Mutations Phenylketonuria PKU an inability to break down the

Mutations

Phenylketonuria (PKU), an inability to break down the amino acid phenylalanine, can be caused by a number of different mutations in the phenylalanine hydroxylase gene. Different mutations affectthe activity of the enzyme to different extents, leading to more or less severe forms of PKU. Below are some actual alleles of the gene that codes for the phenylalanine hydroxylase enzyme The sequences shown are the coding sequence only of different regions of the same gene. Sequences A, B and D show the downstream sequences. Only sequence C shows the nucleotides immediately following the required start codon, ATG. The promoter would be just to the left of this ATG sequence. Find and mark where the nucleotide change has occurred between the normal and mutant DNA sequence. Use the codon table to determine how the mutation in the DNA will affect the amino acid sequence. In some cases, you may need to look at more than just the single change because it may affect other codons downstream A. Allele A, identified in Swiss patients. Kind of Effect on Effect on norma 5 ATG...GGT GGC CTG GCC TTC CGA GTC TTT...3\' transcription translation mutation Allele A 5\'ATG...GGT GGC CTG GCC TTC CAA GTC TTT...3\'

Solution

Answer A)kind of mutation -Transition base substitution mutation because(G is substituted by A)

Effect on transcription - mRNA formed contain UUG at place of UCG and rest all will be the same as old

Transcript of new sequence will be

5 \'AAA GAC UUG GAA GGC CAG GCC ACC CAU 3\'

Effect on translation

Ser Amino acid at the point of mutation exchange with leu in new polypeptide chain.because only one amino acid change in polypeptide chain mutation effect will not be sever.

B)kind of mutation -Transversion base substitution mutation because purineA substituted by pyrimidine T

Effect on transcription - transcript of new sequence contains

AAC at the place of UAC and the new transcript will be

5\'AGC AAA GUU CCU AAC UU CUC CUU...3\'

Effect on translation - only one amino acid tyrosine exchange with asparagine in new polypeptide chain because UAC codes for tyrosine and AAC codes for asparagine. No big effect will be on protein formation because the mutation is on down stream.

C) mutation type -Transition base substitution mutation because A purine substituted with G purine

Effect on transcription - the new transcript formed will have CAC codon at the place of CAU at 3\' end

Effect on translation - there will be no change in new polypeptide chain because both codon code for same amino acid i.e histidine.

D)kind of mutation - Deletion mutation because T is deleted from the chain

Effect on transcription - transcript after mutation point will be Change the new transcript will be

5\' UGU CAU CAU UCU UUA CCU CAA UAA CAU...3\'

Effect on translation - amino acid sequence change from the point of mutation and even translation stop just before 1 Amino acid near 3\' end because of the presence of stop codon UAA .and the protein form will be non functional.