Human Genome Project (HGP)

Genome refers to the total DNA in a haploid set of chromosomes of a cell of an individual.
Understanding the genome depends on the sequencing of nucleotides in the DNA. The ultimate goal of DNA sequencing is the human genome.

Human genome project was an international scientific research project with the goal of determining base pairs that make up the human DNA, and of identifying and mapping all the genes of human genome from both physical and functional standpoint. The project was facilitated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and worldwide partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Organization (HUGO), an international organization of scientists involved in genetics, was responsible for gathering and distributing information on human genomerelated projects. They also offered their expert advice to agencies, both governmental and nongovernmental, on supporting human genome research. This project was launched formally in 1990 and was declared complete on April 14, 2003.

Figure 01: The Human Genome Organization (HUGO) is an international collaboration of scientists involved in genetics. Source: www.hugo-international.org

Objectives of human genome project

1. To identify all the approximate 20,000-25,000 genes in human DNA and to assign them to their respective chromosomes.
2. To determine sequence of all (2.3*10 raised to the power 9) base pairs.
3. To store this information in database.
4. To improve tools for data analysis.
5. To address the ethical, legal and social issues (ELSI) that may arise from the project.
6. To transfer related technologies to the private sector.

The major ELSI goals for the next 5 years

1. Examine the issues surrounding the completion of the human DNA sequence and the study of human genetic variation.
2. Examine issues raised by the integration of genetic technologies and information into health care and public health activities.
   
3. Examine issues raised by the integration of knowledge about genomics and gene-environment interactions into nonclinical settings.
4. Explore ways in which new genetic knowledge may interact with a variety of philosophical, theological, and ethical perspectives.
5. Explore how socioeconomic factors and concepts of race and ethnicity influence the use, understanding, and interpretation of genetic information, the utilization of genetic services, and the development of policy.

Methodology

1. Identifying all the genes which are expressed as RNAs are called Expressed Sequence Tags (ESTs).
2. Initially sequencing the whole genome irrespective coded and non-coded regions.
3. Then assorting the coded posts using sequence annotation (SA).

Steps

1. The whole genome is fragmented using particular restriction endonuclease enzyme.
2. Then the cloned copies of DNA are sequenced as annotated DNA. It is done by using annotated DNA sequencing techniques by Fredrick Sanger.
3. The annotated fragments are then arranged into appropriate sequences with the help of overlapping regions on them.
4. Finally, the sequences are allowed to their respective chromosomes using information on polymorphism of restriction sites and microsatellites.

Figure 02: Single nucleotide polymorphisms. A SNP in three different people, where each person has a different base at the same spot in the genome. Source: http://sitn.hms.harvard.edu/flash/2019/lessons-from-the-human-genome-project/

Figure 03: Shotgun whole genome sequencing. This image shows an overview of the shotgun sequencing procedure, where DNA is copied, broken, sequenced, and computationally analyzed to figure out the original genetic sequence. Source: http://sitn.hms.harvard.edu/flash/2019/lessons-from-the-human-genome-project/

Interesting facts from the Human Genome Project(These facts reflect opinion in 2003)

1. There are between 30,000 and 40,000 genes in the human genome.
2. A human being can be made from a gene count only twice as great as that of a fly or worm.
3. We are not fruit flies or worms because some our genes work differently – we have more “control genes.”
4. Hundreds of genes appear to have come from bacteria – one of which has been associated with depression.
5. Most mutations occur in males.
6. More than one million SNPs have been identified. (Figure 02)
7. The purpose of the 97% of “junk” DNA is being discovered.
8. Just 483 existing “targets” in the body account for all the pharmaceutical drugs on the market.
9. Understanding of how the body works is dramatically increasing due to HGP knowledge. 10. Understanding of how we evolved as human beings is being rapidly advanced through “genetic archaeology.”

Outcomes

The HGP has helped us understand diseases including genotyping of specific viruses, identification of mutations linked to different forms of cancer, advancements in forensic applied sciences, biofuels, risk assessment, bioarcheology, anthropology and evolution. Another proposed benefit is the commercial develop of genomics research related to the DNA based products, a multi-billion-dollar industry.

Was the Project Successful?

It was a successful project as scientists were able to figure out all the three billion chemical bases of human genome, which were published in 2003. It has led scientists to discovery of about 1800 disease-causing genes in humans, which can help in prediction and prevention of these diseases at earlier stages. Moreover, it has been very helpful in making personalized and more efficient medicines that could be made according to the genetic information received from the patients’ genomic sequences. We have also benefitted from it in improving forensic science to accurately figure out the suspects of the crimes.

Advantages

1. Will assist in the diagnosis of disease and gene therapy, can also help in the individual plan for the same disease.
2. Will help farmers with livestock breeding, and assist us in creating disease resistant crops and animals.
3. Will assist in environmental cleanup.
4. It could improve criminal justice proceedings.

Disadvantages

1. Information obtained from HGP may bring about personal unhappiness to those who receive generic information for which they may not be prepared.
2. It can increase discrimination, affect employment and insurance coverage decisions.
3. It may result in ethical problems as to who should be given the custody of genetic information and where and how such information could be put to use.

Impact of Human Genome Project

Having the essentially complete sequence of the human genome is similar to having all the pages of a manual needed to make the human body. The challenge to researchers and scientists now is to determine how to read the contents of all these pages and then understand how the parts work together and to discover the genetic basis for health and the pathology of human disease. In this respect, genome-based research will eventually enable medical science to develop highly effective diagnostic tools, to better understand the health needs of people based on their individual genetic make-ups, and to design new and highly effective treatments for disease. Individualized analysis based on each person’s genome will lead to a very powerful form of preventive medicine. We’ll be able to learn about risks of future illness based on DNA analysis. But there will be a personalized aspect to what we do to keep ourselves healthy. Then, through our understanding at the molecular level of how things like diabetes or heart disease or schizophrenia come about, we should see a whole new generation of interventions, many of which will be drugs that are much more effective and precise than those available today.

Author: Nishinki Thakshana de Silva
B.Sc. (Special degree in BioChemistry and Molecular Biology)
Undergraduate
Faculty of Science
University of Colombo

References :
Hood, L., Rowen, L. The Human Genome Project: big science transforms biology and medicine. Genome Med 5, 79 (2013). https://doi.org/10.1186/gm483
Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004). https://doi.org/10.1038/nature03001
Emmert-Streib F, Dehmer M and Yli-Harja O (2017) Lessons from the Human Genome Project: Modesty, Honesty, and Realism. Front. Genet. 8:184. https://doi.org/10.3389/fgene.2017.00184
Olson MV. The human genome project. Proceedings of the National Academy of Sciences of the United States of America. 1993 May;90(10):4338-4344. DOI: 10.1073/pnas.90.10.4338.
https://www.sanger.ac.uk/news_item/ten-facts-human-genome-project/ (Accessed on 16.06.2020)
http://sitn.hms.harvard.edu/flash/2019/lessons-from-the-human-genome-project/ (Accessed on 16.06.2020)