Chapter 12, Problem 1CS

CASE STUDY | A drug that sometimes works

A 30-year-old woman with β-thalassemia, a recessively inherited genetic disorder caused by absence of the hemoglobin β chain, had been treated with blood transfusions since the age of 7. However, in spite of the transfusions, her health was declining. As an alternative treatment, her physician administered 5-azacytidine to induce transcription of the fetal β hemoglobin chain to replace her missing β chain. This drug activates gene transcription by removing methyl groups from DNA. Addition of methyl groups silences genes. However, the physician expressed concern that approximately 40 percent of all human genes are normally silenced by methylation. Nevertheless, after several weeks of 5-azacytidine treatment, the patient's condition improved dramatically. Although the treatment was successful, use of this drug raises several important questions.

Why was her physician concerned that a high percentage of human genes are transcriptionally silenced by methylation?

Summary Introduction

Case summary:

A 30-year-old woman with β-thalassemia had been treated with a blood transfusion since the age of 7. In spite of transfusions, her health was declining. So, in order to improve the health, her physician gave her 5-azacytidine to induce transcription of fetal β hemoglobin chain to replace the missing β chain.

Characters in the case:

A 30-year-old woman with a recessively inherited genetic disorder called β-thalassemia.

Adequate information:

Her health was declining in spite of transfusions and her physician gave her alternative treatment of 5-azacytidine for the induction of transcription of fetal β hemoglobin. This drug helps in activating transcription of genes by removing methyl groups.

To determine: The concern of the physician about the fact that a high percentage of human genes is transcriptionally silenced by methylation.

Explanation of Solution

Given the information:

Addition of methyl groups silences approximately 40% (percent) of all human genes by methylation.

Beta thalassemia is a recessively inherited genetic disorder. This disorder is characterized by the reduction in the production of beta chains of the hemoglobin molecule. The person suffering from this disorder is not able to produce the hemoglobin in sufficient amount and it leads to the anemic condition of the patient. Hemoglobin is an iron-containing protein of erythrocytes, which helps in carrying the oxygen throughout the whole body. Deficiency in this protein leads to an anemic condition of the body.

In this case, the woman is having β-thalassemia and is cured by regular transfusion of blood. But, her physician provides her with an alternative treatment of 5-azacytidine for induction of fetal β globin genes. This drug is very effective in increasing the synthesis of gamma-globin genes. The production of globin genes by reactivation of fetal globin genes rapidly occurs in bone marrow cells of the patient.

Methylation of DNA (deoxyribonucleic acid) is very necessary for controlling the expression of genes. Methylation of DNA takes place at the globin synthesis site during the treatment. DNA methylation helps in controlling or repressing the gene transcription and helps in the normal development of the body. So, this drug acts by removing the methyl groups from the DNA and thereby activating the transcription of genes responsible for producing fetal β globin genes. So, if a high number of human genes is transcriptionally silenced by methylation, there would be the possibility of production of lethal and mutagenic effects or lesions.

Conclusion

Thus, it can be concluded that the treatment of thalassemia by providing 5-azacytidine is a good option. It enhances the beta globin chains production by silencing the methylation of certain genes.