Phenotypic traits and

Association studies are used to identify common alleles more frequently associated with phenotypic traits such as drug response or ADRs. These associated alleles are called causal polymorphisms or functional polymorphisms and are risk-conferring factors of the trait at the population level, while, at the individual level, they impact either on the cellular level of the gene product or its function. 

A powerful approach to elucidating the ecology and evolution of any phenotypic trait can come from an explicit manipulation of genetic differences in the trait among populations of a single species, a research focus of evolutionary ecologists... 

Different molecular identification methods have been described and used for differentiation of the three phenotypically similar species (S. cerevisiae, S. uvarum, and S. bayanus). These include karyotyping, PCR-RFLP of the METZ gene, and microsatellite multilocus typing. None of them seem to be perfect alone, and some phenotypic traits need to be assessed for clear distinction (Antunovics et ah, 2005). 

Masneuf-Pomarede, I., Bely, M., Marullo, P., Lonvaud-Funel, A., and Dubourdieu, D. (2010). Reassessment of phenotypic traits for Saccharomyces bayanus var. uvarum wine yeast strains. Int.. Food Microbiol. 139,79-86. 

The major advantage of (fractional) oral clearance as a phenotypic trait is that its value is linearly related to the enzyme s catalytic activity, provided that first-order conditions are present. This requirement, along with any safety considerations, is the main reason the dose of an in vivo probe should be as low as possible, consistent with analytical considerations. Furthermore, it is possible to directly extrapolate this type of trait measure to the disposition of other drugs whose metabolism is mediated by the measured enzyme and also to place the trait value within a therapeutic context. On the other hand, estimation of oral clearance requires multiple blood and urine collections, often over many hours, that are an inconvenience for the study subject and require considerable amounts of analytical time and effort. Because of this, simpler and less time-consuming approaches have often been used. However, it is not always appreciated that such phenotyping tests provide only an indirect measure of metabolizing activity and may be affected by factors other than the enzyme s intrinsic clearance. In addition, it is difficult to relate an indirect trait measure to parameters that are of clinical importance, such as the drug s clearance. 

Following the in vitro discovery that a particular metabolic pathway is mediated by a single CYP isoform and that such metabolism is a major route of elimination, it is not uncommon to speculate that appropriate assessment of the formation of the metabolite in vivo could serve as a phenotypic trait measure (see Chaps. 3 and 7). Moreover, knowledge of the disposition of the drug and metabolite may indicate a putative quantitative trait for this purpose, e.g., urinary MR. However, considerably greater effort and information is, in fact, required before such a trait value can be accepted as a valid measure of the enzyme s metabolic activity. Unfortunately, several of the earlier-developed in vivo probes were not rigorously evaluated prior to their application, and interpretation of differences/changes in their trait values is therefore not easy. 

---