HUMAN GENOME PROJECT

The Human Genome Project aimed to map the entire genome, including
the position of every human gene along the DNA strand, and then to
determine the sequence of each gene’s base pairs. At the time, 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
of the human genome, and had begun the task of working out the functions
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
was making it clear that an organism's complexity is not necessarily related
to its number of genes.

Human genes categorized by function of the transcribed proteins, given both as number of encoding genes and
percentage of all genes

Also, while we might have a surprisingly small number of genes, they are
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
fishTetraodon nigroviridis has more genes than we do—nearly 28,000—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, the complete final map of the Human Genome was announced. The
DNA from a large number of donors, women and men from different nations
and of different races, contributed to this ‘typical’ Human Genome
Sequence.

The process of identifying

the boundaries between
genes and other features
in a raw DNA sequence is
called genome
annotation and is in 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.
Beginning in 2008, a new
technology known as RNA- The first printout of the human genome to be presented as a
seq was series of books, displayed at the Wellcome Collection,
London

Introduced that allowed scientists to directly sequence the messenger RNA

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
every human tissue using RNA-seq. These experiments have revealed that
over 90% of genes contain at least one and usually several alternative
S splice variants, in which the exons are combined in different ways
to produce 2 or more gene products from the same locus.
The genome published by the HGP does not represent the sequence of
every individual's genome. It is the combined mosaic of a small number of
anonymous donors, all of European origin. The HGP genome is a scaffold
for future work in identifying differences among individuals. Subsequent
projects sequenced the genomes of multiple distinct ethnic groups, though
as of today there is still only one "reference genome.

FINDINGS
Key findings of the draft (2001) and complete (2004) genome sequences
include:

1. There are approximately 22,300 protein-coding genes in human

beings, the same range as in other mammals.
2. The human genome has significantly more segmental duplications
(nearly identical, repeated sections of DNA) than had been previously
suspected. At the time when the draft sequence was 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
developing treatments. It is considered a Mega Project because the human
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.
It was far too expensive at that time to think of sequencing patients’ 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,
since the major diseases are common, so too would be the genetic variants
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. (In 2002 the National Institutes of Health started a $138 million
dollar project called the Hap Map to catalog the common variants in
European, East Asian and African genomes.)

The genome was broken into smaller pieces; approximately 150,000 base
pairs in length. These pieces were then ligated 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.
Funding came from the US government through the National Institutes of
Health in the United States, and a UK charity organization, the Wellcome
Trust, as well as numerous other groups from around the world