The Human Genome Project – discovering the human blueprintIn what has been called the Everest of modern biology, scientists from around the world have worked together to unravel and record the entire set of human genetic instructions.
Key text
Back to basics You will get more from this topic if you have mastered the basics of DNA and genes – this link will take you to an annotated list of sites with helpful background information. Key textHow the project began The idea of the Human Genome Project first began in a vague way in the 1970s when biologists started to investigate human genes at the molecular level. As biochemical analysis of DNA (deoxyribonucleic acid) became possible, it became clear that certain segments of DNA (called markers) were associated with particular conditions. Various countries started to map parts of the human genome in the 1980s but the international project really got under way when the USA became involved. In 1989, the Human Genome Organisation (HUGO) was founded by leading scientists in the field to coordinate the massive international effort involved in unravelling the secrets of our genes.
The Human Genome Project – A feat so vast that at first it seemed unachievable The project aimed to map the position of every human gene and to read and decipher every message encoded in the the twisted double helix of our DNA (Box 1: Genes – the basic facts). It was a stupendous and very costly undertaking, involving advanced biotechnology, and took many years to complete. A 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 jointly announced that they had mapped the bulk of the human genome. These maps show that there are only about 30,000 genes – many fewer than the 100,000 expected. In April 2003, the 50th anniversary of the publication of the structure of DNA, the completed map, was announced. The final sequence covers 99 per cent of the gene-containing regions of the genome. Australia plays its part Despite its strong contributions to biological and medical research, Australia has been slow to become involved in large-scale genome research. Few of our institutions have had the funding or facilities to undertake such projects. The establishment of the Australian Genome Research Facility in 1995 provided Australia with a facility for DNA sequencing and is now Australia's largest provider of genomic services (Box 2: Gene mapping and DNA sequencing).
The controversy There is no doubt that information from the Human Genome Project will provide huge benefits to human health with the diagnosis and possible treatment of genetic diseases (eg, cystic fibrosis and Huntington's chorea). However, some people feel that the huge amounts of money being spent on the project could have been used to improve the human condition in more effective ways. Genetic information can be misused; for example, through genetic discrimination by employers or insurance companies. The ethical, legal and social issues (ELSI) associated with genetic information have been considered by the US Department of Energy and National Institutes of Health under the world's largest bioethics program. The completion of the project and the issues associated with it will be an essential part of modern biology for years to come. Related Nova topics: Biology meets industry – genomics, proteomics, phenomics
Genes are made of DNA To understand genes, we must first understand DNA (deoxyribonucleic acid) – the stuff of which genes are made. DNA is an enormously long, thin molecule, composed of compounds called bases strung together like beads in a necklace. Each DNA molecule is made of two strands of DNA intertwined together. Within the DNA are four different types of bases (adenine, thymine, guanine and cytosine – often referred to by their first letters: A, T, G and C), each base is paired with another base on the opposing strand. The order in which the base pairs are arranged can be used to send a message – usually an instruction to other biological molecules about what to do and what to make. That is why bases are sometimes said to comprise the genetic alphabet. Some stretches of DNA have no obvious function Just as the letters in a whole book are not all stuck together, so DNA bases are organised into the equivalent of individual words, paragraphs or chapters. There is also punctuation and, it appears, plenty of gibberish that conveys nothing – probably the result of past errors in the copying process that takes place during reproduction. Stretches of DNA with no obvious function are sometimes referred to as junk DNA or non-coding DNA. The discovery of microRNA and its role in development has led to a new appreciation of parts of the genome that were once considered ‘junk DNA’. Genes contain information to make proteins A gene is a sequence of DNA bases that typically codes for a protein. Proteins in turn manufacture and control all the living processes. For example, the gene for brown eyes is an instruction that gets the cells in the iris of the eye to make a dark pigment. A different sequence of bases would spell a different message with different consequences – rather like spelling out a different sentence using the same letters of the alphabet. DNA molecules are organised into chromosomes Each normal cell in an individual’s body (apart from egg or sperm cells) contains identical DNA molecules, organised into manageable units called chromosomes. In humans each cell contains 22 pairs of autosomes plus two sex chromosomes. Males have an X and a Y; females have two Xs. But not every gene is necessarily switched on in every cell. For example, the cells that make pigment in the eye also contain the genes for making tooth enamel or liver tissue but, fortunately, don’t do so because those genes are inactive. The genome refers to all the genes within a species Taken together, all the genes within a living thing or within a species are called the genome. Naturally, there are slight differences in the sequence of DNA bases between individuals of a species, but it’s obvious that all humans have more characteristics in common than they do differences. The amount of information needed to make a living thing is staggering If you’ve ever tried to follow do-it-yourself instructions to assemble a piece of furniture, you’ll realise how nightmarishly complicated would be the task of putting together a living thing. Although scientists are not yet in the business of much organism-building, they are already at the stage of trying to read and puzzle out all the instructions. Very simple organisms, such as tiny viruses, can be made with only a few genes. Even though they are simple and small, each virus gene is still hundreds of thousands of DNA bases long. The first complete viral genome was worked out in 1977 in the United Kingdom by Dr Fred Sanger, a double Nobel laureate in science. Since then, molecular biologists have succeeded in reading the entire message of several viral genomes. Recently it was announced that the genome of a common yeast species has also been sequenced (ie, all the bases have been read). The information to make a yeast cell is a staggering 15 million bases. But when we move to organisms larger than a single cell, the amount of information we are faced with makes a multi-volume encyclopaedia look like a comic book. Consider this: a tiny worm has 80 million letters in its genetic library; the fruit fly has 155 million. And humans? Well, we don’t have the most by any means, but we do weigh in with a hefty 2800 million. That’s why the Human Genome Project is such a massive undertaking. Related sites
Where loci for different genes are on the same chromosome they are said to be linked because usually they will all be passed on together to the offspring. However, sometimes chromosomes can break and re-join, and the genes that are usually linked become separated. The chance of separation of linked genes depends on how close together the loci of the genes are. If they are close together crossing over between them is rare. The further apart they are the greater is the chance of crossing over happening between them. Therefore the frequency of crossing over can be used as a measure of distance between genes. From these kinds of data it is possible to produce a genetic linkage map of chromosomes. Scientists are now producing other kinds of gene maps. After cloning large amounts of DNA from the genome, they use markers to connect the cloned pieces correctly. This information is then used to produce a physical map. The object of physical mapping is to create complete sets of cloned DNA pieces that span every region of a chromosome and even the whole human genome. DNA sequence maps are also a kind of gene map. Knowing the sequence of bases – the chemical building blocks that make up the DNA strand – is important because it tells scientists what kind of genetic information the DNA carries in that particular segment. Scientists also use sequence information to sort out which stretches of DNA contain genes and to analyse genes for changes in sequence that may cause disease. Related sites
Teachers notes
Do library research to fill in the table for at least five genetic diseases. In the comments column you could refer to such things as the advantages and disadvantages of diagnosis, the possibility of treatment and the likely impact of the Human Genome Project. Teachers notes Students should be able to find information on the following diseases: Huntington disease; cystic fibrosis; thalassaemia; phenylketonuria; haemophilia; Turner syndrome and Klinefelter syndrome.
Use ideas raised by other people in your group to help you decide whether you think the Human Genome Project should have been established. Take a class vote to find out the overall opinion of the class. Teachers notes As the Human Genome Project is a controversial issue there is no right answer. Taking a class vote is only useful as an indicator of the most common opinion in the class. Encourage students who disagree with the majority opinion to realise that, provided their opinions are based on well-reasoned arguments, they are just as acceptable as the majority opinion. Arguments for could include the unforeseen benefits that come from pure research, and increasing our understanding of human genes and human health by:
In addition there are other spin-offs such as:
Arguments against could include:
Australasian Science September 2003, pages 38-40 The common thread (by Stephen Luntz) An interview with Sir John Sulston about how close society came to losing control over ownership of our genes.
August 2003, pages 20-22 The legal helix (by Matthew Rimmer) Explains the legal issues over access to sequence data that are unravelling public research.
Nature A collection of Nature articles on human genomics is available.
New Scientist A collection of articles on genetics and genes is available.
6 December 2006 Genomic atlas of the mouse brain revealed (by Peter Aldhous) Reports on a genomic atlas of the mouse brain.
22 November 2006 Human DNA is far more varied than thought (by Debora MacKenzie) Research suggests that humans may differ due to differences in the number of copies of genes.
18 November 2006 Human genome: The end of the beginning (by Andy Coghlan and Nell Boyce) Looks back on the announcement of the completion of the human genome project.
15 November 2006 Neanderthals have genome chunk sequenced (by Dan Jones) Announces the sequencing of over a million base pairs of fossilised Neanderthal DNA.
11 October 2006 Neanderthal DNA illuminates split with humans (by Roxanne Khamsi) Sequencing of Neanderthal DNA suggests that humans and Neanderthals are distant relatives.
19 August 2006, ages 29-36 All about me (by Dan Jones) Discusses the role of genes in the development of the mind, personality and behaviour.
15 April 2006, page 32 Genome-in-a-day promised as DNA is put through hoops (by Andy Coghlan) Describes future rapid DNA sequence analysis using magnetic codes.
8 April 2006, pages 38-41 Magic numbers (by Bob Holmes) Looks at the role of chromosome deletions or duplications – gene copy number – in diseases.
7 March 2006 Many human genes evolved recently (by Melissa Lee Phillips) Suggests that human genes involved in metabolism, skin pigmentation, brain function and reproduction evolved in response to recent environmental changes.
21 January 2006, pages 8-9 One million people, one medical gamble (by Andy Coghlan) Describes the ‘Biobank’ project in the UK and US to study the interaction between genes and the environment.
13 April 2005 Gene project will map humans’ global spread (by Michael Le Page and Will Knight) Describes a project to map the migration of humans across the globe using genetic information.
19 July 2003, page 21 DIY approach to drug discovery (Rachel Nowark) Reports on a chemical genomics project that would allow academics to carry out early stages of drug development as part of existing research.
RTD info April 2005 DNA: life's memory The hundreds of millions of chemical letters in a genome sequence hold the memory of the evolution that led to a species' appearance. The skill lies in deciphering them.
Science 1 July 2005, page 80 Why do humans have so few genes? (by Elizabeth Pennisi) Explains how humans function with fewer genes than expected.
Scientific American December 2006, page 35 DNA sequencing on the cheap (Charles Choi) Reports on low cost DNA sequencing technology.
February 2006, pages 58-65 Owning the stuff of life (by Gary Stix) Covers the patenting of human genes by companies and organisations.
May 2005, pages 70-73 Molecular treasure hunt (by Gary Stix) Describes GeneWays software which reads information in scientific literature to find new molecular interactions or pathways.
April 2005, pages 40-47 Alternative genome (by Gil Ast) Explains alternative gene splicing, which allows one gene to have more than one protein or function.
October 2004, pages 30-37 The hidden genetic program of complex organisms (by John Mattick) Explains the role of junk DNA and RNA in the control of gene expression.
April 2004, pages 56-63 Evolution encoded (by Stephen Freeland and Laurence Hurst) Looks at the natural balance between maintaining the integrity of the genome while allowing mistakes for evolution.
Provides an overview of the Human Genome Project – its history, achievements to date, expected benefits and ethical issues.
About the Human Genome Project (National Human Genome Research Institute)
Includes an explanation of the Human Genome Project, the significance of the draft genome published in 2001, and a brief history of the project.
Human Genome Project information (Oak Ridge National Laboratories, USA)
Up-to-date information about a range of aspects of the project. Click on 'About the HGP' for an overview of the project and links to more detailed information. Click on 'New primer now available' for information about genomics and its impact on medicine and society. Scroll down to Project Information and Click on 'Science behind the project' for basic genetics, insights from the draft sequence and post-genome science.
Australian Broadcasting Corporation
A gene map of the human genome (US National Centre for Biotechnology)
Illustrates the genetic map for each of the human chromosomes. Several genes on each chromosome are illustrated with electron-micrographs or diagrams. There is a link to an article in Science, describing new mapping techniques in detail. A technical site.
Genetics home reference – your guide to understanding genetic conditions (National Institutes of Health, USA)
Provides information about genetic conditions and the genes or chromosomes responsible for those conditions.
Human gene testing (Beyond Discovery, National Academy of Sciences, USA)
This article explores the trail of basic research (eg, discovery of the structure of DNA, breaking the code, and mapping the DNA to locate specific genes) that opened the door to gene testing. (A PDF file of the complete article is available.)
base (in DNA). Any one of four nitrogenous (nitrogen-containing) bases (adenine, thymine, guanine and cytosine). The sequence of the bases in DNA determines the sequence of amino acids in all proteins found in living things. base pairs. Two bases held together by weak chemical bonds. The double helix shape of DNA is dependent on its two strands being held together by the bonds between the base pairs. In DNA, the bases that pair are adenine with thymine and guanine with cytosine. chromosome. A long DNA molecule that contains the genes of the organism. Chromosomes are visible in cells during cell division. DNA (deoxyribonucleic acid). The nucleic acid forming the genetic material of all organisms with the exception of some viruses which have RNA. DNA is present in the nucleus and other organelles such as mitochondria and chloroplasts. gene. The basic unit of inheritance. A gene is a segment of DNA that specifies the structure of a protein or an RNA molecule. genetic diseases. Those diseases (malfunctions) that result from abnormalities in chromosomes or DNA, and are inherited. genetic map (linkage map). A map showing the sequence of genes on chromosomes. genome. The total genetic material of an individual or species. linked. The association of traits that occurs when the genes coding for them are on the same chromosome. locus (plural loci). The position on a chromosome of a gene or other chromosome marker. map. A plan of the linear sequence of chromosomes. mapping. Constructing a plan (or map) of the linear sequence of chromosomes. physical map. A map showing the location of sites (loci) on a chromosome.
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