IJPRAS, 2012; Volume 1(4)
International Journal of Pharmaceutical Research and Applied Science (IJPRAS) A way to rising your innovation and dreams
ISSN 2319-7013
IDENTIFICATION OF β-THALASSEMIA CARRIERS AND TO STUDY COMMON, PERVALENT MUTATION IN CERTAIN HIGH-RISK COMMUNITIES OF GUJARAT RESEARCH ARTICLE Sankha Bhattacharya Department Of Pharmaceutics, Asst. Professor B.Pharmacy College Rampura, Godhra, Gujarat
Corresponding Author Email:
[email protected]
ABSTRACT:
Thalassemia is the most common genetic disorder all over the world. Around 3% of the world’s population carries genes for β-Thalassemia. The complex mutational spectrum of the β-thalassemia, relevant in the multi ethnic community, requires scanning the β-globin genes rapidly and accurately for all mutations. In this Research we tried to study ARMSPCR And the mutations were successfully characterized. This study aimed to evaluate a rapid molecular carrier screening strategy for β-thalassemia. The study can be expanded to identify β-thalassemia carriers and to prevent the birth of homozygous children. The objective is to study occurrence of common mutations in the population of Gujarat and the most prevalent mutation in certain high-risk communities. Key Words: β-Thalassemia, Oligonucleotide sequence, mutations
Online At www.ijpras.co.in
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IJPRAS, 2012; Volume 1(4)
INTRODUCTION: Genetic disorder is a disease caused by abnormalities in an individual’s genetic material (genome) genes or chromosomes. Both environmental and genetic factors have roles in the development of any disease. Most disorders are quite rare and affect one person in every several thousands or millions. Some types of recessive gene disorder confer an advantage in the heterozygous state in certain environments. The four different types of genetic disorders are Single-gene disorder. Multifactorial or polygenic (complex) disorder. Chromosomal disorder. Mitochondrial disorder. HAEMOGLOBINOPATHIES: The ‘Haemoglobinopathies’ includes a heterogenous group of hereditary haemoglobin (Hb) disorders. A genetic defect that results in abnormal structure of one of the globin chains of the haemoglobin molecule. Mutations in the genes for the haemoglobin protein in humans result in a group of hereditary diseases termed the Haemoglobinopathies. Haemoglobinopathies are most common single gene disorder in man (Sarnaik, 2005). The inherited disorders of haemoglobin (Hb) synthesis includes Haemoglobinopathies and Thalassemia (Ehemery & Rimoin, 1990). The disease due to the quality of Hb i.e qualitative Hb disease called Haemoglobinopathies and quantitative Hb disease called as Thalassemia. Among Haemoglobinopathies, the largest group is Thalassemias which are autosomal recessive disorders characterized by reduced or abolished synthesis of globin chains of Hb molecules, causing severe anaemia in homozygotes. They are one of the most common single gene disorders in the world population and among the first diseases studied by using the techniques of molecular biology (Baig et al., 2005). β-thalassemia is the most prevalent monogenic single gene disorder, inherits in the autosomal recessive, in India. It is caused by more than 200 mutations that reduce or abolish synthesis of β globin chain of haemoglobin (May et al., 2002). Numerous studies undertaken subsequently have shown that the prevalence of β-thalassemia varies
from 1 to 17% in different population groups with an overall frequency of 3–4%. Based on this, it is estimated that there would be 30–40 million carriers and almost 8,000 to 10,000 births each year with severe forms of β-thalassemia. This translates to about 10% of the total thalassemia homozygotes or compound heterozygotes born globally and results in a significant national health burden (Sood et al., 1993). Despite this marked heterogenity, each population at risk usually has its own specific set of mutations (five- ten) that accounts for the large majority of the molecular defects causing β-thalassemia (Cao et al., 1997). In well studied populations, different ethnic groups have been found with different types of molecular defects as the basis for β-thalassemia (Kazazian et al., 1984; Wong et al., 1986). Programs based on carrier screening, genetic counseling & prenatal diagnosis are very effective in preventing an autosomal recessive disease such as β-thalassemia, at the population level (Cao et al., 1991). The extent and magnitude of the problem of thalassemia in India is alarming. The affected children become a great source of socioeconomic burden on their families. Life expectancy & quality of life are low for βthalassemia patients. Genetic counseling & prenatal diagnosis can play an important role in reducing the incidence of this disease. Prenatal diagnosis depends on the sound knowledge of the local mutations causing thalassemia ( Kazazian et al., 1990). HUMAN HAEMOGLOBIN: Hb is contained within circulating RBCs. Each RBC contains approximately 300 million molecules of Hb, weighing about 30pg/cell. Hb is tetramer with molecular weight of 64,500, consisting of 2-α and 2 non-α globin peptide chains, each binds covalently with haem group.
A. structure of human haemoglobin. Online At www.ijpras.co.in
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IJPRAS, 2012; Volume 1(4)
B. structure of Heme molecule. Figure: A) structure of human haemoglobin. [The protein α and β subunits are in red and blue, and the iron containing heme group in green.] B) structure of Heme molecule.
DIFFERENT HAEMOGLOBIN TETRAMERS: TABEL 1. different Hb tetramers. (Ehemery & Rimoin, 1990) Hb
synonym
Structure
name
% in
conditions in which increases
adults α2β2
92
A1c
α2 (β-n-glu)2
5
A2
α2δ2
2.5
β-thalassemia, megaloblastic anaemia
α2γ2
