Search

Thalassemia is an inherited blood disorder which is divided into two groups: alpha and beta. HBA1 and HBA2 are the two genes associated with alpha thalassemia. The aim of this study is to investigate abnormal hemoglobin variants of alpha globin gene in healthy abnormal hemoglobin carrying individuals with intact beta globin gene. DNA was extracted from peripheral blood samples of seven healthy carrier individuals who have abnormal hemoglobin variants and 16 control individuals from Turkey. Complete coding and intronic sequences of HBA1 and HBA2 genes were amplified by polymerase chain reaction (PCR) and PCR products of HBA1 and HBA2 were sequenced. We were unable to find any base change in our carrier group in the HBA1 gene. We have observed an A/G polymorphism in the downstream untranslated region (+861 G>A) of the HBA2 gene. Our study showed that 14.29% (1/7 carriers) of the carrier group and 37.50% (6/16 controls) of the control group were heterozygous for the +861 G>A polymorphism. The distribution of allele frequencies and genotypes of HBA2 between carrier and control samples were analyzed and it is seen that the distribution of allele frequencies and that of genotypes were not statistically significant between carrier and control samples (P-value=0.4131, P-value=0.366, respectively). HBA2 +861 G>A nucleotide substitution is a neutral polymorphism previously reported in other populations. This is the first report in Turkish population.

p300 and cyclic AMP response element-binding protein (CBP) are adenoviral E1A-binding proteins involved in multiple cellular processes, and function as transcriptional co-factors and histone acetyltransferases. Germline mutation of CBP results in Rubinstein-Taybi syndrome, which is characterized by an increased predisposition to childhood malignancies. Furthermore, somatic mutations of p300 and CBP occur in a number of malignancies. Chromosome translocations target CBP and, less commonly, p300 in acute myeloid leukemia and treatment-related hematological disorders. p300 mutations in solid tumors result in truncated p300 protein products or amino-acid substitutions in critical protein domains, and these are often associated with inactivation of the second allele. A mouse model confirms that p300 and CBP function as suppressors of hematological tumor formation. The involvement of these proteins in critical tumorigenic pathways (including TGF-beta, p53 and Rb) provides a mechanistic route as to how their inactivation could result in cancer.