Question

Essay The Human Genome Project   (No more than 3 pages, 1.15 spacing, Calibri or other standard font)

write an essay summarizing the Human Genome Project (HGP). Using a narrative format, include in your essay:

the goal and scope of the HGP

the research groups and countries that worked on the Project

the time period of the project and critical dates

the key research techniques and technologies that played major roles in the project

the key findings about the human genome

At least two major reasons why studying the genomes of other species is important to biology?

Two-three accomplishments and two challenges resulting from the completion of HGP, as expressed by some of the leading scientists, 10-15 years later.

Your thoughts about learning about the HGP and its promises and challenges.

Answer 1

• The Human Genome Project (HGP) was an international collaborative program whose goal was to complete mapping of all genes in the human genome. This concerted public effort aimed at sequencing all the 3 billion bases of the human DNA. The secondary goal was to provide enough information to the researchers regarding the molecular and genetic mechanisms underlying human diseases, such that novel strategies for diagnosis, treatment and prevention can be invented. The objectives towards the primarey goal are listed below:

1. Sequencing the human genome in entirety and store this information in accessible databases
2. Identifying the unknown human genes
3. Mapping variations across the human genomes
4. Sequencing of the genomes of mouse and four other model organisms.
5. Develop tools for data analysis and adress the ethical, social and legal issues.

• The support and funding from DOE and NIH and later from the Medical Research Council and Wellcome Trust in UK enabled the project to run over 13 years on a huge scale, ending up with a cost of 3 billion dollars. In total, the Human Genome Project team or the ‘International Human Genome Sequencing Consortium’ involved scientists from 20 institutions across six countries: France, Germany, Japan, China, the UK and the USA. But the main institutions which sequenced majority of the genome, also nicknamed as G5, were:
• Broad Institute/Whitehead Institute for Biomedical Research (MIT), Cambridge, USA
• Baylor College of Medicine, Houston, USA
• Department of Energy’s Joint Genome Institute, Walnut Creek, USA
• Washington University, St Louis, USA
• Wellcome Trust Sanger Institute, Cambridge, UK

This project of international interest had several federal agencies from US involved. 1) National Institute of Health (NIH), 2) Centers for Disease Control and Prevention (CDC), 3) Department of Energy (DOE), 4) Food and Drug Administration (FDA), 5) NIH Office of Biotechnology Activities (OBA), 6) Health Resources and Services Administration (HRSA), 7) National Science Foundation (NSF), 8) United States Department of Agriculture (USDA).

Additionally, the European Bioinformatics Institute in Cambridge, UK, and the National Centre for Biotechnology Information at the US National Institutes of Health provided the computational and analytical support for assembly of the gene sequences across the chromosomes.

• The Human Genome Project started in 1990 and was completed successfully in April 2003. This project for a period of 13 years and costing 3 billion dollars, was completed successfully under budget and two years before schedule. The proposal for sequencing the human genome was laid down in 1985, following which the Human Genome Organisation (HUGO) was founded in 1988. In 1990, the project is launched with James Watson of the famous Watson-Crick pair as the director. In 1996, the representatives of the various sequencing centres meet at Bermuda to set down the Bermuda principles that laid down the draft of principles for rapid and free access to the human genome. In 1999, large scale DNA sequencing of the human genome begins and in that year itself, the the sequence of the first human chromosome, chromosome 22, is completed. In 2000, the University of California, Santa Cruz, launches its Human Genome Browser. The first draft of the human genome was published by the International Human Genome Sequencing Consortium in February 2001 in the jounal Nature. In 2003, the "gold standard" official human genome is completed to 99.99 % accuracy.

• Some of the important techniques used in the HGP are:

1. DNA Sequencing
2. Restriction Fragment Length Polymorphism (RFLP)
3. Yeast Artificial Chromosomes (YAC)
4. Bacterial Artificial Chromosomes (BAC)
5. Polymerase chain reaction (PCR)
6. Electrophoresis
7. Computational tools to assemble the data and analyse it.

• The HGP revealed that probably there are 20,500 genes which appeared to be significantly fewer than previous estimates, which ranged from 50,000 genes to as many as 140,000. HGP has also revealed the non-coding regions of the DNA, leading to the realisation that majority of the DNA is actually junk and does not lead to any gene products . However the significance of this remains to be elucidated. The HGP has led to the discovery of approximately 1800 disease related genes and has contributed largely in the development of the field of pharmacogenomics.

• The HGP also involved genome sequencing of model organisms. This is of significance as a comparative genomics between genomes of humans and model organisms paves the path to understand evolution from the common ancestor, how a genome accumulated variations, and gives us an idea about how we evolved. It also gives us an hint about why are we suscetible or resistant to certain diseases when a overall comparison of homologous genes in human and model organisms are done.

• Accomplishments and Challenges following the HGP.
• The HGP increased the credibility of genetic screening and DNA based tests, offering detection of several diseases at a time, allowing quick diagnosis and follow up treatment, and also aids in detection of carrier in families and the likelihood of an individual in developing the disease.
• Targeted drug and immuno therapies have found a new dimension with the onset of HGP. Understanding the genetic variation between individuals can help us understand how certain individuals are susceptible or resistant to certain diseases. Additionally, the HGP helped in gene therapy techniques, leading to proper identification and replacement of defective genes.
• The HGP also led to the initiation of several other sequencing projects involving other microbes, cancer, single nucleotide polymorphisms, which allowed researchers to work with specific areas of interest. Other offshoot areas of research like anthropological studies of populations and migration patterns, arised from the HGP
• After 10-15 years post the HGP, researchers identified challenges involved with the HGP. 1) Although the HGP 's broader objective was to improve human health, it does raise of the question of how is this vast amount of information being used and interpreted, or who has access to it. 2) If there is any improper use of genetic information, is the society adapted to combat such issues? A fair use of gentic information in cases of insurance, employment, adoption, criminal justice and military is necessary. Otherwise the privacy and confidentiality of the genetic information is at risk. 3) Commercialization of products from genetic research raises the questions of ownership , leading to patents, copyright and data accessibility.

• In my opinion, the Human genome project aimed at a better understanding of the human genome, for broader implications in healthcare, risk assessment, and for solving other environmental issues. However the privacy and confidentiality of such information cannot be bargained at any cost. Though data accessibility poses such problems, but the information should be used only in the betterment of health care, allowing quick diagnosis, improved treatment and employing better preventive measures. However, discrimination in delivering treatment on the basis of such genetic information should not be encouraged. Rather issues of environmental problems such as waste management, increasing agricultural produce and ensuring safe food and drinking water quality should be strengthened.