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


METHODS
Two 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.


RESULTS
Heterozygosity 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.


CONCLUSIONS
This study represents an intragenic polymorphism, IVSII-74, a reliable position with high heterozygosity rates in Iranian population for PND analysis.


TRIAL REGISTRATION
Retrospectively registered.
['Hashemi-Soteh|Mohammad Bagher|MB|', 'Mousavi|Seyed Saeed|SS|', 'Tafazoli|Alireza|A|']
D015415:Biomarkers D003430:Cross-Sectional Studies D005260:Female D005787:Gene Frequency D008040:Genetic Linkage D006239:Haplotypes D006801:Humans D007492:Iran D008297:Male D011110:Polymorphism, Genetic D011247:Pregnancy D011296:Prenatal Diagnosis D055544:beta-Globins D017086:beta-Thalassemia
Haplotypes Beta-globin gene Beta-thalassemia Prenatal diagnosis Mazandaran