Question

Disease: Phenyketonuria

Describe the relationship between the disease phenotype (i.e., symptoms) and the

different genotypes with the disease-causing allele. In your description use the terms:

homozygous, heterozygous, dominant/dominance, and recessive.  *Note: this will look

different if your disease is sex-linked!

a.    Next, write out these different genotypes using capital letters for dominant

alleles, and lower-case letters for recessive alleles.

Answer 1

Answer: It is a metabolic disorder. Mutations in the PAH gene (Phenylalanine hydroxylase) cause phenylketonuria. The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase which located on Chromosome 12.

Phenylketonuria (PKU) is a rare genetic condition that causes an amino acid called phenylalanine to build up in the body. Phenylalanine hydroxylase is an enzyme your body uses to convert phenylalanine into tyrosine, which your body needs to create neurotransmitters such as epinephrine, norepinephrine, and dopamine. PKU is caused by a defect in the gene that helps create phenylalanine hydroxylase. When this enzyme is missing, your body can’t break down phenylalanine. This causes a buildup of phenylalanine in your body.

Symptoms:

PKU symptoms can range from mild to severe. The most severe form of this disorder is known as classic PKU. An infant with classic PKU may appear normal for the first few months of their life. If the baby isn’t treated for PKU during this time, they’ll start to develop the following symptoms: Seizures (changes in the brain’s electrical activity), stunted growth, hyperactivity, a musty odor of their breath, skin, or urine. A less severe form of PKU is called variant PKU or non-PKU hyperphenylalaninemia. This occurs when the baby has too much phenylalanine in their body. Infants with this form of the disorder may have only mild symptoms, but they’ll need to follow a special diet to prevent intellectual disabilities.

Genetics: It is an autosomal recessive inheritance. PAH encoding gene located on autosomes. PAH gene represented by two alleles. One is Dominant allele: Which can express in both homozygous and heterozygous condition. It represented with "P".  Recessive allele: Which can express in only in homozygous condition. Which represented with"p".

Homozygous: Two alleles are similar, each allele present on two homologous chromosomes each is called homozygous ex: PP or pp.

Heterozygous: On homologous chromosomes, One allele is dominant and another is recessive. (Eg: Pp).

a) Genotype with respect to PAH gene:

PP: Homozygous dominant. The individual is healthy. No PKU.

Pp: Heterozygous dominant. The individual is a carrier. Not observing the PKU symptoms. Next generation may be affected with PKU.

pp: Homozygous recessive. 100% individuals suffered from PKU, irrespective of the sex of progeny (either male or female). Because it is the autosomal recessive disorder.