Human Genome Project

Human Genome Project

The structure of DNA was found by Watson and Crick in 1953, and only in 1956 was it first known that humans had 23 pairs of chromosomes. The subsequent interval of time has bee very active in the file of Genetics.

In 1977, Fred Sanger invented the first DNA sequencing process. He opened up the possibility of working-out the entire sequence of the bases in the human DNA, a total of some three thousand million (three billion or 3 x 109).

This has been likened to a row of 15, four-drawer filing cabinets, with each drawer full of A4 paper, printed on both sides with the letters:



In 1986, the HGP was officially started in earnest, with the USE and UK full partners. In 1988, James Watson was appointed as Head of the US contingent. Following this early work, the time scale was thought to be over 20 years to crack the code, but in 1992 Europe and Japan joined forces.

The first human gene map was produced in 1996, showing the location of the 30,000 genes. (It was originally thought that there were 100,000 genes.)

New techniques and faster, more powerful computer systems allowed the first chromosome (number 22) to be fully sequenced, followed in 2000 by chromosome 21.

A high-accuracy reference sequence will be completed in 2003. The work has involved thousands of scientists in a unique worldwide collaboration.

The work has also produced a moral, social and ethical dilemma, which has resulted in the resignation of James Watson, because of patent applications being filed on DNA fragments from human genes.

The future offers great hope for improved medicine and health care, but also considerable concern for the future use of this information.

To sequence a gene, the first difficult part is to obtain the gene. Once obtained, there are laborious manual methods, or those using machines do the process.

The manual methods involves electrophoresis; a process that separates fragments of DNA by using an electrical current.

  1. Using 4 exact samples of a fragment of DNA, a separate sequencing reaction is carried out for each of the 4 bases - T,G,C and A.
  2. In addition to the normal DNA, modified nucleotides are also added - one to each of the four samples. These stop synthesis of DNA when they are reached.
  3. DNA is initiated from a primer (which is labelled with a radioactive isotope).
  4. A series of different sized fragments of DNA are produced from the primer starting point, and these are loaded into the electrophoresis tank, for separation.

Finding the gene is relatively easy, but only if the gene in question is active in a cell.

For example: the gene for α and β haemoglobin would be expected in red blood cells. The mRNA for these proteins will be in the cytoplasm. When isolated, this mRNA can be used to generate cDNA with the help of reverse transcriptase and a collection of building blocks of nucleotides.

One of the main project goals is to address the ethical, legal and social issues (ELSI) that may arise from the project. 3-5% of the HGP budget has been set-aside for this purpose.

Knowledge about the effects of DNA variations amongst individuals can lead to diagnosis and possibly treatment of the thousands of disorders that afflict humans all over the world.

Learning about the DNA of other organisms can lead to a better understanding of their natural capabilities in solving challenges in health care, energy sources, agriculture and environmental conservation.

Questions still to answer:

  • The testing for genetic predisposition has many implications.

    Would it be acceptable to have this information known, for example, when applying for health insurance?

  • Who should decide on these tests and on whom they should be used?
  • Who should decide on these tests and on whom they should be used?
  • Through the developing genetic technologies many medical; treatments made possible will initially be very expensive, and their restricted availability will add considerably to the problems faced by healthcare trusts in deciding who is eligible for such treatments.
  • Pharmacogenomics may allow doctors to optimise the doses and suitability of drugs, which normally fail or have harmful side affects in certain individuals. These differences will be known if their genotype is available.

    Should this allow certain drugs to be given licences that at present are refused?

  • In 1991, shortly after the HGP got underway, the Director of the National Institute of Health (NIH) in America filed applications for patents on 6122 fragments of DNA. As a result, James Watson resigned as the NIH genome project leader.

    The President of the USA and the UK Prime Minister have issued a statement in March 2000, declaring that all genetic data should be released into the public domain and not restricted by patent.

The discovery of the final chapter in the 'Book of Life' has been described as, not the end, but the start of the biggest revolution in Biological Sciences.