In this, the final chapter of this book, we have come full circle. The major themes that we promised we would cover have been woven throughout the chapters. To complete this process we will revisit and expand on several important themes:
Unity and diversity: the genetic continuity of life as evidenced in model organisms.
Genetic and etiological heterogeneity
Genotype × phenotype associations
Pathogenesis: how do changes in DNA translate into disease?
The Human Genome Project and developing fields like proteomics give us unprecedented detail about the primary products of genetic coding. But we have seen how hard it often is to relate protein-coding genes to phenotypes, because of posttranslational processing and other events. Studies of model organisms can help direct our understanding of this complexity. In the next section, we will describe some of the experimental advantages of a select group of model genetic organisms and identify some of the key insights that have so far come from work with them.
This chapter will, therefore, be organized a little differently than the ones before it. We begin with Drosophila, not because it is the simplest, but because it is one of the first and most influential non-vertebrate models of genetic organization and function. Other important model organisms will then be introduced. We will discuss different mechanisms of pathogenesis.
Finally, we will see how advances in medical genetics promise to continue altering the face of medicine and the treatment of human genetic conditions.
Part 1: Bacteria, Fruit Flies, Mice, Fish: The Value of Model Organisms
The common fruit fly was one of the first organisms used to explore the mechanisms of inheritance. It became a model for the study of transmission genetics. In fact, some of the genetic insights from work with Drosophila are so fundamental that it is easy to take them for granted. But research with model organisms has continued to add dramatically to understanding our own genetics and development. A model organism offers some advantages—a known or small genome, simple develop, or easy rearing for mating studies and identification of mutations. Escherichia coli, yeast, round worms, and even simple plants allow us to see into the common genetic processes that are shared by all forms of life.
Most of the important discoveries that are the foundation of medical genetics could not have been made in humans. Fundamental genetic mechanisms often require large numbers of replications, controlled genotypes and environments, experimental manipulation of the genome or the developmental pathways each controls, and the use of tools like mutagenesis. Even when not outright illegal, these would be far too complex and time-consuming to apply to human families and populations. Thus, to ignore the contributions that model organisms have made to understanding human genetics is very shortsighted. Simple animals allow us to study in depth the ...