BIOLOGYPROJECT

HUMANGENOME
PROJECT

DONE BY:
BHAVISHRADHAN
 4

CONTENTS
[Link] TOPIC PAGE NO.
1. Introduction 5
2. Why study our 8
genome
3. Human 10
Genome Project
4. Ethical Legal 14
Social Issues
5. Observation 15
6. Conclusion 16
7. Bibliography 17
 5

INTRODUCTION
Although every person on our planet is built from the same
blueprint, no two people are exactly the same. While we are
similar enough to readily distinguish ourselves from other living
[Link] it
that makes us all human, yet unique? Our DNA.

THESTUFFTHATMAKESUSWHOWEARE
Our DNA (DeoxyriboNucleic Acid) is found in the nucleus of
everycellinourbody(apartfromredbloodcells,whichdon’t have a
nucleus). DNA is a long molecule, made up of lots of smaller
units. To make a DNA molecule you need:

 nitrogenousbases—therearefourofthese:adenine(A),
thymine (T), cytosine (C), guanine (C)
carbonsugarmolecules
phosphate molecules
If you take one of the four nitrogenous bases, and put it together 6

with a sugar molecule and a phosphate molecule, you get a

[Link]
nucleotide bases together to form a single strand of DNA.
Two of these strands then wind around each other, making the
twisted ladder shape of the DNA double helix. The nucleotide
bases pair up to make rungs of the ladder, and the sugar and
[Link] in
specific combinations: A always pairs with T, and C always pairs
with G to make base pairs.

Put three billion of these base pairs together in the right order,
and you have a complete set of human DNA—the human
[Link].

It’s the order in which the base pairs are arranged—their

sequence—inourDNAthatprovidestheblueprintforallliving
[Link] base 7

pairs in a fish’s DNA is different to those in a monkey.

The base pair sequence of all people is nearly identical—that’s

what makes us all humans. However, there are small differences
in the order of the three billion base pairs in everyone’s DNA that
causethevariationsweseeinhaircolour,eyecolour,noseshape etc.
No two people have exactlythe same DNA sequence (except for
identical twins, because they came from a single egg that split
into two, forming two copies of the same DNA).

IdenticalTwins

Populationwithwiderangeof characters

We get our DNA from our parents. The DNA of the human
genome is broken up into 23 pairs of chromosomes (46 in total).
We receive 23 from our mother and 23 from our father. Egg and
sperm cells have only one copy of each chromosome so that
whentheycometogethertoformababy,thebabyhasthenormal 2
copies. Three billion is a lot of base pairs, and together they
contain an enormous amount of information.
 8

WHYSTUDYOURGENOME?
Working out the sequence of the base pairs in all our genes
enables us to understand the code that makes us who we are.
This knowledge can then give us clues on how we develop as
embryos, why humans have more brainpower than other animals
and plants, and what happens in the body to cause cancer. But
establishingthesequenceofthreebillionbasepairsisaBIGtask. The
great and ambitious research program that sought to do this was
called the Human Genome Project.

FrancisCollins,formerdirectoroftheNationalHuman
Genome Research Institute, led theHuman
Genome Project.

The idea of the Human Genome Project was born in the 1970s,
when scientists learned how to ‘clone’ small bits of DNA, around
[Link], scientistscutoutafragment of
human DNA from the long strand and then incorporate it into the
genomeofabacteria,[Link]
replicated within the bacterial cell many times and every time the
bacterial cell divides, the new cells also contain the introduced
D
DNA fragment. Bacterial cells reproduce prolifically, and so this 9
process ends up making millions of cells that all contain the
introducedDNAfragment,enoughthatresearcherscanstudyitin detail
and figure out the sequence of the base pairs.

With time, researchers have been able to study an ever greater

number of different DNA fragments, that is, different genes. It
became clear that certain variant DNA sequences were
associated with particular conditions: diseases such as cystic
fibrosisorbreastcancer,ornormal,non-harmfulvariantslikered
[Link]
Project, even from some scientists. Considering only around 1.5
per cent of our genome is actual genes that code for proteins, it
was thought that much of the $3 billion cost to sequence the
entire human genome would be wasted on the ‘junk’ DNA that
scientists thought didn’t get used. The important role the ‘junk’
DNAplaysingeneregulationwasn’tyetappreciated.

Research groups in many

countries, including
Australia, began to
sequence different genes,
providing the beginnings of
[Link]
1989, the Human Genome
Organization (HUGO) was
A cell in human body is simply invisible to naked
eye, Microscopes are essential to view them. A found by leading scientists
HumanDNAwhichisabout2mlonggetspackedso well
that it fits into cell nucleus, then think of the difficulty
to coordinate the massive
in viewing a DNA

Internationaleffortinvolvedincollectingsequencedatatounravel the
secrets of our genes.
 HUMANGENOMEPROJECT 10

TheHumanGenomeProjectaimedtomaptheentiregenome,including the
position of every human gene along the DNA strand, and then to
determinethesequenceofeachgene’[Link],sequencing even
a small gene could take months, so this was seen as a stupendous and
very costly undertaking. Fortunately, biotechnology was advancing rapidly,
and by the time the project was finishing it was possible to sequence the
DNA of a gene in a few hours. Even so, the project took ten years to
complete; the first draft of the human genome was announced in June
2000.

In February 2001, the publicly funded Human Genome Project and the
private company Celera both announced that they had mapped virtually all
ofthehumangenome, andhadbegunthetaskofworkingoutthefunctions of the
many new genes that were identified. Scientists were surprised to find that
humans only have around 25,000 genes, not much more than the
roundworm Caenorhabditis elegans, and less than a tiny water crustacean
called Daphnia, which has around 30,000. However, genome sequencing
wasmakingitclearthatanorganism'scomplexityisnotnecessarilyrelated to its
number of genes.

Humangenescategorizedbyfunctionofthetranscribedproteins,givenbothasnumber of
encoding genes and percentage of all genes.
Also, while we might have a surprisingly small number of genes, they are 11
often expressed in multiple and complex ways. Numerous genes have as
many as a dozen different functions and may be translated into several
different versions active in different tissues. We also have a lot of extra
DNA that doesn’t make up specific genes. So even though the puffer
fishTetraodonnigroviridishasmoregenesthanwedo—nearly28,000—the size
of its entire genome is actually only around one tenth of ours as it has
much less of the non-coding DNA.

In April 2003, the 50th anniversary of the publication of the structure of

DNA,[Link] DNA
from a large number of donors, women and men from different
nationsandofdifferentraces,contributedtothis‘typical’HumanGenome
Sequence.

Theprocessofidentifying
the boundaries between
genes and other features
inarawDNAsequenceis
called genome
annotation and is in the
domain of bioinformatics.
While expert biologists
make the best annotators,
theirworkproceedsslowly,
and computer programs
are increasingly used to
meet the high-throughput
demands of genome
sequencing projects.
Beginning in 2008, a new
technologyknownasRNA- Thefirstprintoutofthehumangenometobepresentedasaseries
seq was of books, displayed at the Wellcome Collection,London

Introducedthat allowed scientiststodirectlysequencethemessengerRNA in

cells. This replaced previous methods of annotation, which relied on
inherent properties of the DNA sequence, with direct measurement, which
was much more accurate. Today, annotation of the human genome and
other genomes relies primarily on deep sequencing of the transcripts in
[Link] over
90% of genes contain at least one and usually several alternative
S
splicevariants,inwhichtheexonsarecombinedindifferentwaysto produce 2 or
12
more gene products from the same locus.

The genome published by the HGP does not represent the sequence of
everyindividual's genome. It is thecombined mosaic of a small number of
anonymous donors, allof Europeanorigin. TheHGPgenome is ascaffold for
future work in identifying differences among individuals. Subsequent
projectssequencedthegenomesofmultipledistinctethnicgroups,though as of
today there is still only one "reference genome.

FINDINGS
Keyfindingsofthedraft(2001)andcomplete(2004)genomesequences include:

1. Thereareapproximately22,300protein-codinggenesinhuman
beings, the same range as in other mammals.
2. The human genome has significantly more
segmentalduplications(nearlyidentical,repeatedsectionsofDNA)th
anhad
[Link]
published fewer than 7% of protein families appeared to be
vertebrate specific.

ACCOMPLISHMENT
The Human Genome Project was started in 1990 with the goal of
sequencing and identifying all three billion chemical units in the human
genetic instruction set, finding the genetic roots of disease and then
[Link] MegaProjectbecausethehuman
genome has approximately 3.3 billion base-pairs. With the sequence in
hand, the next step was to identify the genetic variants that increase the
risk for common diseases like cancer and diabetes.
Itwasfartooexpensiveatthattimetothinkofsequencingpatients’whole genomes.
So the National Institutes of Health embraced the idea for a "shortcut", which
was to look just at sites on the genome where many

people have a variant DNA unit. The theory behind the shortcut was that,
sincethemajordiseasesarecommon,sotoowouldbethegeneticvariants that
caused them. Natural selection keeps the human genome free of variants
that damage health before children are grown, the theory held, but fails
against variants that strike later in life, allowing them to become quite
 Common.(In2002theNationalInstitutesof Health starteda $138million dollar 13
project called the Hap Map to catalog the common variants in European,
East Asian and African genomes.)
The genome was broken
into smaller pieces;
approximately150,000base
pairs in length. These
pieces were then ligatedinto
a type of vector known as
"bacterial
artificialchromosomes", or
BACs, which are derived
from bacterial
chromosomes
whichhavebeengenetically
engineered. The vectors
containingthegenescanbe
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
[Link],
150,000 base pairs go
together to create
chromosomes. This is
known as the
"hierarchicalshotgun"
approach, because the
genome is first broken into
A,ForeachTetraodonchromosome,colouredsegmentsrepresent relatively large chunks,
conserved synteny with a particular humanchromosome. which are then mapped to
Synteny is defined as groups of two or
moreTetraodongenesthatpossessanorthologueonthesamehum
chromosomes before being
anchromosome,irrespectiveof orientation or selected for sequencing.
order. Tetraodon chromosomes are not in descending order Funding came from the US
bysize because of unequal sequence coverage. The entire government through the
mapincludes 5,518 orthologues in 900 syntenic segments. B, National Institutes of Health
Onthe human genome the map is composed of 905
in the United States, and a
[Link]
syntenymapbetween Tetraodon and mouse UK charity organization,
theWellcomeTrust,aswell as
numerous other groups from
around the world.
 14
ETHICAL,LEGAL&SOCIAL
ISSUES
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
InsurancePortability and Accountability Act (HIPAA) which protects against
the unauthorized and non-consensual release of individuallyidentifiable
health informationtoanyentitynot
activelyengagedintheprovisionofhealthcare services to a patient.
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
percentoftheannualbudgetwasallocated to
address the ELSI arising from the project.
This budget started at approximately $1.57
million in the year 1990, but increased to
approximately $18 million in the year 2014.
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.
"Molecularisingdiseaseandtheirpossiblecurewillhaveaprofoundimpact on
what patients expect from medical help and the new generation of doctors'
perception of illness."
OBSERVATION 15

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
more than 95% of the genome. The other regions, called
"heterochromatic" are found in centromeres and telomeres, and were not
sequenced under the project.
[Link] 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
genomesequencewaspublishedonMay27,2004indicatingover92%of
sampling exceeded 99.99% accuracy which was within the intended
[Link] occur.

AresearcherreviewsaDNAsequence.
 16
CONCLUSION
There is no doubt that information from the Human Genome Project
provideshugebenefitstohumanhealthinhelpingtounderstandandtreat genetic
diseases (such as breast cancer, cystic fibrosis and sickle cell anaemia).
However, some people see ethical issues, and wonder if
scientistsare“playingGod”withourgenomes.

Could genetic information be misused; for example, through genetic

discrimination by employers or insurance companies? Most people agree
thatgenetestingcanbeusedethicallytopreventseriousdiseasessuchas cancer,
or during pregnancy to avoid the birth of someone with a severe handicap,
but should we allow gene testing to choose a child who will be able to be
better at sports, or more intelligent? What about sex selection, already a
problem in some countries? And will it become possible to use genetic
informationtochangegenesinchildrenoradultsfor the better?Do we really
want to know if we run the risk of developing a particular disease that may
or may not be treatable? What are the privacy issues regarding genome
screening on a population scale? Still many more such questions arise and
leave us in oblivion of deep thoughts, yet we need to believe in science and
its advancements and realize that with NEW KNOWLEDGE COMES
HUGE NEW RESPONSIBILITIES.
 17

BIBLIOGRAPHY
 Biology Textbook Class - XII
 [Link]
 [Link]
 [Link]
 [Link]