Genetic testing and genotype–phenotype correlations

Abstract

Abstract In the postgenome era, the study of genotype–phenotype correlations has come to the front. Insight into genotype–phenotype correlations would move clinical genetics toward predictive medicine. However, it has become clear that the correlation between genotype and phenotype is often incomplete. The frequent lack of correlations supports the notion that a mutant gene product is part of a complex system in which tissue‐specific alternative splicing, intragenic SNPs, epigenetic changes, protein–gene and protein–protein interactions, modifying genes, and environmental factors play a role. The insight that “simple” Mendelian traits are in fact complex traits has consequences for families and their physicians, and is a challenge for the scientific community. Hence, there is a strong clinical and scientific motivation to identify factors playing a role in genotype–phenotype correlations. Examples of diseases and disease genes where genotype–phenotype correlations have been observed to some extent are described below.