Haplotype Analysis in Carriers of β-Globin Gene Mutation Facil-itates Genetic Counseling in β-Thalassemia: A Cross-Sectional Study in Kerman Province, Iran
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Abstract
Background: β-thalassemia is characterized by reduced synthesis of the hemoglobin beta chain that results in microcytic hypochromic anemia and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. β-thalassemias are caused by mutations in the β-globin gene, inherited in an autosomal recessive manner. Determining molecular defects in couples carrying β-thalassemia is a prerequisite for prenatal diagnosis of the disease. In this regards, database of β-globin gene haplotypes facilitates mutation detection of the gene and helps genetic counselors to reach the goals of β-thalassemia prevention program.
Methods: In this cross-sectional study, 255 couples attended genetic counseling between December 2017 and January 2019 in Afzalipour Hospital, Kerman University of Medical Scinces, Kerman, Iran as suspicious of β-thalassemia carriers. Furthermore, they were investigated using amplification refractory mutations system-polymerase chain reaction and restriction fragment length polymorphism methods for mutation screening and haplotype analysis of polymorphic sites in β-globin gene cluster, respectively.
Results: We identified 20 different types of β-globin gene mutation in 449 β-thalassemia carriers. Analysis of the pattern of Hind III/Gγ, Hinf I/5′β, Hinc II/3′Ψβ, Rsa I/5′β, AvaII/β and Hind III/Aγ polymorphic sites in 257 alleles of informative families revealed 17 different haplotypes. Haplotype 1 (77.24%) showed strong linkage with the most common mutation IVSI-5 while haplotype 5 (66.67%) was associated with the second frequent mutation IVSII-1.
Conclusion: To our knowledge, these β-globin haplotypes are reported for the first time which are different with those found in other parts of Iran. The current haplotypes pattern data makes the counseling of β-thalassemia carriers more straightforward and the process of mutation screening faster and more accurate.
Saleh-Gohari N, Bazrafshani MR (2010). Distribution of β-Globin Gene Mutations in Thalassemia Minor Population of Kerman Province, Iran. Iranian J Publ Health, 39: 69-76.
Giardine B, van Baal S, Kaimakis P, Riemer C, Miller W, Samara M, Kollia P, et al (2007). HbVar database of human haemoglobin variants and thalassemia mutations. Hum Mutat, 28:206.
Rahimi Z (2013). Genetic Epidemiology, Hematological and Clinical Features of Hemoglobinopathies in Iran. Biomed Res Int, 803487.
Najmabadi H, Karimi-Nejad R, Sahebjam S, Pourfarzad F, Teimourian S, Sahebjam F, et al (2001). The beta-thalassemia mutation spectrum in the Iranian population. Hemoglobin, 25: 285-96.
Samavat A, Modell B (2004). Iranian national thalassemia screening program. BMJ, 13:1134–7.
Xiong F, Lou JW, Wei XF, Sun MN, Huang JW, Shang X, et al (2012). Analysis of hematological characteristics on the 79 co-inheritance of α-thalassemia and β-thalassemia carriers in Guangxi. Zhonghua Xue Ye Xue Za Zhi, 33: 856-60.
Fereshteh M, Azita A, Mohammad SF, Sirous Z (2015). A Large Cohort Study of Genotype and Phenotype Correlations of Beta-Thalassemia in Iranian Population. Int J Hematol Oncol Stem Cell Res, 9:198–202.
Saleh-Gohari N, Khademi Bami M, Nikbakht R, Karimi-Maleh H (2015). Effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers. J Clin Pathol, 0:1–5.
Forget BG, Pearson HA (1995), Hemoglobin synthesis and the thalassemias, in: R.I. Handin, S.E. Lux, T.P. Stossel (Eds.), Blood: Principles and Practice of Hematology, J.B. Lippincott Company, Philadelphia , 1525–1590.
Saleh-Gohari N, Mashizi AK (2009). A family with the 619 bp deletion on the beta-globin gene found in Kerman Province, Iran. Hemoglobin, 33:515-8.
Lee YJ1, Park SS, Kim JY, Cho HI (2002). RFLP haplotypes of beta-globin gene complex of beta-thalassemic chromosomes in Koreans. J Korean Med Sci, 17:475-8.
Kaplan F, Kokotsis G, DeBraekeleer M, Morgan K, Scriver CR (1990). Beta-thalassemia genes in French-Canadians: haplotype and mutation analysis of Portneuf chromosomes. Am J Hum Genet, 46:126-32.
Kazazian HH Jr, Orkin SH, Antonarakis SE, Sexton JP, Boehm CD, Goff SC, et al (1984). Molecular characterization of seven beta-thalassemia mutations in Asian Indians. EMBO J, 3:593-6.
Falchi A, Giovannoni L, Vacca L, Latini V, Vona G, Varesi L (2005). beta-Globin Gene Cluster Haplotypes Associated With beta-Thalassemia on Corsica Island. Am J Hematol, 78:27-32.
Rahimi Z, Muniz A, Akramipour R, Tofieghzadeh F, Mozafari H, Vaisi-Raygani A, et al (2009). Haplotype analysis of beta thalassemia patients in Western Iran. Blood Cells Mol Dis, 42:140-3.
Akhavan-Niaki H1, Derakhshandeh-Peykar P, Banihashemi A, Mostafazadeh A, Asghari B, Ahmadifard MR, et al (2011). A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population. Blood Cells Mol Dis, 47:29-32.
Rahimi z, Merat A, Akhzari M, haghshenass M, ronaled LN, Nathalie G, et al (2005). β-globin gene cluster haplotypes in Iranian patients with β-thalassemia. IJHOBMT, 2:30-34.
Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res,16:1215-16.
Newton CR, Graham A, Heptinstall LE, Powell SJ, Summeres C, Kalsheker N, et al (1989). Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res,17: 2503-16.
Saleh-Gohari N, Khosravi-Mashizi A (2010). Spectrum of α-globin gene mutations in the Kerman province of Iran. Hemoglobin, 34:451–460.
Yavarian M, Harteveled CL, Batelaan D, Bernini LF, Giordano PC (2001). Molecular spectrum of beta-thalassemia in the Iranian Province of Hormozgan. Hemoglobin, 25: 35-43.
Miri Moghadam E, Narooie Nejad M, Eshgi P, Zeinali S, Savad koohi F (2005). Molecular basis and prenatal diagnosis of -Thalassemia in southeast of Iran. Journal of Mazanderan University of Medical Sciences,48: 105-11.
Saleh-gohari N, Mohammadi-Anaie M (2012). Co-inheritance of sickle cell trait and thalassemia mutations in south central Iran. Iranian J Publ Health, 41:81-86.
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| Issue | Vol 49 No 4 (2020) | |
| Section | Original Article(s) | |
| Keywords | ||
| Beta-thalassemia; Beta-globin gene; Haplotype Iran | ||
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