Gene and Environment

Phenylketonuria (PKU) is a classic example of gene-environment interaction. PKU was originally described as an autosomal recessive metabolic disease, in which people with two defective copies of the phenylalanine hydroxylase gene are unable to convert phenylalanine into tyrosine. This inability leads to an accumulation of phenylalanine in the blood, causing problems with nerve and brain development that result in mental retardation.

The treatment of PKU by removing foods containing phenylalanine from the diet (and thus reducing the accumulation of phenylalanine) demonstrated that mutations in the phenylalanine hydroxylase gene cause mental retardation only in the presence of dietary phenylalanine. Since phenylalanine is very common in the diet, this gene-environment interaction was not detected at first. PKU serves as an illustration that phenotypes that are apparently Mendelian in nature may have complex interactions with other genes and with the environment. Removing the exposure to dietary phenylalanine prevents mental retardation, and phenylalanine does not cause mental retardation in the absence of mutations in the phenylalanine hydroxylase gene. Therefore, both factors are needed to cause mental retardation due to PKU.

The identification of the gene-environment interaction in PKU has led to the effective treatment of this genetic disorder. Individuals who carry mutations in the phenylalanine hydroxylase gene, if placed on a lowphenylalanine diet, generally do not develop the symptoms of PKU. To identify individuals at risk of PKU, newborns are screened for elevated phenylalanine levels in the blood. Those infants with positive screening tests are then evaluated further. Those with PKU (about 1 in 10,000 live births) are then placed on low-phenylalanine diets to prevent the development of mental retardation.