In a family of Indian origin we have identified a deletion of two bases at the polyadenylation signal sequence of the alpha 2-globin gene (AATAAA-->AATA). Three individuals heterozygous for this mutation display an alpha o-thalassaemia-like phenotype. Single-stranded conformation analysis and automatic sequencing showed no additional mutations in either alpha 1- or alpha 2-globin genes. A previously described polyadenylation sequence mutation (AATAAA-->AATAAG), alpha TSaudi alpha, causes HbH disease in homozygotes. In this study the patients heterozygous for the AATA(-AA) mutation show a similar phenotype observed in the alpha TSaudi alpha heterozygotes. This confirms the observation that the inefficient transcriptional termination due to mutations of the polyadenylation sequence of the alpha 2-gene might interfere with the alpha 1-gene expression.
We describe here the screening of a small group of apparently healthy individuals belonging to the tribal communities of Koya Dora and Konda Reddi. A remarkably high incidence of deletion and nondeletion alpha + thalassemia mutants has been found with allele frequencies and distributions characteristic to each tribe. We have confirmed the strict relationship between Hb S levels and the number of alpha globin genes in double heterozygotes for the S gene and alpha thalassemia. In this population sample we did not find either heterozygous carriers of alpha 0 thalassemia (deletion of both alpha genes in "cis") or individuals showing hemolytic anemia due to inactivation of three alpha-globin genes (Hb H disease). Selection by malaria is most probably responsible for the prevalence of the various alpha + thalassemia haplotypes among the two tribal populations of Andhra Pradesh.
A total of 811 young people (16–27 years) of both sexes were studied in a health screening program during which multiple biochemical, haematological, and physical variables were measured. In addition, the phenotypes of these subjects were established at 22 polymoφhic gene loci. Analysis of variance by several methods showed no more statistically significant differences than would be expected by chance in any of these variables between persons of distinct phenotypes apart from those associations which have been delineated previously (e.g., cholesterol and ABO blood group, alkaline phosphatase and ABO blood group). More interesting findings were those which related the variables among themselves. Thus, weight, serum protein level, and red blood cell measurements were found to be positively correlated to a substantial extent with blood pressure readings.
A group of 202 unrelated Italians were screened for α1-antitrypsin using agarose-acrylamide electrophoresis and isoelectric focusing. The S and F gene frequencies were comparable to those found among Greeks and North European populations, but they differed considerably from the frequencies found among Spaniards and Portuguese. The other gene frequencies appeared to be comparable to other populations studied.
Severe haemolytic anaemia with hyperbilirubinaemia and erythroblastaemia was observed in nine newborn infants belonging to one large family. One infant was still-born, two died shortly after birth, five recorded after receiving one or more exchange transfusions and one improved without transfusional therapy. In four out of six newborns whose bilirubin levels were determined, a mixed hyperbilirubinaemia was found with high concentrations of both free and conjugated bilirubin. At the end of the first year of life the surviving children, although in satisfactory general condition, showed a mild microcytic hypochromic anaemia with decreased red cell osmotic fragility and morphological abnormalities of the erythrocytes consisting of microcytosis, anisopoikilocytosis and target cells. The serum iron levels were normal. The same haematological picture was also present in those parents of the affected children that are members of this family; these adult had normal levels of Hbs A2 and F. Incorporation of [3H]leucine into the globin chains of two adults with this syndrome revealed a reduced beta-chain synthesis (beta/alpha ratio of 0 . 49 and 0 . 53, respectively). In the two infants available for this investigation, reduced gamma-chain production was found shortly after birth. In parallel with the switch from fetal to adult haemoglobin, the deficient gamma-chain production was replaced by a similar reduction of beta-chain synthesis. These results suggested, therefore, a combined deficiency of gamma- and beta-chain production. The normal levels of Hb A2 were compatible with a defective delta-chain synthesis as well. Analysis with restriction enzymes had shown previously a large deletion, comprising gamma and delta genes, in one of the chromosomes of the affected individuals. The same procedure had established that, in spite of the defective beta-chain production, the beta-globin structural gene is intact.
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