Genotype–Phenotype Correlations: Filling the Void

[摘要] Classical Mendelian genetics often conjure the image of a well-defined mutation in the DNA sequence that causes a disruption in gene function and characteristic phenotype. However, Mendelian traits can often behave like complex disease traits. One level of complexity is that even a specific mutation may be associated with a wide spectrum of symptoms, with expression perhaps modified by the effects of other genes and/or environmental factors. Another source of phenotypic variation can arise from the fact that there may be multiple functional mutations in the same gene, each associated with its own set of symptoms depending on the effects of the mutation on altering gene product or function. For example, depending on the mutation type, there may be either total or partial loss or gain of function. In addition, many genes have multiple isoforms. Under this premise, the location and consequence of the mutation can differentially affect the various isoforms, resulting in variable aberrations of multiple gene products. This mutational diversity has limited our ability to diagnose diseases with primarily genetic causes, as well as to predict their natural histories.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome