INSTRUCTIONS
Go to the OMIM database on the NCI portal. Search for PAH, select the first record on the list The following page will appear: Read the initial information Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of the enzyme PAH (Phenylalanine Hydroxylase). Lack of PAH enzyme activity results in elevated level of phenylalanine. On the other hand, mutations in the PAH gene can also result in a milder disease called hyperphenylalaninemia (HPA) characterized by an elevated level of phenylalanine without the cognitive impairment associated with PKU. QUESTIONS
Question 1: Consider two actual DNA mutations found as 2 PAH mutant alleles. a. Mutation # 0017 changes codon 414 from a tyrosine to a cysteine (TYR414CYS). A homozygous genotype leads to HPA. Indicate the type of mutation for 0017 at the DNA level. Identify the class of mutation at the protein level. Based on the disease phenotype, would you expect the mutated protein to be partially functional or non-functional? (I think it is functional..? http://www.omim.org/entry/612349) Explain your reasoning briefly b. . Mutation #0018 is a mutation that changes the splice site of intron 4 (IVS4). Explain the consequence of mutation 0018 at the level of transcription of the gene, splicing and protein synthesis. Homozygous 0018 leads to PKU phenotype Question 3: Assume an individual heterozygote for 0017/0018. ?Which special term is used to describe a heterozygote with two different mutant alleles - Compound heterozygote Where along the dominance-recessivity scale would the phenotype of this individual falls in relation to the phenotype of the two mutant homozygotes? Explain briefly.
INSTRUCTIONS
Go to the OMIM database on the NCI portal. Search for PAH, select the first record on the list The following page will appear: Read the initial information Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of the enzyme PAH (Phenylalanine Hydroxylase). Lack of PAH enzyme activity results in elevated level of phenylalanine. On the other hand, mutations in the PAH gene can also result in a milder disease called hyperphenylalaninemia (HPA) characterized by an elevated level of phenylalanine without the cognitive impairment associated with PKU. QUESTIONS
Question 1: Consider two actual DNA mutations found as 2 PAH mutant alleles. a. Mutation # 0017 changes codon 414 from a tyrosine to a cysteine (TYR414CYS). A homozygous genotype leads to HPA. Indicate the type of mutation for 0017 at the DNA level. Identify the class of mutation at the protein level. Based on the disease phenotype, would you expect the mutated protein to be partially functional or non-functional? (I think it is functional..? http://www.omim.org/entry/612349) Explain your reasoning briefly b. . Mutation #0018 is a mutation that changes the splice site of intron 4 (IVS4). Explain the consequence of mutation 0018 at the level of transcription of the gene, splicing and protein synthesis. Homozygous 0018 leads to PKU phenotype Question 3: Assume an individual heterozygote for 0017/0018. ?Which special term is used to describe a heterozygote with two different mutant alleles - Compound heterozygote Where along the dominance-recessivity scale would the phenotype of this individual falls in relation to the phenotype of the two mutant homozygotes? Explain briefly.
