The document provides information about the Human Genome Project including: 1) It began in the late 1980s as a collaboration between the U.S. Department of Energy and the National Institutes of Health with a goal to map and sequence the entire human genome. 2) By 2003, the project had completed mapping the approximately 3 billion DNA base pairs that make up human DNA and identified over 30,000 human genes. 3) The project's completion enabled major advances in fields like medicine, biotechnology, and personalized healthcare by providing a better understanding of human genetics.

2. Name
Aafaq Ali,Asad
Noman
Class
M.Phil 1st Sem
Topic
Human Genome Project
Presented To
Sir Umair Malick
Department Of Botany
University Of Lahore(Sargodha Campus)

3. The Human Genome Project

4. Introduction
 Until the early 1970’s, DNA was the most difficult
cellular molecule for biochemists to analyze.
 DNA is now the easiest molecule to analyze – we can
now isolate a specific region of the genome, produce
a virtually unlimited number of copies of it, and
determine its nucleotide sequence overnight.

6. What is a genome?
A genome is an organism’s complete set
of DNA, including all of its genes. Each
genome contains all of the information
needed to build and maintain that
organism. In humans, a copy of the entire
genome—more than 3 billion DNA base
pairs—is contained in all cells that have a
nucleus.

7. History Of Human Genome
project
In 1984-86
DOE(Department of Energy) was interested in
genetic research regarding health effects from
radiation and chemical exposure.
NIH(National Institutes of Health) was interested
in gene sequencing / mutations and their
biomedical implications of genetic variation.

8. Human Genome Project,
1988
Reports from NRC(Nuclear Regulatory
Commission)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

9. History of Human Genome Project,
 1983 Los Alamos Labs and Lawrence Livermore National Labs,
both under the DOE(Department Of Energy), begin production
of DNA cosmid libraries for single chromosomes
 1986 DOE announces HUMAN GENOME PROJECT
 1987 DOE advisory committee recommends a 15-year multi-
disciplinary undertaking to map and sequence the human
genome. NIH(National Institutes of Health) begins funding of
genome projects
 1988 Recognition of need for concerted effort. HUGO founded
(Human Genome Organization) to coordinate international
efforts DOE and NIH sign the Memorandum of Understanding
outlining plans for co-operation

10.  1990 DOE and NIH present joint 5-year Human
Genome Project to Congress. The 15 year project
formally begins
 1991 Genome Database (GDB) established
 1992 Low resolution genetic linkage map of entire
human genome published, High resolution map of Y and
chromosome 21 published
 1993 DOE and NIH revise 5-year goals
 IMAGE consortium established to co-ordinate efficient mapping and
sequencing of gene-representing cDNAs (Integrated Molecular Analysis of
Genomes and their Expression)

11.  1994 Genetic-mapping 5-year goal achieved 1 year
ahead of schedule
 Genetic Privacy Act proposed to regulate collection, analysis, storage and use of
DNA samples (endorsed by ELSI)
 1994-98 Tons of stuff happens that continues to
advance the project
 1998 Celera* Genomics formed
 New 5-year plan by DOE and NIH
 1999 First chromosome completely sequenced
(Chromosome 22)
 2000 June 6, HGP and Celera announce they had
completed ~ 97% of the human genome.
 2003 April 25, HGP finally completed
 *Celerais a subsidiary of which focuses on genetic sequencing and related
technologies

12. • James Watson
• Original Head of HGP
Francis Collins
Director of NIH
Craig Venter
Sequence Human Genome
ople of Human Genome Project

13. Brief History Of Human Genome
project
1984 to 1986 – first proposed at US DOE meetings
1988 – endorsed by US National Research Council
(Funded by NIH and US DOE $3 billion set aside)
1990 – Human Genome Project started (NHGRI)
Later – UK, US,France, Japan, Germany, China
1998. Celera announces a 3-year plan to complete the
project years early
First draft published in Science and Nature in February,
2001
Finished Human Genome sequence published in Nature
2003.

14. The Human Genome Project
- Timelines -
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
1st Human
Chromosome
Sequenced
Congress
Recommends
15 year HGP
Project
HGP
Officially
Begins
Low
Resolution
Linkage
Map of HG
Published
High Resolution
Maps of
Specific
Chromosomes
Announced
E.coli
Genome
Completed
Celera
Genomics
Formed
Conference
on HGP
Feasibility
S. cerevisiae
Genome
Completed
C. elegans
Genome
Completed
Fly
Genome
Completed
Human
Genome
Published
President announces
genome working
draft completed
Science (Feb. 16, 2001) - Celera
Nature (Feb. 15, 2001) - HGP

15. Human Genome Project
Goals
Identify all the approximate 30,000 genes in human DNA,
Determine the sequences of the 3 billion chemical base pairs that make up human
DNA
Store this information in databases,
 Improve tools for data analysis,
 Transfer related technologies to the private sector, and
 Address the ethical, legal, and social issues (ELSI) that may arise from the project.

16. The first reference genome is a composite
genome from several different people.
Generated from 10-20 primary samples taken
from numerous anonymous() donors across racial()
and ethnic() groups.

17. What does the draft human genome
sequence tell us?
By the Numbers
The human genome contains 3 billion chemical nucleotide bases (A, C, T,
and G).
The average gene consists of 3000 bases, but sizes vary greatly, with the
largest known human gene being dystrophin at 2.4 million bases.
 The total number of genes is estimated at around 30,000--much lower
than previous estimates of 80,000 to 140,000.
 Almost all (99.9%) nucleotide bases are exactly the same in all people.
 The functions are unknown for over 50% of discovered genes.
 Chromosome no. 1 has the most genes (2968), and the Y chromosome
has the fewest (231).

18. How It's Arranged
 The human genome's gene-dense "urban centers" are
predominantly composed of the DNA building blocks G and C.
 In contrast, the gene-poor "deserts" are rich in the DNA building
blocks A and T. GC- and AT-rich regions usually can be seen
through a microscope as light and dark bands on chromosomes.
 Genes appear to be concentrated in random areas along the
genome, with vast expanses of noncoding DNA between.

19.  Less than 2% of the genome codes for proteins.
 Repeated sequences that do not code for proteins ("junk DNA")
make up at least 50% of the human genome.
 Repetitive sequences are thought to have no direct functions, but
they shed light on chromosome structure and dynamics. Over time,
these repeats reshape the genome by rearranging it, creating entirely
new genes, and modifying and reshuffling existing genes.
 The human genome has a much greater portion (50%) of repeat
sequences than the mustard weed (11%)the worm (7%)and the fly
(3%).

20. How the Human Compares with Other
Organisms• Unlike the human's seemingly random distribution of gene-rich
areas, many other organisms' genomes are more uniform, with genes evenly spaced
throughout.
 Humans have on average three times as many kinds of proteins as the fly or worm
because of mRNA transcript "alternative splicing" and chemical modifications to the
proteins. This process can yield different protein products from the same gene.
 Humans share most of the same protein families with worms, flies, and plants; but
the number of gene family members has expanded in humans, especially in proteins
involved in development and immunity.
 Although humans appear to have stopped accumulating repeated DNA over 50
million years ago, there seems to be no such decline in rodents. This may account for
some of the fundamental differences between hominids and rodents( ), although gene
estimates are similar in these species. Scientists have proposed many theories to explain
evolutionary contrasts between humans and other organisms, including those of life
span, litter sizes, inbreeding, and genetic drift.

21. Variations and Mutations
Scientists have identified about 3 million locations where single-base
DNA differences (SNPs) occur in humans. This information promises to
revolutionize the processes of finding chromosomal locations for
disease-associated sequences and tracing human history.
The ratio of germline (sperm or egg cell) mutations is 2:1 in males vs
females. Researchers point to several reasons for the higher mutation
rate in the male germline, including the greater number of cell divisions
required for sperm formation than for eggs.

22. How does the human genome
stack up?
Organism Genome Size (Bases) Estimated Genes
Human (Homo sapiens) 3 billion 30,000
Laboratory mouse (M. musculus) 2.6 billion 30,000
Mustard weed (A. thaliana) 100 million 25,000
Roundworm (C. elegans) 97 million 19,000
Fruit fly (D. melanogaster) 137 million 13,000
Yeast (S. cerevisiae) 12.1 million 6,000
Bacterium (E. coli) 4.6 million 3,200
Human immunodeficiency virus (HIV) 9700 9

23. Medicine
Bioinformatics
Biotechnology
DNA chip
technology
Gene therapy
applications
Diagnostic &
therapeutic
applications
Medicine &
pharmaceutical industries
Agriculture &
Bioremediation
Industries
Microarray
Technology
Proteomics
Pharmacogenomics
Preventative
measures
Developmental
Biology
Evolutionary &
Comparative
Biologists
Benefits of Human Genome
Project

24.  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 post-translational events
 Interaction of proteins in complex molecular machines
 Predicted vs experimentally determined gene function
 Evolutionary conservation among organisms
 Protein conservation (structure and function)
 Proteomes (total protein content and function) in organisms
 Correlation of SNPs (single-base DNA variations among individuals) with health and
disease
 Disease-susceptibility prediction based on gene sequence variation
 Genes involved in complex traits and multigene diseases
 Complex systems biology including microbial consortia useful for environmental
restoration
 Developmental genetics, genomics
Future Challenges:
What We Still Don’t Know

25. Anticipated() Benefits of Genome
Research
Molecular Medicine
 Improve diagnosis of disease
 Create drugs based on molecular information
 Use gene therapy and control systems as drugs
 Design “custom drugs” (pharmacogenomics) based on individual genetic profiles
Microbial Genomics
 Rapidly detect and treat pathogens (disease-causing microbes) in clinical practice
 Develop new energy sources (biofuels)
 Donitor environments to detect pollutants
 Protect citizenry from biological and chemical warfare
 Clean up toxic waste safely and efficiently

26. Risk Assessment
 Evaluate the health risks faced by individuals who may be exposed to radiation
(including low levels in industrial areas) and to cancer-causing chemicals and
toxins
Bioarchaeology, Anthropology, Evolution,
and Human Migration
 Study evolution through germline mutations in lineages
Study migration of different population groups based on maternal inheritance
Study mutations on the Y chromosome to trace lineage and migration of males
Compare breakpoints in the evolution of mutations with ages of populations and
historical events

27. DNA Identification (Forensics)
Identify potential suspects whose DNA may match evidence left at crime scenes
Exonerate persons wrongly accused of crimes
Identify crime and catastrophe victims
Establish paternity and other family relationships
Identify endangered and protected species as an aid to wildlife officials (could
be used for prosecuting poachers)
Detect bacteria and other organisms that may pollute air, water, soil, and food
Match organ donors with recipients in transplant programs
Determine pedigree for seed or livestock breeds
Authenticate consumables such as caviar and wine

28. Agriculture, Livestock Breeding, and
Bioprocessing
 Grow disease-, insect-, and drought-resistant crops
Breed healthier, more productive, disease-resistant farm
animals
Grow more nutritious produce
Develop biopesticides
Incorporate edible vaccines incorporated into food products
Develop new environmental cleanup uses for plants like
tobacco

29. ELSI: 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 individual’s
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.

30. Uncertainties associated with gene tests for susceptibilities and complex
conditions (e.g., heart disease, diabetes, and Alzheimer’s disease).
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.

31. Beyond the HGP: What’s
Next?
HapMap Systems Biology
Exploring Microbial Genomes for
Energy and the Environment
Chart genetic variation
within the human genome

32. 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

33. 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

35. Map of Chromosome 16

36. Costs of Human Genomic Sequencing
 Clone by clone
 $0.30 per finished base
 $130 million per year for 7 years
 Total $900 million spent by end of 2003
 Shotgun
 $0.01 per raw base
 $130 million for 3 years would provide
 10× coverage/redundancy plus an additional $90
million for informatics

37. Human Genome Projects Progress

38. Human Chromosome
Map

39.  Contains over
3000 genes
 Contains over
240 million
base pairs, of
which ~90%
have been
determined
Chromosome #1

40.  Contains over
2500 genes
 Contains over
240 million
base pairs, of
which ~95%
have been
determined
Chromosome #2

41.  Contains
approximatel
y 1900 genes
 Contains
approximatel
y 200 million
base pairs, of
which ~95%
have been
determined
Chromosome# 3

42.  Contains
approximatel
y 1600 genes
 Contains
approximatel
y 190 million
base pairs, of
which ~95%
have been
determined
Chromosome #4

43.  Contains
approximatel
y 1700 genes
 Contains
approximatel
y 180 million
base pairs, of
which over
95% have
been
determined
Chromosome #5

44.  Contains
approximatel
y 1900 genes
 Contains
approximatel
y 170 million
base pairs, of
which over
95% have
been
determined
Chromosome #6

45.  Contains
approximatel
y 1800 genes
 Contains over
150 million
base pairs, of
which over
95% have
been
determined
Chromosome# 7

46.  Contains over
1400 genes
 Contains over
140 million
base pairs, of
which over
95% have
been
determined
Chromosome #8

47.  Contains over
1400 genes
 Contains over
130 million
base pairs, of
which over
85% have
been
determined
Chromosome# 9

48.  Contains over
1400 genes
 Contains over
130 million
base pairs, of
which over
95% have
been
determined
Chromosome# 10

49.  Contains
approximatel
y 2000 genes
 Contains over
130 million
base pairs, of
which over
95% have
been
determined
Chromosome# 11

50.  Contains over
1600 genes
 Contains over
130 million
base pairs, of
which over
95% have
been
determined
Chromosome# 12

51.  Contains
approximatel
y 800 genes
 Contains over
110 million
base pairs, of
which over
80% have
been
determined
Chromosome# 13

52.  Contains
approximatel
y 1200 genes
 Contains over
100 million
base pairs, of
which over
80% have
been
determined
Chromosome #14

53.  Contains
approximatel
y 1200 genes
 Contains
approximatel
y 100 million
base pairs, of
which over
80% have
been
determined
Chromosome# 15

54.  Contains
approximatel
y 1300 genes
 Contains
approximatel
y 90 million
base pairs, of
which over
85% have
been
determined
Chromosome #16

55.  Contains over
1600 genes
 Contains
approximatel
y 80 million
base pairs, of
which over
95% have
been
determined
Chromosome# 17

56.  Contains over
600 genes
 Contains over
70 million
base pairs, of
which over
95% have
been
determined
Chromosome #18

57.  Contains
over 1700
genes
 Contains
over 60
million base
pairs, of
which over
85% have
been
determined
Chromosome# 19

58.  Contains over
900 genes
 Contains over
60 million
base pairs, of
which over
90% have
been
determined
Chromosome #20

59.  Contains over
400 genes
 Contains over
40 million
base pairs, of
which over
70% have
been
determined
Chromosome# 21

60.  Contains over
800 genes
 Contains over
40 million
base pairs, of
which
approximately
70% have
been
determined
Chromosome# 22

61. • Contains over
1400 genes
• Contains over
150 million
base pairs, of
which
approximately
95% have
been
determined
X Chromosome

62.  Contains over
200 genes
 Contains over
50 million
base pairs, of
which
approximatel
y 50% have
been
determined
Y Chromosome
http://www.ncbi.nlm.nih.gov/books/NBK22
266/#A273
National Center for Biotechnology
Information (US)

64. Refrences
 http://www.bioperl.org/GetStarted/tpj_ls_bio.html
 Lincoln Stein’s classic article on “How Perl Saved The
Human Genome Project”
 http://www.eecs.berkeley.edu/~gene/Papers/greedy.pat
h.merging.pdf
 Celera Assembler Algorithm
 http://doegenomes.org
 http://www-
management.wharton.upenn.edu/pennings/coursedocuments/e
xecutive_education_courses/557/genome%20Paper%201.doc
 http://www.ornl.gov/sci/techresources/Human_Genome
/education/images.shtml