THE HUMAN GENOME PROJECT

SUBMITTED TO: Ma’am HINA

SUBMITTED BY: ZUNAIRA RAFIQ

ROLL NO:39
SESSION:2015-2019
Contents
The Human Genome Project ................................................................................. 3
History ................................................................................................................... 4
Objectives: ............................................................................................................ 7
Impact: .................................................................................................................. 8
State of completion:.............................................................................................. 8
Applications and proposed benefits: .................................................................... 9
Genome donors:.................................................................................................. 14
Ethical, legal and social issue: ............................................................................. 15
 All our genes are collectively referred to as genome. In other words, genome
is the entire genetic information, complement and all of the hereditary material
possessed by an organism. It can be further explained as living creature’s genetic
material which contains the hereditary instructions for constructing, operating, and
maintaining an organism, and transferring life on to the next generation.

The Human Genome Project

The Human Genome Project (HGP) was a collaborative scientific research
program on international scale conducted to discover all the chemical base pairs
which make up human DNA for further biological studies. Specifically, its primary
goal was to map and identify both physically and functionally, the approximately
20,000–25,000 genes of the human genome. The HGP was going to offer different
research perspectives by revealing the genetic factors in human diseases, to help
establish new strategies for their diagnosis, cure and prevention.
Although, the Human Genome Project mainly focused on understanding the
genetic makeup of the human species, the project also included parallel studies on
some selected nonhuman organisms such as E. coli (bacterium), the laboratory
mouse and the fruit fly. This intensive public effort can be considered as the largest
single research projects in modern science.

In 1990, the U.S Department of Energy and the National Institutes of Health
(NIH) joined with international partners in an expedition to sequence all 3 billion
chemical base pairs in the human genome which is the complete set of DNA in the
human body. Originally, the project was organized to last 15 years but due to rapid
technological advancements, it was completed in spring 2003 thus coinciding with
the 50th anniversary of Watson and Crick's model of the basic structure of DNA.

It is believed that the mapping of human genes has marked the beginning of
the ‘biology century’, during which the fields of medicine and health care are going
to flourish immensely.

History
The Human Genome Project was a 15-year-long, publicly funded project
initiated in 1990 with the objective of determining the DNA sequence of the entire
euchromatic human genome within 15 years In May 1985, Robert Sinsheimer
organized a workshop to discuss sequencing the human genome, but for a number
of reasons the NIH was uninterested in pursuing the proposal.

The following March, the Santa Fe Workshop was organized by Charles

DeLisi and David Smith of the Department of Energy's Office of Health and
Environmental Research (OHER). At the same time Renato Dulbecco proposed
whole genome sequencing in an essay in Scienc. James Watson followed two
months later with a workshop held at the Cold Spring Harbor Laboratory.
The fact that the Santa Fe workshop was motivated and supported by a
Federal Agency opened a path, albeit a difficult and tortuous one, for converting
the idea into a public policy in the United States. In a memo to the Assistant
Secretary for Energy Research (Alvin Trivelpiece), Charles DeLisi, who was then
Director of the OHER, outlined a broad plan for the project.

This started a long and complex chain of events which led to approved
reprogramming of funds that enabled the OHER to launch the Project in 1986, and
to recommend the first line item for the HGP, which was in President Reagan's 1988
budget submission and ultimately approved by the Congress.

Of particular importance in Congressional approval was the advocacy of

Senator Peter Domenici, whom DeLisi had befriended.[11] Domenici chaired the
Senate Committee on Energy and Natural Resources, as well as the Budget
Committee, both of which were key in the DOE budget process. Congress added a
comparable amount to the NIH budget, thereby beginning official funding by both
agencies.

Alvin Trivelpiece sought and obtained the approval of DeLisi's proposal by

Deputy Secretary William Flynn Martin. This chart was used in the spring of 1986
by Trivelpiece, then Director of the Office of Energy Research in the Department of
Energy, to brief Martin and Under Secretary Joseph Salgado regarding his intention
to reprogram $4 million to initiate the project with the approval of Secretary
Herrington. This reprogramming was followed by a line item budget of $16 million
in the Reagan Administration 1987 budget submission to Congress. It subsequently
passed both Houses. The Project was planned for 15 years.

Candidate technologies were already being considered for the proposed

undertaking at least as early as 1985.[15] In 1990, the two major funding agencies,
DOE and NIH, developed a memorandum of understanding in order to coordinate
plans and set the clock for the initiation of the Project to 1990. At that time, David
Galas was Director of the renamed “Office of Biological and Environmental
Research” in the U.S. Department of Energy's Office of Science and James Watson
headed the NIH Genome Program.

In 1993, Aristides Patrinos succeeded Galas and Francis Collins succeeded

James Watson, assuming the role of overall Project Head as Director of the U.S.
National Institutes of Health (NIH) National Center for Human Genome Research
(which would later become the National Human Genome Research Institute). A
working draft of the genome was announced in 2000 and the papers describing it
were published in February 2001. A more complete draft was published in 2003,
and genome "finishing" work continued for more than a decade.

The $3-billion project was formally founded in 1990 by the US Department

of Energy and the National Institutes of Health, and was expected to take 15 years.
In addition to the United States, the international consortium comprised geneticists
in the United Kingdom, France, Australia, China and myriad other spontaneous
relationships. Considering the inflation, the project roughly costed $5 billion.

Due to widespread international cooperation and advances in the field of

genomics (especially in sequence analysis), as well as major advances in computing
technology, a 'rough draft' of the genome was finished in 2000 (announced jointly
by U.S. President Bill Clinton and the British Prime Minister Tony Blair on June 26,
2000). This first available rough draft assembly of the genome was completed by
the Genome Bioinformatics Group at the University of California, Santa Cruz,
primarily led by then graduate student Jim Kent.

Ongoing sequencing led to the announcement of the essentially complete

genome on April 14, 2003, two years earlier than planned. In May 2006, another
milestone was passed on the way to completion of the project, when the sequence
of the last chromosome was published in Nature. The institutions, companies and
laboratories in Human Genome Program are listed below, according to NIH.

Objectives:
Human Genome Project had the following objectives:
 1. To identify all the approximately 20,000-25,000 genes in human DNA
2. To determine the sequences of the 3 billion chemical base pairs that make
up human DNA
3. To store this information in databases
4. To improve tools for data analysis
5. To transfer related technologies to the private sector
6. To address the ethical, legal, and social issues (ELSI) that may arise from the
project.

Impact:
The Human Genome Project played a vital role in establishing U.S. as the global
leader in the new biotechnology sector by stirring advancement in biotechnology
innovation worldwide. The significance of HGP can be highlighted through the
following points:
1. It has aided the discovery of more than 1,800 disease genes.
2. It enabled researchers to find a gene suspected of causing an inherited
disease quickly.
3. It paved the way for more than 1,000 genetic tests for various human
diseases/conditions.
4. It resulted in developing 350 biotechnology-based products.
5. It laid foundation for the development of the HapMap in 2005 which is a
catalog of common genetic variation or haplotypes in the human genome.
6. It is worth mentioning that the mankind will continue to reap the benefits of
the Human Genome Project for long period of coming time.

State of completion:
 The project was not able to sequence all the DNA found in human cells. It
sequenced only euchromatic regions of the genome, which make up 92% of the
human genome. The other regions, called heterochromatic, are found in
centromeres and telomeres, and were not sequenced under the project.

The Human Genome Project (HGP) was declared complete in April 2003. An
initial rough draft of the human genome was available in June 2000 and by February
2001 a working draft had been completed and published followed by the final
sequencing mapping of the human genome on April 14, 2003. Although this was
reported to cover 99% of the euchromatic human genome with 99.99% accuracy,
a major quality assessment of the human genome sequence was published on May
27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which was
within the intended goal. Further analyses and papers on the HGP continue to
occur.

In March 2009, the Genome Reference Consortium (GRC) released a more

accurate version of the human genome, but that still left more than 300 gaps.[28]
In October 2018, the GRC still indicated 514 gaps, most of which are annotated as
"stalled" or "under investigation/review", so it seems they will not be resolved any
time soon.

Applications and proposed benefits:

The sequencing of the human genome holds benefits for many fields, from
molecular medicine to human evolution. The Human Genome Project, through its
sequencing of the DNA, can help us understand diseases including: genotyping of
specific viruses to direct appropriate treatment; identification of mutations linked
to different forms of cancer; the design of medication and more accurate prediction
of their effects; advancement in forensic applied sciences; biofuels and other
energy applications; agriculture, animal husbandry, bioprocessing; risk assessment;
bioarcheology, anthropology and evolution. Another proposed benefit is the
commercial development of genomics research related to DNA based products, a
multibillion-dollar industry.

The sequence of the DNA is stored in databases available to anyone on the

Internet. The U.S. National Center for Biotechnology Information (and sister
organizations in Europe and Japan) house the gene sequence in a database known
as GenBank, along with sequences of known and hypothetical genes and proteins.
Other organizations, such as the UCSC Genome Browser at the University of
California, Santa Cruz, and Ens .present additional data and annotation and
powerful tools for visualizing and searching it.

Computer programs have been developed to analyze the data, because the
data itself is difficult to interpret without such programs. Generally speaking,
advances in genome sequencing technology have followed Moore's Law, a concept
from computer science which states that integrated circuits can increase in
complexity at an exponential rate. This means that the speeds at which whole
genomes can be sequenced can increase at a similar rate, as was seen during the
development of the above-mentioned Human Genome Project..

Some of the important techniques used in the human genome project are
as follow:

(а) DNA Sequencing are the sequencing methods for determining the order
of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule
of DNA. There are two common methods namely Maxam Gilbert technique which
uses chemicals to cleave DNA into fragments at specific bases; or, most commonly,
the Sanger technique.

It is also called the di-deoxy or chain-terminating method. It uses DNA polymerase

to make new DNA chains, in the presence of di- deoxynucleotides chain terminators
to stop the chain randomly as it grows. In both cases, the DNA fragments are
separated according to length by polyacrylamide gel electrophoresis. This enables
the sequence to be read directly from the gel.

(b) Employment of Restriction Fragment-Length Polymorphisms (RFLP).

 (c) Yeast Artificial Chromosomes (YAC) is a vector (carrier) created and used
in the laboratory to clone pieces of DNA. A YAC is constructed from the telomeric,
centromeric, and replication origin sequences needed for replication in yeast cells.
The telomere is the end of the chromosome; the centromere is the chromosome
region to which spindle fibers attach during cell division; and the replication origin
sequences are the spots where the replication of DNA starts.
Genome donors:
In the IHGSC international public-sector HGP, researchers collected blood
(female) or sperm (male) samples from a large number of donors. Only a few of
many collected samples were processed as DNA resources. Thus the donor
identities were protected so neither donors nor scientists could know whose DNA
was sequenced. DNA clones from many different libraries were used in the overall
project, with most of those libraries being created by Pieter J. de Jong's. Much of
the sequence (>70%) of the reference genome produced by the public HGP came
from a single anonymous male donor from Buffalo, New York (code name
RP11).[49][50]

HGP scientists used white blood cells from the blood of two male and two
female donors (randomly selected from 20 of each) – each donor yielding a
separate DNA library. One of these libraries (RP11) was used considerably more
than others, due to quality considerations. One minor technical issue is that male
samples contain just over half as much DNA from the sex chromosomes (one X
chromosome and one Y chromosome) compared to female samples (which contain
two X chromosomes). The other 22 chromosomes (the autosomes) are the same
for both sexes.

Although the main sequencing phase of the HGP has been completed,
studies of DNA variation continued in the International HapMap Project, whose
goal was to identify patterns of single-nucleotide polymorphism (SNP) groups
(called haplotypes, or “haps”). The DNA samples for the HapMap came from a total
of 270 individuals: Yoruba people in Ibadan, Nigeria; Japanese people in Tokyo; Han
Chinese in Beijing; and the French Centre d’Etude du Polymorphisme Humain
(CEPH) resource, which consisted of residents of the United States having ancestry
from Western and Northern Europe.
 In the Celera Genomics private-sector project, DNA from five different
individuals were used for sequencing. The lead scientist of Celera Genomics at that
time, Craig Venter, later acknowledged (in a public letter to the journal Science)
that his DNA was one of 21 samples in the pool, five of which were selected for use.
In 2007, a team led by Jonathan Rothberg published James Watson's entire
genome, unveiling the six-billion-nucleotide genome of a single individual for the
first time.

Ethical, legal and social issue:

At the onset of the Human Genome Project several ethical, legal, and social
concerns were raised in regards to how increased knowledge of the human genome
could be used to discriminate against people. One of the main concerns of most
individuals was the fear that both employers and health insurance companies
would refuse to hire individuals or refuse to provide insurance to people because
of a health concern indicated by someone's genes.

In 1996 the United States passed the Health Insurance Portability and
Accountability Act (HIPAA) which protects against the unauthorized and non-
consensual release of individually identifiable health information to any entity not
actively engaged in the provision of healthcare services to a patient.[59] Other
nations passed no such protections.

Along with identifying all of the approximately 20,000–25,000 genes in the

human genome, the Human Genome Project also sought to address the ethical,
legal, and social issues that were created by the onset of the project. For that the
Ethical, Legal, and Social Implications (ELSI) program was founded in 1990. Five
percent of the annual budget was allocated to address the ELSI arising from the
project.[17][60] This budget started at approximately $1.57 million in the year
1990, but increased to approximately $18 million in the year 2014.[61]
 Whilst the project may offer significant benefits to medicine and scientific
research, some authors have emphasized the need to address the potential social
consequences of mapping the human genome. "Molecularising disease and their
possible cure will have a profound impact on what patients expect from medical
help and the new generation of doctors' perception of illness."
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