Molecular Study of Deletional and Nondeletional Mutations on the α-Globin Locus in the Azeri Population of Northwestern Iran.
The aim of this study was to determine the molecular spectrum and frequency of deletional and nondeletional α-thalassemia (α-thal) mutations and the genotype-phenotype correlation in common mutations in the Azeri population of Northwestern Iran. A total of 1256 potential carriers with microcytic and hypochromic anemia and normal Hb A2levels (<3.5%) and without iron deficiency anemia plus three fetuses were identified. Multiplex gap-polymerase chain reaction (gap-PCR) and sequencing for α-thal mutations were carried out. In 606 individuals, the α-globin gene was normal, but in 650 persons (51.6%) and three fetuses, 10 different mutations were detected. The most frequent deletional genotypes were as follows: αα/-α3.7(61.7%), -α3.7/-α3.7(11.9%), αα/-α4.2(4.6%), αα/- -MED(4.3%) and αα/-(α)20.5(3.8%). The most frequent nondeletional genotypes were αα/αIVS-I (-5 nt)α (HBA2: c.95+2_95+6delTGAGG) and αα/αPoly A2α [polyadenylation signal (polyA2) (AATAAA>AATGAA); HBA2: c.*96G>A] with frequencies of 1.08% and 0.92%, respectively. Meanwhile, 7.71% of individuals with a proven β-thalassemia (β-thal) mutation were found to also carry an α-thal mutation. Persons having two functional α-globin genes showed lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values compared to those with one mutated α-globin gene, provided that they had normal β-globin genes. Overall, the incidence of α-thal was 2.7% in the Azeri population in Northwestern Iran. Our results showed that the variability of α-thal mutations are high in the Azeri population and that α-thal mutations are highly heterogeneous in both deletional and nondeletional genotype aspects.
a Haematology and Oncology Research Centre , Tabriz University of Medical Sciences , Tabriz , Iran.|b Medical Genetic Department, Medical Faculty , Tabriz University of Medical Sciences , Tabriz , Iran.|c Ebne Sina Medical Genetics Laboratory, Specialized and Sub-specialized Outpatient Clinics , Tabriz University of Medical Sciences , Tabriz , Iran.
Sima M
SM
Derakhshan
a Haematology and Oncology Research Centre , Tabriz University of Medical Sciences , Tabriz , Iran.|b Medical Genetic Department, Medical Faculty , Tabriz University of Medical Sciences , Tabriz , Iran.|c Ebne Sina Medical Genetics Laboratory, Specialized and Sub-specialized Outpatient Clinics , Tabriz University of Medical Sciences , Tabriz , Iran.
Mahmoud S
MS
Khaniani
b Medical Genetic Department, Medical Faculty , Tabriz University of Medical Sciences , Tabriz , Iran.
Fateme
F
Afkhami
a Haematology and Oncology Research Centre , Tabriz University of Medical Sciences , Tabriz , Iran.
Abbasali H
AH
PourFeizi
D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D009154:Mutation; D011247:Pregnancy; D017384:Sequence Deletion / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000453:epidemiology / Q000235:genetics*
D055542:alpha-Globins
Azeri population; Iran; multiplex gap-polymerase chain reaction (gap-PCR); α-Thalassemia (α-thal)