Human Genome Project (HGP) was an international  scientific research  project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the  genes  of the human genome  from both a physical and a functional

1. HUMAN GENOME PROJECT
THE LIFE’S CODE
CRACKING DOWN
Saba Hayat
MPHIL ZOOLOGY

2. The Human Genome Project (HGP) was an international scientific
research project with the goal of determining the base pairs that make up human
DNA, and of identifying and mapping all of the genes of the human genome from
both a physical and a functional
• formally begun in October 1990 and completed in 2003.
• to discover all the estimated 20,000 to 25,000 human genes and make them
accessible for further biological study.

3. Time line of Human Genome Project
1970
Fredrick Sanger developed a technique for DNA sequencing, known as the Sanger’s
method of DNA sequencing
1985
Robert Sinsheimer at UCSC proposed the idea of sequencing the human genome.
1986
The U.S. Dept of Energy and the National Institute of Health came forward to fund
the Human Genome Project.

4. 1990
HGP was officially launched with James Watson as its Project Director. the 1ST
gene to be mapped was BRCA1, which is the gene for breast cancer.
1993
1st 5 year plan for HGP published. Sanger Institute(UK) joins HGP.
1994
HGP’s Human genetic mapping goal was achieved.
1995
Genetic privacy act was passed. 1st bacterial genome was sequenced (Hemophilus
influenzae)

5. 1st Human
Gene map was
published.
Yeast genome
was
sequenced.
HGP’s mouse
genetic
mapping goal
was achieved
1997
• NIH becomes
NHGRI
• E.coli genome
sequenced.

6. 1998
• 2nd 5 year plan for HGP was published.
• Japan’s RIKEN Genomic Services Centre was established..
1999
• sequencing of human chromosome 22 was completed and was
published in “The Nature.”

7. 2000
working draft of human genome completed
US president Clinton & UK’s PM Blair support free access
to genome information
2001
working draft of human genome sequence was published in
“The Nature” & “Science”.

8. 2002
• working draft of mouse genome
sequence was completed &
published.
2003
• finished version of human genome
sequence was completed.
• HGP ended with all the goals
achieved.
CLINTON IN conference for HGP
Celebrating 10th Anniversary .

9. Celera is a subsidiary of Quest Diagnostics which focuses on
genetic sequencing and related technologies.
founded in 1998 as a business unit of Applera
finally acquired by Quest Diagnostics in 2011
• Venter believed that shotgun sequencing was most
effective way to get useful human genome data.
It was rejected by the Human Genome Project however. John Craig Venter
• he sought funding from the private sector to birth Celera
Genomics

10. Genomes sequenced by Celera Genomics
Eukaryotes:
Drosophila melanogaster (fruit fly)
Human, specifically mostly that of Craig Venter
Anopheles gambiae (mosquito)
Mouse
Prokaryotes:
Haemophilus influenzae

11. The first printout of the human genome to be presented as a series of books, displayed at the Welcome Collection,
London
Russ London at English Wikipedia
The first printout of the human genome to be presented as a series of books, displayed in the 'Medicine Now' room at
the Wellcome Collection, London. The 3.4 billion units of DNA code are transcribed into more than a hundred
volumes, each a thousand pages long, in type so small as to be barely legible.

12. Sequencing techniques used in HGP are
Shotgun sequencing method
• Shotgun sequencing is a laboratory technique for determining the DNA sequence
of an organism's genome.
• involves breaking the genome into a collection of small DNA fragments, then
sequenced individually.
• A computer program looks for overlaps in the DNA sequences and uses them to
place the individual fragments in their correct order to reconstitute the genome

14. Sanger sequencing method
• dideoxy method, Sanger sequencing involves using a purified DNA
polymerase enzyme to synthesize DNA chains of varying lengths
• reaction mixture is the inclusion of dideoxynucleotide triphosphates (ddNTPs).
• when a ddNTPs is incorporated into the growing strand, it inhibits further strand
extension.

15. • The result of many of these reactions is a number of DNA fragments of varying
length.
• These are separated by size using gel
• This procedure is sensitive enough
to distinguish DNA fragments that differ in size by only a single nucleotide.

17. DNA cloning vectors
• Before large DNA molecules can be sequenced,
• they are cut into small pieces and multiplied, or cloned,
• into numerous copies using microbial-based "cloning" vectors.
• Today, the bacterial artificial chromosome (BAC) is the most
commonly used vector for initial DNA amplification before
sequencing.

18. Outcomes of HGP
Gene number and density
• In the latest assembly of the human genome (Build 36), which covers a total of
3 253 037 807 base pairs, 23 686 known and novel protein‐coding genes have
been annotated
• Gene density varies between the human chromosomes, allowing one to
distinguish gene‐rich and gene‐poor chromosomes. The gene distribution within
chromosomes is also rather uneven.
• gene‐poor regions have been identified; these are regions that are devoid of
protein‐coding genes over distances of several megabases but may nevertheless

19. Nonprotein‐coding RNAs and transcripts of unknown function
• analysis have revealed that, in addition to protein‐coding genes, several thousand
RNA genes are present.
• Nonprotein‐coding RNAs of known function include not only structural RNAs
such as tRNAs, rRNAs and small nuclear RNAs
• but also regulatory RNAs (mRNAs & siRNAs)
• which are involved in the sequence‐specific transcriptional and
posttranscriptional modulation of gene expression

20. Sequence elements controlling gene expression
The comparison of the human genome sequence with the orthologous sequences
of mouse and rat revealed the existence of 481 Ultraconserved elements (UCEs)
of at least 200 bp
This strongly supports the functionality of these UCEs, which may represent
long‐range enhancers of gene expression.

21. Genetic diversity of the human genome
• more than 1.4 million single nucleotide polymorphisms (SNPs) were
identified in the human genome
• This number exploited by the Human Haplotype Map (HapMap) project with
the aim of developing methods for the design and analysis of genome‐wide
association studies to map phenotypic variation in humans (International
HapMap Consortium, 2005).

22. Reconstruction of ancestral mammalian/eutherian genomes
• Together with other techniques such as comparative chromosome painting,
these sequence comparisons have the potential to
• provide new insights into the evolutionary interrelationship of the different
eutherian orders
• within the mammalian phylogenetic tree

23. Some current and potential applications of genome research include
1. Molecular medicine
2. Energy sources and environmental applications
3. Risk assessment
4. Bio archaeology, anthropology, evolution, and human migration
5. DNA forensics (identification)
6. Agriculture, livestock breeding, and bioprocessing

24. Molecular Medicine
•Improved diagnosis of disease
•Earlier detection of genetic predispositions to disease
•Rational drug design
•Gene therapy and control systems for drugs
•Pharmacogenomics "custom drugs
genome maps have aided researchers seeking genes associated with dozens of
genetic conditions, including myotonic dystrophy, fragile X syndrome,
neurofibromatosis types 1 and 2, inherited colon cancer, Alzheimer's
disease, and familial breast cancer.

25. Energy and Environmental Applications
•Use microbial genomics research to create new energy sources (biofuels)
•Use microbial genomics research to develop environmental monitoring
techniques to detect pollutants
•Use microbial genomics research for safe, efficient environmental
remediation
•Use microbial genomics research for carbon sequestration

26. Risk Assessment
•Assess health damage and risks caused by radiation exposure, including low-dose
exposures
•Assess health damage and risks caused by exposure to mutagenic chemicals and
cancer-causing toxins
•Reduce the likelihood of heritable mutations
DNA Forensics (Identification)
•Identify potential suspects whose DNA may match evidence left at crime scenes
•Exonerate persons wrongly accused of crimes
•Identify crime and catastrophe victims

27. •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
•Establish paternity and other family relationships

29. Outcomes of HGP
 There are approximately 22,300 protein-coding genes in human beings, the same
range as in other mammals. Mouse – 23,000 genes (approx.)
 Drosophila – 17,000 genes (approx.), C.elegans - < 22,000 genes
 We share many homologous genes called "orthologs" with both these animals.
 But:-
 Many of our protein-encoding genes produce more than one protein product (e.g.,
by alternative splicing of the primary transcript of the gene).
 On average, each of our ORFs produces 2 to 3 different proteins.
 So the human "proteome" (our total number of proteins) may be 10 or more times

30.  The combinatorial use of these elements provides much greater flexibility of
gene expression than is found in Drosophila and C.elegans.
 Humans, and presumably most vertebrates, have genes not found in
invertebrate animals like Drosophila and C. elegans.
 Few of those genes are: antibodies and T cell receptors for antigen (TCRs) the
transplantation antigens of the major histocompatibility complex (MHC) &
human leucocyte antigen (HLA).

31. Area Goal Achieved Date
Genetic Map
2- to 5-cMresolution
map (600 - 1,500
markers)
1-cM resolution
map(3,000 markers)
September 1994
Physical Map 30,000 STSs 52,000 STSs October 1998
DNA Sequence
95% of gene-containing
part of human sequence
finished to 99.99%
accuracy
99% of gene-containing
part
of human sequence
finished to 99.99%
accuracy
April 2003
Capacity and Cost
of Finished
Sequence
Sequence 500 Mb/year
at < $0.25 per finished
base
Sequence
>1,400Mb/year at
<$0.09 per finished base
November 2002
Human Sequence
Variation
100,000 mapped human
SNPs
3.7 million mapped
human SNPs
February 2003

32. Gene Identification Full-length human cDNAs
15,000 full-lengthhuman
cDNAs
March 2003
Model Organisms
Complete genome sequences
of E. coli, S .cerevisiae, C.
elegans, D. melanogaster
Finished genome sequences
of E. coli, S. cerevisiae, C.
elegans, D. melanogaster, plus
whole-genome drafts of several
others, including C. briggsae, D.
pseudoobscura, mouse and rat
April 2003
Functional Analysis
Develop genomic-scale
technologies
High-throughput
oligonucleotide synthesis DNA
microarrays
Eukaryotic, whole-genome
knockouts (yeast)
Scale-up of two-hybrid system
for protein-protein interaction
1994
1996
1999
2002

33. How much did it cost?
In 1990, Congress set a target completion date of 2005. estimates
cost was a total of $3 billion over this period, the project ended up costing less than
expected,
about $2.7 billion in FY 1991 dollars.
Additionally, the project was completed more than two years ahead of schedule.

34. The human genome project (ethical, legal and social issues)
The DOE and the NIH devoted 3% to 5% of their annual HGP budgets toward
studying the (ELSI) surrounding availability of genetic information
• Privacy and confidentiality of genetic information.
• Fairness in the use of genetic information
• Psychological impact, stigmatization, and discrimination
• Reproductive issues
• Clinical issues
• Conceptual and philosophical implications
• Health and environmental issues