Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran
,
Abstract
Background: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran.
Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in the β-globin gene, the frequency of RFLP haplotypes, and LD between markers at β-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of β-globin gene and BamHI 3' to the β-globin gene. All statistical analyses were performed using Power Marker software and SISA server.
Results: Fifty percent of beta-thalassemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%).
Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess similar haplotype background for common mutations.The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers.
Rahimi Z, Vaisi Raygani A, Merat A, et al. Thalassemic mutations in Southern Iran. Ir. J. Med. Sci. 2006; 31(2):70-73.
Derakhshandeh-Peykar P, Hourfar H, Heidari M, et al. The Spectrum of β -thalassemia Mutations in Isfahan Province of Iran. IJPH; 2008; 37(2):106-111.
Senol SP, Tiftik EN, Unal S, et al. Quality of life, clinical effectiveness, and satisfaction in patients with beta thalassemia major and sickle cell anemia receiving deferasirox chelation therapy. J Basic Clin Pharm. 2016; 7(2):49-59.
Raza SH, Waseem Shoaib M, Mubeen H. Genetic Markers: Importance, uses and applications. IJSRP. 2016; 6(3):221-23.
Gupta A, Sarwai S, Pathak N, et al. Beta-globin gene mutations in India and their linkage to β-haplotypes. Int J Hum Genet. 2008; 8:237-241.
Gattepaille LM, Jakobsson M. Combining markers into haplotypes can improve population structure inference. Genetics. 2012; 190(1):159-74.
Falchi A, Giovannoni L, Vacca L, et al. beta-globin gene cluster haplotypes associated with beta-thalassemia on Corsica island. Am J Hematol. 2005; 78(1):27-32.
Lee YJ, Park SS, Kim JY, et al. RFLP haplotypes of beta-globin gene complex of beta-thalassemic chromosomes in Koreans. J Korean Med Sci. 2002; 17(4):475-478.
Ozturk O, Atalay A, Koseler A, et al. Beta globin gene cluster haplotypes of abnormal hemoglobins observed in Turkey. Turk J Hematol. 2007; 24:146-54.
Wood ET, Stover DA, Slatkin M, et al. The β-globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria. AJHG. 2005; 77(4):637-642.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215.
Rahimi Z, Muniz A, Akramipour R, et al. Haplotype analysis of beta thalassemia patients in Western Iran. Blood Cells, Molecules, and Diseases. 2009; 42(2):140-143.
Lee YJ, Park SS, Kim JY, et al. RFLP Haplotypes of-Globin Gene Complex of-Thalassemic Chromosomes in Koreans. J Korean Med Sci. 2002; 17(4):475-8.
Najmabadi H, Karimi-Nejad R, Sahebjam S, et al. The beta-thalassemia mutation spectrum in the Iranian population, Hemoglobin. 2001; 25(3):285-96.
Orkin SH, Kazazian HH Jr, Antonarakis SE, et al. Linkage of beta-thalassemia mutations and beta-globin gene. Nature. 1982; 296(5858):627-31.
Antonarakis SE, Boehm CD, Giardina PJ, et al. Nonrandom association of polymorphic restriction sites in the β-globin gene cluster. Proc Natl Acad Sci U S A. 1982; 79(1):137-141.
Rahimi Z, Merat A, Akhzari M, et al. β-Globin Gene Cluster Haplotypes in Iranian Patients with β-Thalassemia. IJHOBMT. 2005; 2(6):30-34.
Hashemi-Soteh MB, Mousavi SS, Tafazoli A. Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran. J Biomed Sci. 2017; 24(1):92.
Falchi A, Giovannoni L, Vacca L, et al. beta-globin gene cluster haplotypes associated with beta-thalassemia on Corsica island. Am J Hematol. 2005; 78(1):27-32.
Zahed L. The spectrum of β-thalassemia mutations in the Arab populations. J Biomed Biotech 2001; 1:129-32.
Martins JTN, Bordin S, De Albuquerque DM, et al. Dnase I hypersensitive site 3' to the beta globin gene cluster containing two TAA insertions and a G>A polymorphism is predominantly associated with the beta+ thalassemia IVS-I-6 (T>C) mutation. Hemoglobin. 2005; 29:85-9.
Kukreti R, Dash D, E VK, et al. Spectrum of-Thalassemia Mutations and Their Association With Allelic Sequence polymorphisms at the beta-globin gene cluster in an Eastern Indian population. Am J Hematol. 2002; 70(4):269-77.
Zahed L, Qatanani M, Nabulsi M, et al. β-thalassemia mutations and haplotype analysis in Lebanon. Hemoglobin. 2000; 24(4):269–276.
Zahed L, Demont J, Bouhass R, et al. Origin and history of the IVS-I-110 and codon 39 beta thalassemia mutations in the Lebanese population. Hum Biol. 2002; 74:837-47.
Bahadır A, Oztürk O, Atalay A, et al. Beta globin gene cluster haplotypes of the beta thalassemia mutations observed in the Denizli province of Turkey. Turk J Hematology. 2009;26(3):129-137.
Rahimi Z, Karimi M, Haghshenas M, et al. Beta globin gene cluster haplotype in cycle cell patient from Southwest Iran. American Journal of Hematology. 2003; 74:156-60.
| Files | ||
| Issue | Vol 13, No 2 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v13i2.690 | |
| Keywords | ||
| Haplotype; Beta-thalassemia; c.315 1G>A; c.92 5G>C; c.93-21G>A | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
