Genome Project,Human Chromosomes,Mapping,Strategy of Genome,Functional Analysis,Gene Function,Chromosome Region,Analysis of cDNA Clones

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	Genome Project This is an undertaking by many countries (currently administered jointly by the National Institute of Health and Department of Energy, U.S.A.) to acquire "complete knowledge of the organisation, structure, and function of the human genome". It is aimed at finding out all the genes in each of the human chromosomes (and ultimately of other organisms) to determine their function, and, hopefully, to understand how they together form the complete organism.
The human genome project began on Oct. 1, 1990. This is regarded as the most ambitious project ever undertaken by man. The strategy of genome project may be grouped into the following three stages: (1) mapping, (2) sequencing and (3) functional analysis Mapping The first major goal of the project is to prepare high resolution or saturated genetic and physical maps of human genome (and genomes of other experimental organisms). Molecular markers have been used to produce maps of all the human chromosomes in which markers are located only a few cM apart.
By August, 2000, over 9,300 markers had been mapped to particular chromosomes. Therefore, any new DNA sequence (i.e., an additional marker) can be easily linked with these markers. Sequencing. The DNA fragments used for sequencing are generally obtained by the "shot gun approach", in which DNA fragments generated from a given source, e.g., whole genomic DNA, a YAC, or a cosmid clone, are cloned and sequenced at random. As a result, a DNA fragment is ordinarily sequenced more than once, and the various fragments sequenced belong to random locations in the DNA source. Therefore, integrating the sequence data into the correct order to obtain the sequence of the entire DNA molecule is a prohibitive task even with the enormous computer capabilities available at the moment.
Another approach to sequencing is to create a series of contigs before sequencing. A contig consists of a series of recombinant clones that contain overlapping DNA inserts covering a specific region of a chromosome or even a chromosome. The member clones of a contig are sequenced individually and aligned properly to yield the sequence of the concerned chromosome/chromosome region. The approach facilitates proper alignment of sequenced pieces but creation of contigs itself is time consuming. Both these approaches have been successfully used to sequence the human genome. The draft sequence of human genome was published in June, 2000. As on April, 2003, about 99% of the euchromatic part of human genome had been sequenced with 99.9% accuracy.
	Functional Analysis. The ultimate objective of the genome project is to decipher the function of each of the 40,000 or so genes estimated to be present in the human genome. This is the most challenging task and may take several decades. There are three general approaches for the functional analysis: (1) analysis of cDNA clones from specific tissues, e.g., brain; each cDNA clone is sequenced only for a short region which provides an STS (expressed sequence tag, EST) for the concerned gene as well as enough base sequence data to decide if the gene is new or already known. This way, it should be possible to determine the tissue-specific and ubiquitous (functional in all tissues) genes, and also to map these genes. (2) The sequence data may be analysed using a computer to identify the genes present in the genome. Finally, (3) The gene function has to be determined by studying the effects of mutation; extensive mutant libraries are being created for this purpose.