The Human Genome Project (HGP) is a project to de-code (i.e. sequence) more
than 3 billion nucleotides contained in a haploid reference human genome and to
identify all the genes present in it. The reference human genome sequence was
considered pragmatically 'complete' at 92% in 2005 in publications by an
international public HGP and somewhat independently by a private company Celera
Genomics. Recently, several groups have announced efforts to extend this to
diploid human genomes including the International HapMap Project, Applied
Biosystems, Perlegen, Illumina, JCVI, Personal Genome Project, and Roche-454.
The "genome" of any given individual (except for identical twins and cloned
animals) is unique; mapping "the human genome" involves sequencing multiple
variations of each gene. The project did not study all of the DNA found in human
cells; some heterochromatic areas (about 8% of the total) remain unsequenced.
The project began in 1990 initially headed by James D. Watson at the U.S.
National Institutes of Health. A working draft of the genome was released in
2000 and a complete one in 2003, with further analysis still being published. A
parallel project was conducted by the private company Celera Genomics. Most of
the sequencing was performed in universities and research centers from the
United States, Canada and Britain. The mapping of human genes is an important
step in the development of medicines and other aspects of health care.
While the objective of the Human Genome Project is to understand the genetic
makeup of the human species, the project also has focused on several other
nonhuman organisms such as E. coli, the fruit fly, and the laboratory mouse. It
remains one of the largest single investigational projects in modern science. .
The HGP originally aimed to map the nucleotides contained in a haploid reference
human genome (more than three billion). Several groups have announced efforts to
extend this to diploid human genomes including the International HapMap Project,
Applied Biosystems, Perlegen, Illumina, JCVI, Personal Genome Project, and
The "genome" of any given individual (except for identical twins and cloned
animals) is unique; mapping "the human genome" involves sequencing multiple
variations of each gene. The project did not study the entire DNA found in human
cells; some heterochromatic areas (about 8% of the total) remain un-sequenced.
Initiation of the Project was the culmination of several years of work supported
by the United States Department of Energy, in particular workshops in 1984 and
1986 and a subsequent initiative of the US Department of Energy. This 1987
report stated boldly, "The ultimate goal of this initiative is to understand the
human genome" and "knowledge of the human genome is as necessary to the
continuing progress of medicine and other health sciences as knowledge of human
anatomy has been for the present state of medicine." Candidate technologies were
already being considered for the proposed undertaking at least as early as 1985.
James D. Watson was head of the National Center for Human Genome Research at the
National Institutes of Health (NIH) in the United States starting from 1988.
Largely due to his disagreement with his boss, Bernadine Healy, over the issue
of patenting genes, he was forced to resign in 1992. He was replaced by Francis
Collins in April 1993, and the name of the Center was changed to the National
Human Genome Research Institute (NHGRI) in 1997.
The $3-billion project was formally founded in 1990 by the United States
Department of Energy and the U.S. National Institutes of Health, and was
expected to take 15 years. In addition to the United States, the international
consortium comprised geneticists in China, France, Germany, Japan, and the
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 then US president Bill Clinton and British Prime Minister
Tony Blair on June 26, 2000). Ongoing sequencing led to the announcement of the
essentially complete genome in April 2003, 2 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 the journal Nature.
State of completion
There are multiple definitions of the "complete sequence of the human genome".
According to some of these definitions, the genome has already been completely
sequenced, and according to other definitions, the genome has yet to be
completely sequenced. There have been multiple popular press articles reporting
that the genome was "complete." The genome has been completely sequenced using
the definition employed by the International Human Genome Project. A graphical
history of the human genome project shows that most of the human genome was
complete by the end of 2003. However, there are a number of regions of the human
genome that can be considered unfinished:
* First, the central regions of each chromosome, known as centromeres, are
highly repetitive DNA sequences that are difficult to sequence using current
technology. The centromeres are millions (possibly tens of millions) of base
pairs long, and for the most part these are entirely un-sequenced.
* Second, the ends of the chromosomes, called telomeres, are also highly
repetitive, and for most of the 46 chromosome ends these too are incomplete. It
is not known precisely how much sequence remains before the telomeres of each
chromosome are reached, but as with the centromeres, current technological
restraints are prohibitive.
* Third, there are several loci in each individual's genome that contain members
of multigene families that are difficult to disentangle with shotgun sequencing
methods - these multigene families often encode proteins important for immune
* Other than these regions, there remain a few dozen gaps scattered around the
genome, some of them rather large, but there is hope that all these will be
closed in the next couple of years.
In summary: the best estimates of total genome size indicate that about 92% of
the genome has been completed and it is likely that the centromeres and
telomeres will remain un-sequenced until new technology is developed that
facilitates their sequencing. Most of the remaining DNA is highly repetitive and
unlikely to contain genes, but it cannot be truly known until it is entirely
sequenced. Understanding the functions of all the genes and their regulation is
far from complete. The roles of junk DNA, the evolution of the genome, the
differences between individuals, and many other questions are still the subject
of intense interest by laboratories all over the world.
The sequence of the human 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 University of California, Santa Cruz , and
Ensembl 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 themselves are difficult to interpret without such
The process of identifying the boundaries between genes and other features in
raw DNA sequence is called genome annotation and is the domain of
bioinformatics. While expert biologists make the best annotators, their work
proceeds slowly, and computer programs are increasingly used to meet the
high-throughput demands of genome sequencing projects. The best current
technologies for annotation make use of statistical models that take advantage
of parallels between DNA sequences and human language, using concepts from
computer science such as formal grammars.
Another, often overlooked, goal of the HGP is the study of its ethical, legal,
and social implications. It is important to research these issues and find the
most appropriate solutions before they become large dilemmas whose effect will
manifest in the form of major political concerns.
All humans have unique gene sequences. Therefore the data published by the HGP
does not represent the exact sequence of each and every individual's genome. It
is the combined genome of a small number of anonymous donors. The HGP genome is
a scaffold for future work in identifying differences among individuals. Most of
the current effort in identifying differences among individuals involves single
nucleotide polymorphisms and the HapMap.
Almost all the goals that the Human Genome Project has set for itself have been
completed earlier than predicted. The Human Genome Project actually exceeded the
projected finishing time by two years. The Human Genome Project set a
reasonable, attainable goal of 95% of DNA to be sequenced. Not only did the
researchers surpass that goal, they shattered their prediction, and were able to
sequence 99.99% of a human's DNA. Not only did The Human Genome Project exceed
all goals and standards, it still continues making progress on those goals
How it was accomplished
Funding came from the US government through the National Institutes of Health in
the United States, and the UK charity, the Wellcome Trust, who funded the Sanger
Institute (then the Sanger Centre) in Great Britain, as well as numerous other
groups from around the world. The genome was broken into smaller pieces;
approximately 150,000 base pairs in length. These pieces were then spliced into
a type of vector known as "bacterial artificial chromosomes", or BACs, which are
derived from bacterial chromosomes which have been genetically engineered. The
vectors containing the genes can be inserted into bacteria where they are copied
by the bacterial DNA replication machinery. Each of these pieces was then
sequenced separately as a small "shotgun" project and then assembled. The
larger, 150,000 base pairs go together to create chromosomes. This is known as
the "hierarchical shotgun" approach, because the genome is first broken into
relatively large chunks, which are then mapped to chromosomes before being
selected for sequencing.
The public vs private approaches
In 1998, a similar, privately funded quest was launched by the American
researcher Craig Venter, and his firm Celera Genomics. Venter was a scientist at
the NIH during the early 1990s when the project was initiated. The $300 million
Celera effort was intended to proceed at a faster pace and at a fraction of the
cost of the roughly $3 billion publicly funded project.
Celera used a riskier technique called whole genome shotgun sequencing, which
had been used to sequence bacterial genomes of up to six million base pairs in
length, but not for anything nearly as large as the three billion base pair
Celera initially announced that it would seek patent protection on "only
200-300" genes, but later amended this to seeking "intellectual property
protection" on "fully-characterized important structures" amounting to 100-300
targets. The firm eventually filed preliminary ("place-holder") patent
applications on 6,500 whole or partial genes. Celera also promised to publish
their findings in accordance with the terms of the 1996 "Bermuda Statement," by
releasing new data quarterly (the HGP released its new data daily), although,
unlike the publicly funded project, they would not permit free redistribution or
commercial use of the data.
In March 2000, President Clinton announced that the genome sequence could not be
patented, and should be made freely available to all researchers. The statement
sent Celera's stock plummeting and dragged down the biotechnology-heavy Nasdaq.
The biotechnology sector lost about $50 billion in market capitalization in two
Although the working draft was announced in June 2000, it was not until February
2001 that Celera and the HGP scientists published details of their drafts.
Special issues of Nature (which published the publicly funded project's
scientific paper) and Science (which published Celera's paper ) described the
methods used to produce the draft sequence and offered analysis of the sequence.
These drafts covered about 83% of the genome (90% of the euchromatic regions
with 150,000 gaps and the order and orientation of many segments not yet
established). In February 2001, at the time of the joint publications, press
releases announced that the project had been completed by both groups. Improved
drafts were announced in 2003 and 2005, filling in to ~92% of the sequence
The competition proved to be very good for the project, spurring the public
groups to modify their strategy in order to accelerate progress. The rivals
initially agreed to pool their data, but the agreement fell apart when Celera
refused to deposit its data in the unrestricted public database GenBank. Celera
had incorporated the public data into their genome, but forbade the public
effort to use Celera data.
HGP is the most well known of many international genome projects aimed at
sequencing the DNA of a specific organism. While the human DNA sequence offers
the most tangible benefits, important developments in biology and medicine are
predicted as a result of the sequencing of model organisms, including mice,
fruit flies, zebrafish, yeast, nematodes, plants, and many microbial organisms
In 2004, researchers from the International Human Genome Sequencing Consortium
(IHGSC) of the HGP announced a new estimate of 20,000 to 25,000 genes in the
human genome. Previously 30,000 to 40,000 had been predicted, while estimates at
the start of the project reached up to as high as 2,000,000. The number
continues to fluctuate and it is now expected that it will take many years to
agree on a precise value for the number of genes in the human genome.
For more details on this topic, see History of genetics.
In 1976, the genome of the virus Bacteriophage MS2 was the first complete genome
to be determined, by Walter Fiers and his team at the University of Ghent
(Ghent, Belgium). The idea for the shotgun technique came from the use of an
algorithm that combined sequence information from many small fragments of DNA to
reconstruct a genome. This technique was pioneered by Frederick Sanger to
sequence the genome of the Phage Φ-X174, a virus that primarily infects bacteria
(bacteriophage) that was the first fully sequenced genome (DNA-sequence) in
1977. The technique was called shotgun sequencing because the genome was broken
into millions of pieces as if it had been blasted with a shotgun. In order to
scale up the method, both the sequencing and genome assembly had to be
automated, as they were in the 1980s.
Those techniques were shown applicable to sequencing of the first free-living
bacterial genome (1.8 million base pairs) of Haemophilus influenzae in 1995 and
the first animal genome (~100 Mbp) It involved the use of automated sequencers,
longer individual sequences using approximately 500 base pairs at that time.
Paired sequences separated by a fixed distance of around 2000 base pairs which
were critical elements enabling the development of the first genome assembly
programs for reconstruction of large regions of genomes (aka 'contigs').
Three years later, in 1998, the announcement by the newly-formed Celera Genomics
that it would scale up the shotgun sequencing method to the human genome was
greeted with skepticism in some circles. The shotgun technique breaks the DNA
into fragments of various sizes, ranging from 2,000 to 300,000 base pairs in
length, forming what is called a DNA "library". Using an automated DNA sequencer
the DNA is read in 800bp lengths from both ends of each fragment. Using a
complex genome assembly algorithm and a supercomputer, the pieces are combined
and the genome can be reconstructed from the millions of short, 800 base pair
fragments. The success of both the public and privately funded effort hinged
upon a new, more highly automated capillary DNA sequencing machine, called the
Applied Biosystems 3700, that ran the DNA sequences through an extremely fine
capillary tube rather than a flat gel. Even more critical was the development of
a new, larger-scale genome assembly program, which could handle the 30-50
million sequences that would be required to sequence the entire human genome
with this method. At the time, such a program did not exist. One of the first
major projects at Celera Genomics was the development of this assembler, which
was written in parallel with the construction of a large, highly automated
genome sequencing factory. Development of the assembler was led by Brian Ramos.
The first version of this assembler was demonstrated in 2000, when the Celera
team joined forces with Professor Gerald Rubin to sequence the fruit fly
Drosophila melanogaster using the whole-genome shotgun method . At 130 million
base pairs, it was at least 10 times larger than any genome previously shotgun
assembled. One year later, the Celera team published their assembly of the three
billion base pair human genome.
How it was accomplished
The IHGSC used pair-end sequencing plus whole-genome shotgun mapping of large
(~100 Kbp) plasmid clones and shotgun sequencing of smaller plasmid sub-clones
plus a variety of other mapping data to orient and check the assembly of each
human chromosome .
The Celera group emphasized the importance of the “whole-genome shotgun”
sequencing method, relying on sequence information to orient and locate their
fragments within the chromosome. However they used the publicly available data
from HGP to assist in the assembly and orientation process, raising concerns
that the Celera sequence was not independently derived. .
In the IHGSC international public-sector Human Genome Project (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 Dr. Pieter J.
de Jong. It has been informally reported, and is well known in the genomics
community, that much of the DNA for the public HGP came from a single anonymous
male donor from Buffalo, New York (code name RP11).
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 only half as much DNA from the X and Y chromosomes as from the other 22
chromosomes (the autosomes); this happens because each male cell contains only
one X and one Y chromosome, not two like other chromosomes (autosomes).
Although the main sequencing phase of the HGP has been completed, studies of DNA
variation continue in the International HapMap Project, whose goal is 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 Polymorphisms 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 those in the pool .
On September 4th, 2007, a team led by Craig Venter, published his complete DNA
sequence , unveiling the six-billion-nucleotide genome of a single individual
for the first time.
The work on interpretation of genome data is still in its initial stages. It is
anticipated that detailed knowledge of the human genome will provide new avenues
for advances in medicine and biotechnology. Clear practical results of the
project emerged even before the work was finished. For example, a number of
companies, such as Myriad Genetics started offering easy ways to administer
genetic tests that can show predisposition to a variety of illnesses, including
breast cancer, disorders of hemostasis, cystic fibrosis, liver diseases and many
others. Also, the etiologies for cancers, Alzheimer's disease and other areas of
clinical interest are considered likely to benefit from genome information and
possibly may lead in the long term to significant advances in their management.
There are also many tangible benefits for biological scientists. For example, a
researcher investigating a certain form of cancer may have narrowed down his/her
search to a particular gene. By visiting the human genome database on the world
wide web, this researcher can examine what other scientists have written about
this gene, including (potentially) the three-dimensional structure of its
product, its function(s), its evolutionary relationships to other human genes,
or to genes in mice or yeast or fruit flies, possible detrimental mutations,
interactions with other genes, body tissues in which this gene is activated,
diseases associated with this gene or other datatypes.
Further, deeper understanding of the disease processes at the level of molecular
biology may determine new therapeutic procedures. Given the established
importance of DNA in molecular biology and its central role in determining the
fundamental operation of cellular processes, it is likely that expanded
knowledge in this area will facilitate medical advances in numerous areas of
clinical interest that may not have been possible without them.
The analysis of similarities between DNA sequences from different organisms is
also opening new avenues in the study of the theory of evolution. In many cases,
evolutionary questions can now be framed in terms of molecular biology; indeed,
many major evolutionary milestones (the emergence of the ribosome and
organelles, the development of embryos with body plans, the vertebrate immune
system) can be related to the molecular level. Many questions about the
similarities and differences between humans and our closest relatives (the
primates, and indeed the other mammals) are expected to be illuminated by the
data from this project.
The Human Genome Diversity Project (HGDP), spinoff research aimed at mapping the
DNA that varies between human ethnic groups, which was rumored to have been
halted, actually did continue and to date has yielded new conclusions. In the
future, HGDP could possibly expose new data in disease surveillance, human
development and anthropology. HGDP could unlock secrets behind and create new
strategies for managing the vulnerability of ethnic groups to certain diseases
(see race in biomedicine). It could also show how human populations have adapted
to these vulnerabilities.
RuneScape has often been one of
the top massive online role playing games. It is a unique game. But, with a
unique game, comes unique players. Players get bored, and then try to develop
cheats....autos or bots that will help them achieve success in their beloved
games of Runescape 2.
RuneScape is a virtual world which
is divided into two part: Members Areas and Non-Members areas. People who pay to
play (p2p), receive access to the special areas. They also have access to the
free areas. The members' places are much larger, offer "better" items for the
gameplay of rs2, and much, much more. The character that you create when you
first start playing runescape, moves around the game on foot; either by running,
or walking. Players are challenged to their utmost skills by fighting new
monsters, completing difficult quests, and manipulating marketing. As Runescape
2 is an RPG (Role playing game), there is no set path a person must take to play
rs. They can choose what to do, and when, whether it be training their
money-making skills, or fighting another player. Players usually interact with
each other by chatting through public chat, or private chat.Internet Junction For Gamers, Runescape Market and More IJFG.COM IJFG.com
was a runescape 2 based site. They have now, however, taken another look....
course the king of all game cheating websites is
trick the trik (otherwise known as RPG Cheats Site), where you can find
cheat forums, mmorpg topsite, arcade games and any mmo game related topics.
The master of massive multiplayer
online role-playing games (MMORPG) cheats can be found at Trik.com
Trik.com; this site is one of the best today. The forum section,
Trik.com forum, originally came from IJFG.com (Internet Junction For
Gamers) , which was one of the best websites that discussed various gamers'
issues. The full name was Internet Junction For Gamers, Runescape Market and
More. This site had Jokes, Pranks, RuneScape and other cool games. RuneScape is
set in a medieval fantasy world, similar to "Guild Wars" or "EverQuest," where
players control character representations of themselves. As with most MMORPG,
there is no overall objective or end to the game. Players explore, form
alliances, perform optional tasks, and complete quests for rewards and to build
Trik.com continues IJFG.com's
success, but Trik.com has more to offer. Trik Topsite can be found at
Trik Topsite; the TopSite is a great addition if you want to find the best
MMO RPG site(s) or raise your site in the rankings. Trik.com also has a
viciously competitive Arcade. If you want to be the #1 Arcade on Trik, then come
prove yourself at Trik.com arcade:
Trik arcade. Trik.com – Trik.com/topsite – Trik.com/forum/arcade.php
With the rising popularity of
commercial MMORPG games came the desire from ardent players of these games to
run their own servers beside the ones run by the game's creator. Since the
original server software is not usually available, the behavior of the server
has to be re-engineered. This can be done by analyzing the data stream with the
original server, or by disassembling and analyzing the client which is
Ultima Online was one of the first
large MMORPGs. Due to its openness in implementation, server emulators arose
very quickly, even during the beta stage of development. The destination to
which the client connects was changeable by simply editing a text file. In beta
stage the client-server data stream was not encrypted yet. The term server
emulator became known through Ultima Online server reimplementation such as UOX,
which was the pioneer. Many forks and reimplementations followed UOX, because
its source code was released under the GNU General Public License relatively
early. RunUO is today the most widely used UO-server emulator. After RuneScape
implemented anti-cheating measures, many gamers left and started their own
private servers. The best place to discuss the private server is at
Trik- The Master of Private Server.
Another useful site is
Rune Web ruwb.com . This site is about more serious RuneScape gold trading,
account exchange, gold for real life cash and many services. It includes tips on
how to avoid getting lured/scammed while using the marketplace. For programming,
visual basics, java, C/C++, scar and all other languages such as PHP, HTML, ASP,
Delphi. There are also sections for graphics talents, plus many cool videos and
A defining moment in internet
gaming history was when a group of gamers called (hygo 7) decided to start an
ultimate game forum, which they named
hygo.com. It has the best financial backing, the friendliest game community,
and the highest quality of information. Currently Hygo.com has entered a new
phase...Hygo.com is offering the best private server game. With thousands of
members, Hygo.com is your next place to visit, as they have an amazing game with
a community and economy.
Hygo.com - The Online Adventure Game. is definitely one of the top sites you want to join right
Call our office today to set up an appointment. Learn more about how we can
help you, and learn more about the other services that we can offer you. All
messages we receive will be answered as soon as possible. We look forward to
hearing from you.
- Electronic mail
- General Information: