mirrored file at http://SaturnianCosmology.Org/ For complete access to all the files of this collection see http://SaturnianCosmology.org/search.php ========================================================== Biotechnology and Society---Part XVI Sequencing the genes Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning. -Winston Churchill (1874-1965), British statesman Midway through the Second World War, the then British prime minister spoke of the war efforts by the Allies with the words written above. The same words are now applicable to the new biology, viz., the human genome project (HGP). The year 2003 marked the end of the beginning of the project. The entire human genome has been sequenced and the data are available in a Genome Data Bank, thanks to the dedicated efforts of an international team of scientists. The new discipline of genomics (for a definition of certain terms used in this article please see Definitions at the end of the article) will change our understanding of the origin of the diseases and enable us to predict, prevent, diagnose and treat or cure them. It is a powerful tool in the drug discovery process. Click here for big picture History of HGP: HGP was begun in 1990 as a cooperative venture between the National Institutes of Health (NIH) and the Department of Energy (DOE) of the US government and culminated in 2003, two years ahead of schedule. The goals of the project were: identify some 30,000 genes in human DNA, sequence the 3 billion base-pairs, store the information properly, improve the tools for data analysis (bioinformatics), transfer the technology to private sector and address ethical, legal and social issues that might arise. The budget was $3 billion and 16 institutions participated in it. However, the bulk of the work was done by five institutions: Washington University (St. Louis), Sanger Center (UK), Baylor College of Medicine (Houston), Whitehead Institute and the DOE Joint Genome Institute operated by University of California. A working draft of the 24 chromosomes* in the human genome was published in June 2000 followed by an analysis of the genes in February 2001. While the funding by the US government took an international team of scientists, there was a simultaneous venture by a private enterprise, Celera Genomics, which employed in-house scientists and raced to finish the sequencing work independently of the public venture. The announcement and publication of the sequence was done jointly by Celera Genomics and the US government. The achievement is akin to the moon-landing venture of the 1960s. However, unlike the waning of interest in the moon due to its lifelessness, we have immense interest in the genome capped by the development of new medical applications. All diseases have a genetic component, either inherited or from the bodys responses to environmental stresses such as viruses or toxic substances. The completion of HGP enables us to identify errors that contribute to the diseases. Once the identification is done correctly, we can treat, cure, or even prevent such diseases in future. Rational drug design based on gene identification is the way to develop therapeutics. Rational drug design can also progress to pharmacogenomics to tailor the therapeutic to different patient populations. Currently, several diagnostic tests are available to indicate defective (mutated) or missing genes which cause diseases. Gene testing can progress to gene therapy to replace missing or defective genes as a remediation measure. Gene therapy is currently in a nascent state and is expected to advance towards a viable tool in the future. HGP Timeline: The HGP was done not just to sequence the human genome only. There were also other genomes sequenced along the way, such as bacteria, yeast, worms, flies and mice. We indicated in a previous article that the worm C. elegans has a gene which induces cooperative behaviour in them while a single mutation in that gene causes them to be anti-social. Understanding this and other gene characteristics among species other than humans is important in gaining knowledge that is crucial to understanding overall genetic function. The gene sequences for Mycoplasma genitalium (smallest bacterium in terms of the size of the genome), and Haemophilus influenzae were completed in 1995. In 1996 the sequence of Saccharomyces cerevisiae (the common yeast) was published, followed by that of Escherichia coli (the bacteria in the gut) in 1997. The year 1998 saw the completion of the gene sequences of C. elegans (a tiny worm), and that of Mycobacterium tuberculosis (an organism which causes tuberculosis as the name implies). The complete sequence of chromosome No 22 was published in 1999. The year 2000 witnessed the completion of the gene sequence of Drosophila melanogaster (the fruit fly) as well as the working draft of the entire human genome. Several other chromosomes were sequenced in the ensuing period. With the determination of the remaining chromosomes in 2003, the HGP was completed in April 2003. In addition to the sequencing work, new technologies for synthesis of genes, separation of DNA and computational methods were developed as part of the project. Click here for big picture The human genome has 3.12 billion base pairs (~30,000 genes). It is an enormous number. But let us take note that the genomes of certain plants like trumpet lily (90 billion base pairs), and corn (5 billion base pairs and 50,000 genes), certain amphibians, some fish like marbled lungfish (139 billion base pairs), the warty newt (18.6 billion base pairs), and salamander (50 billion base pairs) are bigger (be not proud, man!) than the human genome (see figure), although most of the DNA in all the species is without any function (called junk DNA) but just a carryover. Who said Nature is efficient? Humans use only 2 or 3 times as many genes (~30,000) as the simple worm and 5-10 times as the simplest microbe. The pinnacle of the evolutionary pyramid must clearly be due to a complicated architecture of the regulatory network of genes in the human genome. *The human haploid genome contains 23 chromosomes, of which 22 are autosomes common for both female and male. The two sex chromosomes are called X and Y. The egg cell contains only the X chromosome while the sperm cell contains either X or Y. Every somatic cell (other than germ cells) in the human body contains 46 chromosomes (22 autosomes from each of the parents and a pair of either X-X (female) or X-Y (male). Since there are two sets of the 22 chromosomes, it is enough to sequence only one set of 22 chromosomes, and the two sex chromosomes, X, and Y, amounting to a total of 24 chromosomes to be sequenced. Definitions: Autosome: Any chromosome other than sex chromosome. Gene: An ordered sequence of nucleotides located in a particular position on a particular chromosome that encodes specific functional product such as an enzyme, protein, or RNA molecule. Gene sequencing: Determination of the order in which the nucleotides are strung together in a gene. Genome: All the genetic material in the chromosomes of a particular organism. The size is given as its total number of base pairs (nucleotides). Genomics: The study of genes and their functions. Genotype: The genetic characteristics or description of an organism defined by the nucleotide sequence of the genome. Haploid: A cell with half the usual number of chromosomes or only one chromosome set. In the humans it would be 23 chromosomes. Sperm cells and egg cells are haploid. Pharmacogenomics: The science of understanding the correlation between an individual patients genetic make-up (genotype) and his/her response to drug treatment. The efficacy of a given drug could vary between different patient populations depending on the genotype. Profile of the author Dr. Sethuraman Subramanian subramaniansethu at hotmail.com Published on 25^th Feb, 2004 Copyright © 2005, Chennai Interactive Business Services (P) Ltd. All rights reserved.