Many times in class we said that P = G x E. And yet, what we mean by \"environme
ID: 169113 • Letter: M
Question
Many times in class we said that P = G x E.
And yet, what we mean by "environmental effects" is often slightly misunderstood.
Phenolketonuria (PKU) is a recessive condition that can cause brain damage in affected children. But if PKU-affected children are placed on a phenylalanine-low diet, they do fine. For this reason, we say that PKU is a condition (phenotype) that is under strong environmental influence or effect (in this case the environmental factor is the diet, of course).
However, using molecular biology techniques, we can see that the enzyme that causes PKU is expressed at the same levels in children on a normal or Phenylalanine-low diet. So, how can we say that "PKU is a genetic condition under strong environmental influence" when the environment does not influence the expression of the allele (gene) underlying this condition...?
Explain in 100 words or fewer.
Explanation / Answer
Phenylketonuria is an inheritance disease predominantly autosomal recessive genetic disorder associated with impaired metabolism of phenylalanine due to mutation in chromosome 12 that could be homozygous or compound heterozygous mutations within the chromosomal gene that enable to synthesize enzyme to metabolize hepatic phenylalanine that is phenylalanine hydroxylase (PAH). Environmental factors such as limiting protein intake, diet can assist in relieving hyperammonemia (a major abnormality in PKU) because low protein diet has low phenylanalnine synthesis with no effect on "gene expression coding for PAH" as a result high pheylalanine will be eliminated easily even in the absence of PAH. Therefore, PKU is a genetic condition under strong environmental influence" when the environment does not influence the expression of the allele (gene) underlying this condition. Therefore, optimum low protein diet is crucial as per doctor guidelines for PKU treatment
Normally, during PKU, phenylalanine hydroxylase (PAH) is very important measure of phenylketonuria as it can convert excess phenyalanine into metabolite and reduce the accumulation of phenylalanine thereby PAH enable to reduce phenylketonuria.
Phenylalanine hydroxylase (PAH) mutants are due to single nucleotide base change mutation leading to synthesis of truncated enzymatic protein from mRNA transcript due to base exchange and this is called tautamerization (keto to enol form of bases). The truncated enzymatic proteins often produce changed kinetic behavior with decreased stability thereby finally result in, catalytic modification of the enzyme due to tetramerization domains of the enzyme