of
DNA between different
organisms can provide
evolutionary histories.

40. SUMMARY
 The significance of the completion of the
human genome project cannot be
overstated.
 With the dictionary of the genome
available, the molecular mechanisms of
human health and disease will be
resolved.
 Armed with this knowledge a
transformation in medical diagnostics and
therapy is underway and will continue into
the next few decades.

41. REFERENCES
 Cook-Deegan R (1989). "The Alta Summit, December 1984". G e no m ic s 5:
661–3.
 Barnhart, Benjamin J. (1989). "DOE Human Genome Program". Hum a n
G e no m e Qua rte rly 1: 1. Retrieved 2005-02-03.
 DeLisi, Charles (2001). "Genomes: 15 Years Later A Perspective by
Charles DeLisi, HGP Pioneer". Hum a n G e no m e N ws 11: 3–4. Retrieved
e
2005-02-03.
 International Human Genome Sequencing Consortium (2001). "Initial
sequencing and analysis of the human genome." (PDF). N ture 409: 860–
a
921.
 Venter, JC, et al. (2001). "The sequence of the human genome."
(PDF). Sc ie nc e 291: 1304–1351.
 Sanger F, Air GM, Barrell BG, e t a l. (February 1977). "Nucleotide sequence
of bacteriophage phi X174 DNA". N ture 265 (5596): 687–95.
a
 Waterston RH, Lander ES, Sulston JE (2003). "More on the sequencing of
the human genome". Pro c N tl A a d Sc i U S A 100: 3022–4.
a c .


42. THANK YOU !