BMS315 - HBB Gene: Molecular Genetics of Beta Thalassemia Disease

This report provides a detailed overview of the HBB gene and its association with beta thalassemia, a blood disorder characterized by reduced hemoglobin production. It explores the genetic mutations within the HBB gene, which encodes for beta-globin, a crucial component of hemoglobin responsible for oxygen transport. The report discusses the gene's structure, chromosomal location, and expression patterns, as well as the various mutations that lead to the disease. It examines the genomics, transcriptomics, proteomics, and phenomics aspects of beta thalassemia, including the impact of mutations on protein structure and function. The report also reviews recent research, including studies on gene therapy approaches like CRISPR/Cas9, aimed at correcting HBB gene mutations. It highlights the complexities of the disease, current limitations in research, and the ongoing search for effective treatments, providing a comprehensive understanding of the disease and potential therapeutic strategies.

Running head: HBB GENE: BETA THALASSEMIA
HBB GENE: BETA THALASSEMIA
Name of Student:
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Author’s Note:

1HBB GENE: BETA THALASSEMIA
Introduction
Beta thalassemia is the disease where the production of the haemoglobin gets reduced,
thus leading to a decrease in the flow of oxygen in the body. It is the autosomal disorder of the
blood which results in severe microcytic hypochromic anaemia, low level of haemoglobin A and
abnormal blood smear. The disorder is caused by a genetic mutation in the HBB gene, which
plays significant role in sending the signal for the production of a protein known as beta-globin
(Vucak et al., 2018). The protein beta-globin is a subunit of haemoglobin which has the function
of carrying oxygen in the blood. Thus, the mutation in the HBB gene, prevent the transcription
and translation process of the gene and protein is not produced in the body. Absence of beta-
globin leads to a reduced amount of functional haemoglobin and cause Beta-thalassemia.
In the research of the HBB gene has led to a better understanding of the disease process.
It is observed in the study of Thanh et al. (2018) that HBB gene helps to determine and regulate
the structure of two types of the polypeptide chain of haemoglobin Hb A. Identification of the
pathogenic variant in the molecular genetic testing of HBB gene has been useful in the diagnosis
of the disease. The hematologic finding of microcytic hypochromic anaemia has stated that the
mutation in the gene sequence of the HBB has cause single protein change which is located in
chromosome number 11. In the research of Traivaree et al. (2018), it is revealed that due to the
interaction of Hb E and Hb Yala and frameshift mutation of the beta-globin gene result in Beta-
Thalassemia. The author has done DNA analysis which suggested that due to mutation truncated
B globin chain is terminated at codon 60, leading to null thalassemia. Thus, this finding can be
helpful in the diagnosis of the disorder. However, it also requires to investigate the sequence of
the HBB gene to evaluate the prognosis of the disease.

2HBB GENE: BETA THALASSEMIA
In the research of Ekwattanakit, Riolueang and Viprakasit (2018) analysis of HBB has
also revealed that it has a highly homologous gene sequence and pseudogene known as HBBP1.
It has given new insight into the prognosis of the disease. Due to the change in single gene base
of the HBB disrupt the protein which makes up Hb A. The X-ray crystallography has suggested
the distorted structure of the beta-globin protein, which has caused low production of the
haemoglobin. In the study of Mahdieh and Rabbani (2016), there has been researching on the
variation of HBB gene by evaluating 1000 genomes database with the objective to describe the
frequency of mutation of a diverse population with reference to HG19 genome. The author has
observed that there is a high frequency of mutated gene; however, 90% of the case does not lead
to beta thalassemia because they are located in the non-coding region of HBB gene. Author has
made a concluding remark that out of 10000 people in world, 14 peoples are at the risk of
developing beta thalassemia in the next generation.
Considering the high prevalence of the disease, research has been conducted to find the
effective mean of treatment. This has also given new insight into the treatment. The researched
has given the theory that by improving the sequence of HBB gene, Beta thalassemia can be
treated or cured. However, research has failed to correct the gene sequence of HBB (Saetung et
al., 2017). Hence, this requires extensive research to search for exact mean of treatment of beta-
thalassemia.
Concerning to the diagnosis, prognosis and treatment of the beta-thalassemia, Cai et al.
(2018) have conducted a universal approach to correct the gene mutation of HBB gene of human
stem cell for gene therapy. The author has explored the CRISPR/Cas9 approach to perform HBB
gene editing by the use of humanized SpCas9 protein. While other researchers are working in
developing genome editing in the postnatal CD34+, which is known to depress the expression

3HBB GENE: BETA THALASSEMIA
level of HBG in RBC (Bai et al., 2017), it has the competence to substitute the missed HBB in
the region of B-thal and help to produce HBB protein and increase the level of haemoglobin in
blood. Both recent findings are still in further investigation to determine the effectiveness at the
commercial level.
Lastly, from the above discussion, it can be concluded that numerous studies have been
conducted in the HBB gene and its mutation leading to beta-thalassemia. However, there have
been the various limitation in the current understanding of the HBB gene. No relevant study has
been conducted to find the mechanism of action that leads to the mutation of the HBB gene.
Therefore, research must be explored to evaluate the classification and detail description of the
disease.

4HBB GENE: BETA THALASSEMIA
Reference
Bai, H., Cai, L., Machairaki, V., Gao, Y., Ye, Z., & Cheng, L. (2017). A Universal Approach to
Correct Various HBB Gene Mutations in Human Stem Cells for Gene Therapy of Beta-
Thalassemia and Sickle Cell Disease.
Cai, L., Bai, H., Mahairaki, V., Gao, Y., He, C., Wen, Y., ... & Ye, Z. (2018). A universal
approach to correct various HBB gene mutations in human stem cells for gene therapy of
beta‐thalassemia and sickle cell disease. Stem cells translational medicine, 7(1), 87-97.
Ekwattanakit, S., Riolueang, S., & Viprakasit, V. (2018). Interaction between Hb E and Hb Yala
(HBB: c. 129delT); a novel frameshift beta globin gene mutation, resulting in
Hemoglobin E/β0 thalassemia. Hematology, 23(2), 117-121.
Kim, S. J., Song, J., Phillips, J. D., Reading, N. S., Min, C., Lautersztain, J., ... & Prchal, J. T.
(2017). A Study of Novel Beta Globin Mutation Associated with Dominant Beta-
Thalassemia, Aberrant Erythroid Maturation and Differentiation Compounded with
Hereditary Pyropoikilocytosis.
Mahdieh, N., & Rabbani, B. (2016). Beta thalassemia in 31,734 cases with HBB gene mutations:
pathogenic and structural analysis of the common mutations; Iran as the crossroads of the
Middle East. Blood reviews, 30(6), 493-508.
Saetung, R., Ongchai, S., Charoenkwan, P., & Sanguansermsri, T. (2017). GENOTYPING OF
BETA THALASSEMIA TRAIT BY HIGH-RESOLUTION DNA MELTING
ANALYSIS. Southeast Asian Journal of Tropical Medicine and Public Health, 48(6),
1338-1339.

5HBB GENE: BETA THALASSEMIA
Thanh, H. L. T., Thanh, H. L. T., Luong, L. H., Tran, T. H., Liu, S. C., Truong, H. N., ... & Tran,
V. K. (2018). Prenatal diagnosis of a case with SEA-HPFH deletion thalassemia with
whole HBB gene deletion. Taiwanese Journal of Obstetrics and Gynecology, 57(3), 435-
441.
Traivaree, C., Monsereenusorn, C., Rujkijyanont, P., Prasertsin, W., & Boonyawat, B. (2018).
Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE
disease in Thai children: predictable clinical spectrum using genotypic analysis. Journal
of blood medicine, 9, 35.
Vucak, J., Turudic, D., Milosevic, D., Bilic, M., Salek, Z., Rincic, M., & Bilic, E. (2018).
Genotype-phenotype Correlation of β-Thalassemia in Croatian Patients: A Specific HBB
Gene Mutations. Journal of pediatric hematology/oncology, 40(2), e77-e82.