Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene duplication is one of the basic processes underlying evolutionary changes. The gamma-chains of human foetal haemoglobin is coded by multiple structural genes. The delta-chains of Hb A2 can be regarded as a duplication of the beta-locus. We have presented the first evidence for the presence of two major alpha-chain loci in man. The alpha-gene appears to have duplicated recently, since apart of the single point mutations characterizing Hb J-Buda and Hb G-Pest, the two alpha-gene products seem to be identical. Sensitive immunochemical measurement techniques may reveal structural differences which might escape detection by chemical methods based on differences in charge and/or chromatographic behaviour. Anti-alpha-chain sera recognizing the single amino acid substitution in alphaJ-Buda could be raised in rabbits. The anti-alpha-chain sera were found to be more powerful tools for detecting differences in the primary structure of the chain than the immune sera raised against the whole tetramer. None of the immune sera could reliably differentiate Hb G-Pest from Hb A1. The relative strength of complement fixation of the alpha-chains from haemoglobin A1 F and A2 was compared by hybridizing these human haemoglobins with caninehaemoglobin and measuring the quantitative complement fixation of the different hybrids with anti-Hb A1 and anti-alphaA1 rabbit immune sera. No antigenic difference among the alpha-chains from haemoglobins A1, A2 and F could be detected by this method either with anti-A1 or with anti-alphaA1 sera. These results do not exclude the possibility of conformational differences between the alpha-chains in native Hb A and Hb F. The antigenic activity of the alpha-chains of Hb A from normal subjects (alphaA1) and of the alpha-chains of Hb A from a double heterozygote for alphaJ-Buda and alphaG-Pest (alphaA1) were compared by the complement fixation technique. Definite differences could be detected in the relative strength of complement fixation by alphaA1 and alphaA1 with anti-alphaA1 serum. Final decision as to whether alpha-chain duplication is a universal phenomenon or whether it is restricted to only a part of mankind cannot be drawn until the presence of a silent alpha-thalassaemia gene is not excluded in some debated cases by reliable chemical methods. Measurement of alpha-globin genes in Hb H disease with cDNA enriched in alpha-globin sequences provided direct evidence that a non-thalassaemic subject has to have at least four alpha-globin genes per diploid cell.
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PMID:Duplication of the haemoglobin alpha-gene. 6 38

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, alphaalphaNcoI, alphaIcalpha and alphaTSaudialpha) was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(alphaalpha)T]. Among the 27 patients with structural alterations, 15 (of Italian descent) had Hb Hasharon (alpha47Asp-->His) associated with the -alpha3.7 deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (alpha53Ala-->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb Stanleyville-II (alpha78Asn-->Lys) associated with the alpha+-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha74Asp-->Asn), 1 (Caucasian) was heterozygous for Hb Kurosaki (alpha7Lys-->Glu), 1 (Caucasian) was heterozygous for Hb Westmead (alpha122His-->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha26Ala-->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.
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PMID:alpha-globin genes: thalassemic and structural alterations in a Brazilian population. 1097 35