Question

Part 2. Adult hemoglobin is composed of two alpha subunits and two beta subunits. There are several genes that code for proteins closely related to beta globin. Each of Epsilon, Gamma, and Beta can all pair with Alpha globin to form functional hemoglobin. 1. Epsilon: expressed during early embryogenesis. 2. Gamma: expressed during later fetal development. 3. Beta: expressed after fetal development into adulthood All of the beta-family globin genes are regulated by a set of enhancer elements called the LCR. B-thalassemia is a severe deficiency in B-globin due to mutations in the B-globin gene. This leads to a massive imbalance between a- and B-globin, blood cell defects and severe anemia. 5-Azacytidine is a cytosine precursor analog that leads to production of modified dCTP that cannot be methylated. 1. Predict the chromatin status (open, closed) of E, Y, and B globin genes in early embryonic, fetal and adult cells blood precursor cells. 2. Predict the extent of methylation of E, Y, and B globin genes in early embryonic, fetal and adult cells blood precursor cells. 3. 5-Azacytidine has been used as a treatment for B-thalassemia in a few limited cases. Patients receiving 5-Azacytidine had a significant restoration of functional hemoglobin. Come up with an explanation for how 5- Azacytidine achieves this result. 4. 5-Azacytidine has only been allowed to be used in extremely limited trials on very sick individuals because of concerns about side effects. Why would you have serious concerns about 5-Azacytidine side effects?

Answer 1

1 ans) Human beta-globin locus is a genetic system present on Chromatin in closed. Globin locus has five globin genes such as epsilon, gamma and beta, arranged on the chromosome in specific order based on their expression during emryo, fetal and adult cell stages .

Two events takes place in beta-globin gene expression this events indicates the changing oxygen requirements for baby. During first event embryonic epsilon changes to fetal gamma-globin this takes place occurs after five weeks of gestation, during second event gamma globin changes to beta-globin soon after parturation. Low levels of adult globin represents function of erythroid cells of fetus. Fetal to adult formation occur in the ninth of gestation. Changes in globin genes takes place in adult cells and hematopoitic cell.

2 ans) Methylation of gamma globin gene support fetal to adult globin switch, methylation inactivates gamma globin genes.

3 ans) 5-Azacytidine drug is similar cytidine and it can activate repressed genes leading to increased hemoglobin production. In patients suffering with beta-thalassemia it is necessary to stimulate hemoglobin production by administering 5-azacytidine for nearly five days.

4 ans) Administration of 5-Azacitidine has some of the side affects if its level exceeds normal dose, increased level causes anemia (low red blood cell), low white blood cell counts, and low platelet counts.