SUMMARY

The sequencing of the human genome and a variety of animal genomes will provide fundamental information about genome organization, genome evolution, gene sequence variety, and genetic polymorphisms. Sequencing will also provide a platform for global systematic analysis of gene function and gene expression. Developmental toxicology and risk assessment are expected to benefit in major ways from the new methodologies and information, namely, in the analysis of gene-environment interactions in human development defects and in the analysis of toxicant action on developmental processes.

A quarter to a half of the human developmental defects are believed to be attributed to interactions of the genotype and environment—that is, the exposure of individuals of a particular genetic composition to particular environmental conditions to which they are more sensitive than are others. Complex gene-environment interactions present a great challenge to developmental toxicology. The best epidemiological methods, the most discriminating molecular assessments of exposure and effect, and the most detailed analysis of genetic differences will be needed to make progress in understanding gene-environment interactions. Recent improvements in high-throughput sequencing of the human genome and in the identification of polymorphic markers conveniently spaced along each chromosome increase the chances for progress in this direction. Within this new area of molecular epidemiology, recent insights into human differences in activity levels of various DMEs and the genetic basis for those differences, offer great promise. Other kinds of gene products that might be important in susceptibility but are less well known, include components of developmental processes, particularly the components of signal transduction pathways and genetic regulatory circuits. These components will be discussed in later chapters.

Methods now are available to describe patterns of simultaneous expression of thousands of genes of developing cells and tissues and, in principle, to describe the changes of expression in the embryos of normal experimental animals and those following testing with toxicants. The use of such methods is expected to improve the categorization and analysis of toxicant-induced developmental defects.

The amount of data generated by modern genomic methods is prodigious. For the full benefit of the data, departments or divisions of bioinformatics in universities and industries will be needed to keep track of the data and to analyze it with respect to questions about genome organization and function.



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