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The Human Genome Project (HGP) was the international, collaborative research
program whose goal was the complete mapping and understanding of all the genes of
human beings. All our genes together are known as our "genome". In February 2001,
the Human Genome Project (HGP) published its results to that date: a 90 percent
complete sequence of all three billion base pairs in the human genome (National
Human Genome Research Institute, 2012).
According to Chial (2008), Approximately 200 labs in the United States were funded
by either the National Institutes of Health or the U.S. Department of Energy to support
these efforts.
Trust Sanger Institute (2013) explained that to sequence the human genome as
accurately as possible, researchers developed the 'hierarchical shotgun' method. In
this approach, genomic DNA is cut into pieces of about 150 Mb and inserted into BAC
vectors, transformed into E. coli where they are replicated and stored. The BAC
inserts are isolated and mapped to determine the order of each cloned 150 Mb
fragment. This is referred to as the Golden Tiling Path. Each BAC fragment in the
Golden Path is fragmented randomly into smaller pieces and each piece is cloned into
a plasmid and sequenced on both strands. These sequences are aligned so that
identical sequences are overlapping. These contiguous pieces are then assembled
into finished sequence once each strand has been sequenced about 4 times to
produce 8X coverage of high quality data (Department of Biology, Davidson College,
Davidson, 2002).
The other technique, known as whole genome shotgun sequencing, brings speed
into the picture, enabling researchers to do the job in months to a year (Triverdi,
2000). This approach was developed and perfected on prokaryotic genomes which
are smaller in size and contain less repetitive DNA. Shotgun sequencing randomly
shears genomic DNA into small pieces which are cloned into plasmids and sequenced


on both strands, thus eliminating the BAC step from the HGP's approach. Once the
sequences are obtained, they are aligned and assembled into finished sequence
(Department of Biology, Davidson College, Davidson, 2002). The shotgun method was
developed by GNN president J. Craig Venter in 1996 when he was at the Institute for
Genomic Research (TIGR) Venter left the NIH and became founder and chairman of
the board of the said institution (Triverdi, 2000).
Summing it up, in whole genome shotgun sequencing, the entire genome is sheared
randomly into small fragments (appropriately sized for sequencing) and then
reassembled. In hierarchical shotgun sequencing, the genome is first broken into larger
segments. After the order of these segments is deduced, they are further sheared into
fragments appropriately sized for sequencing (Trust Sanger Institute, 2013).
Chial, H. (2008). DNA Sequencing Technologies Key to the Human Genome Project.
Retrieved October 21, 2014, from http://www.nature.com
Department of Biology, Davidson College, Davidson (2002). Sequencing Whole
Genomes Hierarchical Shotgun Sequencing v. Shotgun Sequencing. Retrieved




National Human Genome Research Institute (2012). An Overview of the Human
Genome Project What was the Human Genome Project?. Retrieved October 21,
2014, from http://www.genome.gov/12011238
Trivedi, B. (2000, June 2). SEQUENCING THE GENOME. Retrieved October 21,

from http://www.genomenewsnetwork.org

Trust Sanger Institute (2013). The Human Genome Project: A new reality. Retrieved
October 21, 2014, from https://www.sanger.ac.uk/about/history/hgp/