Rey Williams was a small but healthy baby girl. The family pediatrician wasn’t w

Question

Rey Williams was a small but healthy baby girl. The family pediatrician wasn’t worried as both her parents were petite. However, at about the age of 13 months Rey stopped running around, tired easily, was pale and lost her appetite- symptoms that could not be explained by a recent flu bug going around as it lasted for months. Concerned the family pediatrician Dr. Wright decided to draw Rey’s blood to check for inherited blood-disorders.

At the next office visit, Dr. Wright sat Rey’s mother down and gently gave her the bad news. As he suspected it was determined that Rey had Thalassemia- an inherited disorder resulting from a defective for ?-globin protein- and thus defective Hemoglobin.

?-thalassemia patients are treated with frequent transfusions requiring many hospital visits, but this is not a cure. Individuals with severe forms of ?-thalassemia often die in mid-teens. Dr.Wright suggested to Rey’s parents that she may be a candidate for experimental gene therapy but first they needed a quick test to see if Rey had the kind of defect that would qualify for gene therapy. They isolated mature mRNA from Rey’s RBCs and from a person without Thalassemia(N). They then mixed the mRNA with single stranded genomic DNA sequences of the Beta Globin gene to allow for hybridization and observed it by electron microscopy. Double-stranded regions(hybridized) are represented by thick lines, and single-stranded regions (un-hybridized) are represented by thin lines.

Q2. Based on the hybridization experiments what can the pediatrician deduce about the

molecular nature of the defect in Rey’s globin gene? (2pts)

[Note: In writing your answer also make a prediction about what kind(s) of mutations could

result in that change seen and what that does to the B-globin protein]

Sequencing a region of the Beta-globin gene covering exon 2- intron 2- exon 3 revealed

the following mutations within intron 2 when compared to normal beta globin gene

(mutations underlined). The corresponding mRNA therefore would look like below.

Explanation / Answer

Ray globin gene has more single stranded region in hybridization experiment than the normal beta globin mRNA. Ray globin gene undergoes point mutation which lead to failure of globin gene. This lead to change in mRNA codon and corresponding amino acid so that beta globin gene become nonfunctional.

According to beta globin gene sequence point mutation change the glu acid codon to gln and val replace by glycine. Therefore, this misense mutation make b - globin protein nonfunctional and result in thalassemia.

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