44 research outputs found
α-thalassaemia
Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia
Pre-Caucasoid and Caucasoid genetic features of the Indian population, revealed by mtDNA polymorphisms
About 70 individuals from Punjab were examined for some mtDNA polymorphisms, namely, the RFLPs of the six classical enzymes (HpaI, BamHI, HaeII, MspI, AvaII, and Hin-cII) and for the sites AluI(7,025), DdeI(10,394), and AluI(10,397). The AluI(7,025) polymorphic site was also investigated in 96 Indians from Uttar Pradesh and Andhra Pradesh and in 163 Mediterranean Caucasoids. Moreover, 30 Indian DdeI(10,394)Alu(10,397) (++) mtDNAs were typed by the "high-resolution restriction analysis" with 14 endonucleases to estimate their divergence time. The results obtained are the following: (1) The RFLPs analysis has displayed some Caucasoid types as in Indians of Uttar Pradesh; (2) the AluI(7,025) (-) allele, which defines the most frequent Caucasoid-specific lineage (haplogroup H), ranges from 18% to 45% in the Mediterranean Caucasoids, whereas it has shown low frequencies in Punjab (6.0%) and in Uttar Pradesh (1.8%) and was not found in Andhra Pradesh; (3) the DdeI(lO,394)AluI(10,397) (+ +) haplotype, which although previously was considered an East Asian marker (haplogroup M) and was found very frequently in India, is also frequent in Punjab (27%); this frequency is, however, much lower than in Uttar Pradesh (49%) and in Andhra Pradesh (74%), and a gradient decreasing from south to north is therefore observed; (4) the divergence time of the Indian DdeI(10,394)AluI(10,397) (++) mtDNAs has been estimated to be 30,250-60,500 years, a value that is compatible with that of the homologous East Asian lineage. These results strongly support the hypothesis that the DdeI(10,394)AluI(10,397) (++) haplotype predated the Indo-European invasion and probably the split between proto-Indians and proto-Orientals. Its frequency cline well reflects the major influence of Indo-Europeans in the north and in the center of India
MtDNA provides the first known marker distinguishing proto-Indians from the other Caucasoids; it likely predates the diversification between Indians and Orientals.
The concomitant presence of the two sites Ddel at 10,394 and Alul at 10,397 has been considered an East-Asian marker of ancient origin (it was also observed in Australians, Melanesians and Native Americans). Unexpectedly, it was found in more than 50% of Indians (133 Hindus and 30 Tribals) who had shown Caucasoid characteristics not only at nuclear DNA but also at mtDNA level. It can therefore no longer be considered an exclusively East-Asian mtDNA feature. The analysis of more than 200 Caucasoids, mainly from the Mediterranean basin, showed that it is only sporadically present in these people. Thus it represents the first known marker which distinguishes Indians from the other Caucasoids. The lack of this marker in Indian mtDNA molecules carrying Caucasoid characteristics suggests that it predates the invasion of India by speakers of an Indo-European language and, if it is valid to extrapolate from Near Eastern data, the arrival in India of the farmers who spread the Dravidian language. If this polymorphism had a common origin in both Orientals and Indians, it should also predate the diversification between ancient Indians and Mongoloids
alpha-thalassaemia as a result of a novel splice donor site mutation of the alpha1-globin gene.
Hb Aghia Sophia [alpha 62(E11)Val -> 0 (alpha 1)], an “in-frame” deletion causing alpha-thalassemia
In this report we describe a case of Hb H disease due to the interaction
of the - -((MED I)) deletion with a new alpha(+)-thalassemia
determinant. The molecular analysis of the proband’s genomic DNA was
carried out by polymerase chain reaction amplification and sequencing of
both alpha genes of the alpha(+)-thalassemia chromosome and revealed a
deletion of codon 62 of the alpha 1 gene. This DNA triplet codes for a
valine residue at the E11 alpha helix, which is located in the interior
of the heme pocket. Substitutions of valine E11 with other amino acid
residues in the alpha as well as beta polypeptide chains lead, in the
heterozygous carrier, either to Hb M disease or to congenital
non-spherocytic hemolytic anemia. We assume that the deletion of valine
at alpha 62(E11) disrupts the conformation of the alpha chain to such an
extent that the mutated subunit is rapidly removed by proteolysis. The
final result is an alpha-thalassemia phenotype rather than an unstable
hemoglobin syndrome. This conclusion is supported by the apparent
absence of an abnormal alpha chain in the peripheral blood of the
patient