HUMAN GENOME PROJECT

                   As the recombinant DNA, gene cloning and DNA sequencing technologies improved in the 1970s and early 1980s the scientists because more and more bold and ambitious and they began to think about the possibility of sequencing the entire human genome which is about 3x10⁹nucleotide pairs at an estimated cost of $ 3 billion. this gave birth to the Human Genome Project in 1990 with Dr. James, D. Watson as its first director. 

                  As of now, the completed nucleotide sequences of the geneomes of 599 viruses, nucleotide  viroids, 205 plasmids, 185 organelles viz. chloroplast and mitochondria, 32 true bacteria, 7 archaea, a fungus, plant, a worm and a fly have already been determined. Incidentally, in 1995, the entire genome sequence of the first bacterium. Haemophilus influenza was reported. This project stimulated similar mapping and sequencing projects on the genomes of several other organisms viz. E-coli (bacterium), S. cerevisiae (yeast), D. melanogaster (fruitfly), A. thaliana (a plant) and C. elegans (a worm).

                    The Human Genome Project, a giant leap in the field of genomics was also a very formidable task. soon, the scientists realised the enormity of this task, which involved mapping of at least 1,00,000 genes and sequencing an estimated 3 billion nucleotide pairs. This necessitated a coordinated as well as an international effort and hence International Human Genome Organization (HGO) was established. this involves an international publically funded consortium of scientists at Universities and research institutions with 20 large sequencing centres in six countries like USA, Germany, France, Japan, England and Switzerland with China joining later, plus a number of other labs working on small projects.

                     Initially, the project envisaged (i) to map all human genes (ii) to construct a physical map of the entire human genome, and (iii) to determine the nucleotide sequence of all the 24 human chromosomes. But, soon the project became very ambitious with the competition hotting up every day.

                  Dr. Craig Venter, who is often considered to be synonymous with this project, because of his enormous contribution to this field, set up an institute, The Genomic Research (TIGR) in  Rockville, Maryland. He later (1998) teamed up with Perkin Elmer Inc. of Norwalk, Connecticut, to form a new private company, Cellera Genomics for funding and commercial exploitation of this research. Venter stunned the genomics community by announcing the sequencing of human genome in just 3 years! His proposal was based on 

two key developments:

(1) A sequencing strategy  called whole-genome shotgun sequencing ; and

(2) The development of faster, fully automated sequencing machine.


               In October, 1998, Francis Collins and colleagues,  another key player in the race to sequence human genome  and Director of Human Genome Project (HGP) announced the completion of the project by 2003- two years earlier than originally planned! they proposed a working draft of human genome with at least 90 % sequenced with 99% accuracy by 2001.

                This "healthy" competition hastened the progress of both the groups and they achieved their initial goals  goals much ahead of schedule. 

                  On February 15, 2001, the public International Human Genome Sequencing Consortium (IHGSC) published their first draft of the sequence of the human genome in Nature (covering˜92% of the sequence of the genome with 150,000 gaps). On February 16, 2001, a day later, the private Celera Genomics group published their first draft in Since covering (˜95%) of the sequence of euchromatic DNA. Since the, both the groups have not looked back and the race goes on!

(1) The small number of genes in the human genome (˜30,000), although based on the approximate ratio of the size of a typical gene (˜ 3x10₄ bp) to the size human genome (3x 10₉bp), it was earlier estimated that there might be 1, 00,000 genes in human. This is because 50% of the genome comprises of non-coding sequence (or "junk" DNA ) and only less than 5% accounts for coding sequences.

(2) Proteomes (or full set of proteins )coded by human genome are very complex.
(3) Exons make up eary 1.1% of the genome whereas intros make up 24% and 75% of the genome is intergenic.

                  The initial draft of the human genome is far from complete and concerted efforts since then by both the groups have led to the near competition of Human Genome Project in 2003. Although it's still incomplete with 308 euchromatic gaps and heterochomatic genomes is yet to be deciphered!

• IHGSC reported the completion of eurchromatic sequence in October, 2004 with only 341 gaps (as against 1,50,000 gaps reported in the first draft), with 308 euchromatic and 33 heterochromatic gaps
• The total number of estimated protein coding genes are also reduced to 20,000 -25,000 with 19,599 confirmed genes (equal to total number of genes of tiny round worm Coenorhabitis elegans).
• Completion of DNA sequencing of chromosome 1 (largest among human chromosome comprises nearly 8% of all human genetic information and is associated with over 350 human diseases including cancer, Parkinson's disease, Alzhheimer's diseases, etc.

Exons - are segment of DNA that are transcribed ito mRNA and then translated into proteins.

Introns- Portion of mRNA that is removed by enzymes before the mature RNA is translated into proteins.