Alpha thalassemia and alpha-MRE haplotypes in Uruguayan patients with microcytosis and hypochromia without anemia

Abstract

Alpha thalassemia is the most common genetic disorder across the world, being the α- 3.7 deletion the most frequent mutation. In order to analyze the spectrum and origin of alpha thalassemia mutations in Uruguay, we obtained a sample of 168 unrelated outpatients with normal hemoglobin levels with microcytosis and hypochromia from two cities: Montevideo and Salto. The presence of α-thalassemia mutations was investigated by gap-PCR, restriction endonucleases analysis and HBA2 and HBA1 genes sequencing, whereas the alpha-MRE haplotypes were investigated by sequencing. We found 55 individuals (32.7%) with α-thalassemia mutations, 51(30.4%) carrying the -α 3.7 deletion, one with the -α 4.2 deletion and three having the rare punctual mutation HBA2:c.-59C>T. Regarding alpha-MRE analysis, we observed a significant higher frequency of haplotype D, characteristic of African populations, in the sample with the -α 3.7 deletion. These results show that α-thalassemia mutations are an important determinant of microcytosis and hypochromia in Uruguayan patients with microcytosis and hypochromia without anemia, mainly due to the -α 3.7 deletion. The alpha-MRE haplotypes and the α-thalassemia mutations spectrum suggest a predominant, but not exclusive, African origin of these mutations in Uruguay.

Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion

“…After determining that the specific HS-40 haplotype D and genotypes AD, BD, and DD, are associated with the presence of the 3.7 kb α-thalassemia deletion in the Portuguese population, we aimed to investigate the ancestry of this deletion in this population. Initially, these genotypes were only reported in African people [ 15 , 16 ], however more recently, they were also detected in Uruguayans [ 30 ]. In the two populations, these genotypes have been found mostly in individuals with the 3.7 kb deletion.…”

“…Multiple correspondence analysis was performed in order to better visualize the similarities between the Portuguese population and other populations [ 15 , 16 , 30 , 31 ]. This analysis showed that the Portuguese individuals who do not have α-thalassemia (PRT Normal) are grouped with other European populations, while samples with the 3.7 kb deletion (PRT -α3.7/αα and PRT -α3.7/-α3.7) are isolated from these and found to be more closely related to the African population (Fig.…”

“…AFR: African; BRA: Brazilian; CHN: Chinese; DEU: Dutch; IDN: Indonesian; IND: Indian; IRN: Iranian; ITA: Italian; PRT: Portuguese; PYG: Pygmies; URY: Uruguayan. All the genotypes from foreign populations were collected from [ 15 , 16 , 30 , 31 ]. The Portuguese populations investigated in this study are marked as PRT normal, PRT -α 3.7 /αα, and PRT -α 3.7 /-α 3.7 …”

“…The Portuguese population is predominantly composed of haplotype A (60%) and haplotype B (30%), according to the 222 alleles analyzed for the HS-40 region sequence. Similarly, haplotype A was also reported as predominant in the Italian, Indonesian, Chinese, East Indian, Bantu-speaking-Africans, Brazilian Indians, and Uruguayan populations, with frequencies ranging from 56 to 87% [ 15 , 16 , 30 ], while haplotype B was found to be predominant exclusively in the Dutch population (57%) [ 15 ]. For the other populations indicated above, the haplotype B frequencies are lower and range between 13 and 43% [ 15 , 16 , 30 ].…”

“…Similarly, haplotype A was also reported as predominant in the Italian, Indonesian, Chinese, East Indian, Bantu-speaking-Africans, Brazilian Indians, and Uruguayan populations, with frequencies ranging from 56 to 87% [ 15 , 16 , 30 ], while haplotype B was found to be predominant exclusively in the Dutch population (57%) [ 15 ]. For the other populations indicated above, the haplotype B frequencies are lower and range between 13 and 43% [ 15 , 16 , 30 ]. On the other hand, haplotype D is characteristic of Bantu-speaking Africans (16%) and Pygmies from the Central African Republic (5%), being nearly absent in others populations [ 15 ].…”