Physiological genomics: tools and concepts

Physiological genomics is an emerging field that brings together the disciplines of genomics and cell, organ and whole animal systems integrative physiology in an effort to attach function to the DNA sequences of complex living systems. The term ‘genomics’ was coined in the early 1990s to describe the innovative high-throughput sequencing technologies and computational approaches that enabled the study of an organism's DNA in the full haploid set of chromosomes, rather than the study of a single gene or a family of functionally or structurally related genes. Thus the term ‘physiological genomics’ was applied to research that was directed toward an understanding of the relationship of genes to complex physiological functions.

As the ever-efficient parallel sequencing approaches began to elucidate the sequences of many different complex organisms, scientists from both the genomic and physiology communities recognized the great challenges as well as great opportunities now facing them as they pondered on how to attach function to the seemingly endless genomic sequences. The following series of brief reviews represent six areas of research that have been at the forefront of these efforts in the immediate postgenome period.

These include:

1. Identifying genes and genetic variation underlying complex physiological traits and human diseases by recombination mapping and complex phenotyping using inbred animal models (McBride et al. 2003) and human populations (Broeckel & Schork, 2003).

2. Use of chromosomal substitution techniques in inbred animal models to identify genes of complex physiological pathways and disease (Cowley et al. 2003).

3. The creation and use of large-scale mutagenesis in mice to identify novel functions for genes and novel genetic pathways (O'Brien & Frankel, 2003).

4. Cloning techniques that enable nuclear reprogramming and the asexual reproduction of an individual embryonic stem (ES) cell nuclear transfer (Mullins et al. 2003).

5. The application of high-throughput gene expression profiling and analytical techniques that can be used by physiologists to achieve a multidimensional integration of physiology (Liang et al. 2003).

6. The use of comparative sequence-based studies to provide biological insights derived from comparative (Nobrega & Pennacchio, 2003).

Much of what has been published over the past four years in a variety of journals reflects the nature of genomics, that is large-scale data sets. It is imperative that if physiologists are going to utilize the tools of these accomplishments of ‘big science’ that they must now lead the way in merging high-throughput data sources and hypothesis-driven research into a cohesive picture of cell, tissue and whole organism function. I appreciate the excellent contributions made by each of the invited authors that provided current and concisely written reviews from each of their respective areas of research. I believe they strongly reflect some of the important areas of research in physiological genomics at this time and point the way to future work in this field.