Question

Japanese researchers examined mutant alleles of a gene that encodes an enzyme, liver-type arginase, in four patients. The normal protein catalyzes the breakdown of the amino acid arginine. In argininemia, lack of the enzyme causes progressive developmental disabilities, spastic limb movements, seizures and stunted growth.

The mRNA transcript for this gene codes for 322 amino acids, but the entire gene is 11.5 kilobases long, and is located on chromosome 6q. Argininemia affects both sexes and is inherited from carrier parents.

Patient A – homozygous for a G mutated to an A at DNA base 365 in the gene

Patient B – homozygous for a G to C mutation at base 703, which substitutes one amino acid for another.

Patient C – has patient A’s mutation and patient’s B mutation.  

Patient D – has patient’s A mutation in one allele, and the other allele is a deletion of a C at position 842.

The researchers evaluated the phenotype associated with each allele by producing the encoded proteins in E. coli cells. Patient A’s abnormal protein is too short. The other mutations yield proteins of normal length that are unstable or otherwise nonfunctional.

1. The mode of inheritance of argininemia is ___________________________________________

2. Patients _____ and ______ are heterozygous for the argininemia gene.

3. Patients ____ and _____have missense mutations for the argininemia gene.

4. Why is patient A’s liver-type arginase too short?

5. Human liver-type arginase can be produces in E. coli because: A) E. coli have livers B) The genetic code is universal C) The genetic code is triplet D) E. coli also uses arginine

6. The argininemia gene has enough bases beyond those in exons to encode ____________more amino acids.

Answer 1

1. The mode of inheritance of argininemia is Autosomal recessive.
   In the given examples, since Argininemia is inherited from Carrier parents, these parents have the allele that causes Argininemia but don't have the disorder themselves. Therefore, Argininemia is an autosomal recessive condition.

2. Patients C and D are heterozygous for the argininemia gene.
   Since both Patient C and Patient D have different alleles for the Arginase gene and are hence heterozygous for the Argininemia gene.

3. Patients B and C have missense mutations for the argininemia gene.
   Patient A has a nonsense mutation as they produce a truncated protein. Patient D has a frameshift mutation one base is deleted from the sequence. Therefore, Patients B and C have mutations that substitute one Amino acid for another. These mutations are alled missense mutations.

4. Why is patient A’s liver-type arginase too short?
   Patient A's liver-type Arginase is too short because of a nonsense mutation. This is a mutation that changes a codon from a peptide coding codon to a stop codon, halting the synthesis of the peptide chain for the protein. As a result, the peptide chain is shorter than the wild-type protein.

5. Human liver-type arginase can be produced in E. coli because:
   B) The genetic code is universal
   Since the Genetic code is universal, all organisms, regardless of complexity, relatedness use the same codons for the same amino acids. This allows us to express Human genes in E. coli as the resulting protein will have the same Amino acid sequence as does the protein found in human livers.

6. The argininemia gene has enough bases beyond those in exons to encode 3511 more amino acids.
   The Arginase gene is 11.5 kB or 11,500 bp long. This means that the gene can code for 11,500/3 3833 (The exact number is ) amino acids. Since the Arginase amino acid is 322 amino acids long, the gene has sufficient nucleotides beyond the Exons to code for 3511 (3833 - 322) more amino acids.