Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran

Journal of Biomedical Science

Research

Alireza Tafazoli¹  Mohammad Bagher Hashemi-Soteh²  Seyed Saeed Mousavi³ 

[1] Department of Biochemistry, Biophysics and Genetics, School of Medicine, Mazandaran University of Medical Sciences, P.O. Box. 481751665, Farahabad Road, Sari, Mazandaran, Iran;Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;Immunogenetic Research Center, Molecular and Cell biology Research Center, Medical Faculty, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran;Department of Biochemistry, Biophysics and Genetics, School of Medicine, Mazandaran University of Medical Sciences, P.O. Box. 481751665, Farahabad Road, Sari, Mazandaran, Iran;Novin Genetics diagnostic laboratory, Farah Abad 4, Farah Abad Boulevard, Sari, Mazandaran, Iran;

关键词: Beta-thalassemia;    Beta-globin gene;    Haplotypes;    Prenatal diagnosis;    Mazandaran;   

DOI  :  10.1186/s12929-017-0396-y

 received in 2017-07-25, accepted in 2017-11-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBeta-thalassemia is common in the Mediterranean area as well as the Middle East and India. Official report in Iran revealed the average prevalence rate of carriers about 4%. More than 20 restriction fragment length polymorphisms (RFLPs) are known in the beta-globin gene cluster and used in the prenatal diagnosis (PND) services. Some of these locations may have low allele frequency and are not informative in the prenatal diagnosis. The current study aims to find new haplotypes and polymorphisms with high allele frequency in the local population.MethodsTwo thousand three hundred fifty samples (1,321 male and 1,029 female) from the northern Iran, whom suspected to be the carriers either for alpha or beta thalassemia and referred to the local diagnostic laboratory as a routine services were investigated during five years, (2010–2015). The beta-globin gene was sequenced for all samples.ResultsHeterozygosity for five SNPs in the beta-globin gene was calculated separately. 383 individuals (16.29%) showed no sign of nucleotide change in the beta-globin gene sequence. In total, codon2 (C/T) 31.72%, IVSII-16 (C/G) 31.72%, IVSII-74 (G/T) 54.71%, IVSII-81 (C/T) 19.47%, and IVSII-666 (T/C) 31.72% were seen respectively. Although all five polymorphisms showed reasonably high heterozygosity, IVSII-74 (G/T) [GG wild type (36.5%), G/T (54.71%) and TT (8.8%)] revealed the highest heterozygosity rate. Four combinations of these five SNPs were defined as new haplotypes named M1 to M4. ARMS-PCR also were designed and applied to detect IVSII-74 (G/T) nucleotide position.ConclusionsThis study represents an intragenic polymorphism, IVSII-74, a reliable position with high heterozygosity rates in Iranian population for PND analysis.Trial registrationRetrospectively registered.

【 授权许可】

CC BY   
© The Author(s). 2017