Somatic mosaicism and variable expressivity

For more than 50 years geneticists have assumed that variations in phenotyp ic expression are caused by alterations in genotype. Recent evidence shows that 'simple' mendelian disorders or monogenic traits are often far from si mple, exhibiting phenotypic variation (variable expressivity) that cannot b e explained entirely by a gene or allelic alteration. In certain cases of a ndrogen insensitivity syndrome caused by identical mutations in the androge n receptor gene, phenotypic variability is caused by somatic mosaicism, tha t is, somatic mutations that occur only in certain androgen-sensitive cells . Recently, more than 30 other genetic conditions that exhibit variable exp ressivity have been linked to somatic mosaicism. Somatic mutations have als o been identified in diseases such as prostate and colorectal cancer. There fore, the concept of somatic mutations and mosaicism is likely to have far reaching consequences for genetics, in particular in areas such as genetic counseling.