DNA Sequence and Chromosome Organization

The massive human genome project should achieve its goal of determining the complete sequence of human and mouse genomes in the near future; a “rough draft” has already been obtained. Furthermore, this genome initiative, pursued by both government and private enterprises in the United States and other countries, has already culminated in elucidating the complete sequence of E. coli and other bacteria, as well as yeast, a nematode, and the fruitfly Drosophila melanogaste. Significant progress has been made in elucidating the nucleotide sequences of both human and mouse genomes by using a two-pronged approach. On one hand, the sequences of transcribed regions of the genomes are being deduced from sequences of randomly isolated mRNA segments reverse transcribed into DNAs. At the same time, complete DNA sequences of fragments of whole chromosomes are being directly determined. This has opened up a huge scientific challenge of deciphering the genetic information, identifying unknown genes and their encoded proteins, and the variability of gene sequences with corresponding changes in the protein sequences in individuals. Functional genomics is a newly created discipline which deals with the deterministic prediction of protein functions from the primary sequences. One extension of such analysis is to ascertain the consequences of allelic polymorphisms in the human genome, i.e., minor changes in the sequences of cellular proteins which do not cause an explicit pathological phenotype and yet may affect survival and predisposition to specific diseases in the long term.

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