Phenotype complexity

The phenotypic complexity noted for other GCPR diseases is true also for PTHRl mutations. Opposite clinical manifestations have been reported to result from distinct recessive mutations in the gene. These rare variants present as Eiken syndrome, a distinct entity from JMC and Blomstrand s chondrodysplasia and from enchondromatosis. The skeletal features are opposite those in Blomstrand s chondrodysplasia. The Eiken syndrome variant, resulting in a truncation at position 485, may result in a paradoxical phenotype caused by the consequences of disrupting the carboxyl tail of the receptor (60). 

Biological targets may consist of single-entity proteins, complexes of receptors (dimers), or receptors plus accessory proteins. Mixtures of gene products can produce unique phenotypic biological targets. 

As well as complex biological targets, complex chemical targets (drugs with multiple activity, prodrugs) can be used to produce therapeutically useful phenotypic responses. 

As pharmacogenetics and pharmacogenomics are not mutually exclusive, but even sometimes display overlapping features, both disciplines are aimed at better tailoring medical therapy for a given complex disease such as essential hypertension or other CVD. In the wake of new technologies to identify candidate region for whatever phenotype, more robust and complex bioinformatic analyses are necessary to... 

The situation is somewhat more complex for virus sample amphfied or isolated directly from patient plasma, as these samples comprise a heterologous mix of related yet genetically distinct quasi-species. Often these samples contain mixtures of CCR5-tropic (R5), CXCR4-tropic (X4), and/or dual-tropic viruses these samples are classified in phenotypic ttopism assays as dual/mixed tropic (D/M) (Whitcomb etal. 2007). 

Certain mutant hemoglobins are common in many populations, and a patient may inherit more than one type. Hemoglobin disorders thus present a complex pattern of clinical phenotypes. The use of DNA probes for their diagnosis is considered in Chapter 40. 

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