What Is Phenotyping and Why Is It Important?

Although the concepts were expressed by Mendel decades earlier, the terms “gene”, “genotype” and “phenotype” were introduced by the Danish botanist Wilhelm Johannsen in 1909. Gene is from the Greek genos (race or offspring), and refers to a unit of heredity. Genotype is from the Greek genos and tupos (type)?and refers to?the genetic constitution of an individual organism. Phenotype is from the Greek phainen (to show) and tupos (type) and refers to the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment; thus phenotypes reflect the nature and the nurture of the organism. (Wanscher 1975; Mayr 1982; Henig 2001, Jewell 2001)

Genome projects for organisms as diverse as viruses, yeasts, worms, mice, men and elephants have made great progress in determining the nucleic acid sequences of the genetic material, or genome, of various species. Within each organism’s genome are functional genes (nucleic acid sequences that encode protein gene products), as well as long regions that seem to have no product or function.

While genome projects continue to provide crucial information about the structure of genomes and their genes, functional genomics (or functional genetics) initiatives strive to understand the function of genomes and their genes. Identification of a protein gene product and determination of its function as a receptor, ligand, or enzyme is a proximal goal. Understanding the role of the gene and its product in the context of a living organism is the ultimate goal. Thus, functional genomics efforts in genetically engineered animals aim to produce and characterize phenotypes that clearly result from the intended genetic manipulations and help to elucidate gene functions. However, phenotypes reflect genetic influences other than the intended genetic manipulations, as well as experiential and environmental influences including infectious agents. Potential impacts of extra-experimental variables must be considered when interpreting phenotype data.

Phenotyping evaluations can combine in vivo evaluations, imaging strategies, and clinical and anatomic pathology to characterize complex phenotypes, including multisystemic phenotypes or syndromes, to develop and validate Genetically Engineered Mouse (GEM) models, and can apply these same resources to almost any area of preclinical translational research.

Institutional and individual phenotyping strategies necessarily reflect local resources, and Johns Hopkins is fortunate to have outstanding resources. The Department of Molecular and Comparative Pathobiology and its training program are unique among research institutions in terms of the breadth and depth of comparative medicine and pathology expertise that we have available to contribute to phenotyping and other pre-clinical translational research efforts.