Molecular and Haematological Characteristics of alpha-Thalassemia Deletions in Yogyakarta Special Region,Indonesia

Background:alpha-Thalassemia is caused primarily by deletions of one to two alpha-globin genes and is characterized by absent or deficient production of alpha-globin protein. The South-East Asia (SEA) deletion, 3.7-kb and 4.2-kb deletions are the most common causes. The present study aimed to observe the molecular characteristics of this common alpha-Thalassemia deletions and analyse its haematological parameter.Methods:Blood samples from 173 healthy volunteers from thalassemia carrier screening in Yogyakarta Special Region were used. Haematological parameters were analysed and used to predict the carrier subjects. Genotype of suspected carriers was determined using multiplex gap-polymerase chain reaction and its haematological parameters were compared. The boundary site of each deletion was determined by analysing the DNA sequences.Results:Seventeen (9.8%) of the volunteers were confirmed to have alpha-Thalassemia trait. Of these, four genotypes were identified namely –α^3.7/αα (58.8%), –α^4.2/αα (5.9%), –α^3.7/–α^4.2 (5.9%) and – –^SEA/αα (29.4%). The 5′ and 3′ breakpoints of SEA deletion were located at nt165396 and nt184700 of chromosome 16, respectively. The breakpoint regions of 3.7-kb deletion were 176-bp long, whereas for 4.2-kb deletion were 321-bp long. The haematological comparison between normal and those with alpha-Thalassemia trait genotype indicated a significant difference in mean corpuscular volume (MCV) (p< 0.001) and mean corpuscular haemoglobin (MCH) (p< 0.001). As for identifying the number of defective genes, MCH parameter was more reliable (p= 0.003).Conclusion:The resultant molecular and haematological features provide insight and direction for future thalassemia screening program in the region.Key Words: Allelic Imbalance, Alpha-Thalassemia, Indonesia, Multiplex Polymerase Chain Reaction, Sequence Deletion