What is Phenotyping?
Phenotyping for functional genomics initiatives – What does this mean 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 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 have provided and continue to provide crucial information about the structure of genomes and their genes, functional genomics 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 in the process. Understanding the role of the gene and its product in the context of a living organism in its environment is the ultimate goal of functional genomics initiatives. Thus, functional genomics efforts in genetically engineered animals aim to produce and characterize phenotype(s) that clearly result from the intended genetic manipulation(s) and help to elucidate gene function(s). 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.
A tiered phenotyping approach consists of an initial (1st tier) comprehensive evaluation, followed by more focused or targeted evaluations. Selection of 2nd tier and subsequent tests is based on information derived from initial evaluations. The objective is to combine in vivo evaluations, imaging strategies, and clinical and anatomic pathology to characterize complex phenotypes, including multisystemic phenotypes or syndromes, and to develop and validate Genetically Engineered Mouse (GEM) models.
Institutional and individual phenotyping strategies necessarily reflect local resources, and Johns Hopkins is fortunate to have outstanding resources. DCM and its training program are unique among research institutions in terms of the breadth and depth of comparative medicine and pathology expertise that can contribute to phenotyping efforts.
