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Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000.

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An Introduction to Genetic Analysis. 7th edition.

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Genomics: an overview

Genomics is divided into two basic areas: structural genomics, characterizing the physical nature of whole genomes; and functional genomics, characterizing the transcriptome (the entire range of transcripts produced by a given organism) and the proteome (the entire array of encoded proteins).

The prime directive of structural genomic analysis is the complete and accurate elucidation of the DNA sequence of a representative haploid genome of a given species. When this sequence is known, it opens the door to numerous possibilities. By computational analysis of the sequence, using principles developed by genetic and molecular biological analysis of transcripts and proteins, we can make predictions of all of the encoded proteins. We can analyze other haploid genomes from the same species and develop a statistical picture of the genetic variation within populations of that species. We can compare the genomic sequence of different species and thereby gain an understanding of how the genome has been remodeled in the course of evolution. Studies of comparative genomics have already proceeded far enough to reveal that, in related species (for example, within all mammals), there is considerable synteny (conserved gene location within large blocks of the genome). Studies of comparative genomics also offer a powerful opportunity to identify highly conserved and therefore functionally important sequence motifs in coding and noncoding genomic DNA. This identification helps researchers confirm predictions of protein-coding regions of the genome and identify important regulatory elements within DNA.

Even though structural genomics is only a little more than a decade old and is already fulfilling the promise of providing complete sequences of many genomes, the leap from classical genetic maps to complete DNA sequence maps did not happen in a single bound. Rather, quite analogous to the way in which one proceeds through several increases in magnification on a light microscope, there was a step-by-step progression in genome-wide map resolution in the development of genomic technologies. In this chapter, we will focus considerable attention on the development of high-resolution genetic and physical mapping technologies that ultimately permitted sequencing of complex genomes. Not only were these technologies invaluable steps on the way to the establishment of sequence-level maps, but they also proved to be extremely important tools in themselves for disease-gene identification and positional cloning.

It quickly became apparent that the availability of completely sequenced genomes merely whetted the scientific appetite for additional global information. In particular, turning the “Rosetta stone” of genomic sequence into rigorous predictions of transcript and protein sequence proved to be a challenge in itself, and so projects to directly characterize the structures and sequences of all RNAs and all polypeptides have evolved. These projects have formed the foundation of functional genomics. Typically, transcript structures have been characterized by sequencing full-length cDNAs (see Chapters 12 and 13) and comparing these sequences with those of the corresponding genomic DNA. As we will see toward the end of this chapter, the availability of these cDNA sequences has permitted the development of very dense microspot arrays in which each microspot represents a different mRNA. These microspot arrays, constituting an entire transcriptome, can be kept on a single microscope slide and can then be probed by hybridization for the concentrations of transcripts in a given cell type under a given set of environmental conditions. These hybridization experiments permit the assay of literally hundreds of thousands of data points in a single afternoon and provide global information on how a given condition perturbates gene activities in a systematic way.

Similar to approaches used for the transcriptome, ways to systematically and globally identify the proteome (that is, all proteins that a species can produce) are under development. Because, as we shall see later in the book (Chapter 23), many biological decision-making processes require protein modifications and changes in protein–protein interactions, understanding the proteome (and the transcriptome for that matter) is just as important as understanding the genome.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, W. H. Freeman and Company.
Bookshelf ID: NBK21974

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