A 14-year-old boy with chronic anemia is being evaluated after experiencing several episodes of chest, back, and extremity pain. Peripheral blood smear shows sickle-shaped red cells. Genetic testing reveals that the patient is homozygous for a point mutation in the beta-globin gene, resulting in a glutamic acid to valine substitution at position 6. Sequencing of the beta-globin gene would most likely reveal which of the following changes? (The genetic code is shown in the figure below.)

Question

A 14-year-old boy with chronic anemia is being evaluated after experiencing several episodes of chest, back, and extremity pain.  Peripheral blood smear shows sickle-shaped red cells.  Genetic testing reveals that the patient is homozygous for a point mutation in the beta-globin gene, resulting in a glutamic acid to valine substitution at position 6.  Sequencing of the beta-globin gene would most likely reveal which of the following changes? (The genetic code is shown in the figure below.)

Quizplus · Accepted Answer

11ec160b_377d_42b3_9249_8fac1df3463b_MD0001_00 This patient has sickle cell disease (SCD), an autosomal recessive hematologic disorder resulting in hemoglobin molecules that polymerize during times of hypoxic stress. SCD results from a DNA point mutation in the coding region of the hemoglobin beta-globin chain. This single nucleotide substitution is a missense mutation that causes a glutamic acid to valine substitution at position 6 during protein translation. The genetic code figure shows that 2 distinct nucleotide combinations code for glutamic acid, GAG and GAA. In addition, only 2 possible single nucleotide substitutions could occur in DNA that result in glutamic acid being replaced by valine, GAA → GTA and GAG → GTG. (Choices A, B, and F) Examples of missense mutations include glutamine (CAA) substitution by valine (GTT), histidine (CAT) substitution by leucine (CTT), and valine (GTA) substitution by glutamic acid (GAA). However, they are unrelated to SCD. (Choice C) This substitution results in a silent mutation as both TTA and CTA code for leucine. (Choice D) A codon change from GAA to GUA also results in glutamic acid being replaced by valine. However, the pyrimidine base uracil occurs only in RNA (not DNA), so it would only be present in the mRNA transcript that codes for the beta-globin protein and not in the beta-globin gene itself. Educational objective: Sickle cell disease is the result of a missense mutation that causes valine to replace glutamic acid at position 6 in the hemoglobin beta-globin chain. RNA contains the pyrimidine base uracil, whereas DNA contains the base thymidine. __________ References: Sickle cell pathophysiology (http://www.ncbi.nlm.nih.gov/pubmed/25282490)

A 14-Year-Old Boy with Chronic Anemia Is Being Evaluated After