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  • 1
    ISSN: 1573-4927
    Keywords: orangutan ; hemoglobin F ; vγ chain ; nonallelic genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Previous studies suggested that orangutans have nonallelic structural genes for their γ chains, because either a threonyl or an alanyl residue may occupy position 135. Further investigation has now detected that position 75 may have either an isoleucyl or a valyl residue. From available evidence, the isoleucyl and threonyl residues are in one chain and the valyl and alanyl in the other. Orangutans appear to be homozygous for the two types of nonallelic genes.
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  • 2
    ISSN: 1573-4927
    Keywords: hereditary persistence of fetal hemoglobin ; different types of HPFH ; Gγ:Aγ ratio ; restriction endonucleases ; DNA ; in vitro chain synthesis ; family data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Restriction endonuclease analyses of DNA from one Black GγAγ-HPFH homozygote and four Black and one Indian GγAγ-HPFH heterozygotes have identified three different HPFH types which are the result of large deletions including the δ and β genes. Two of the types are comparable to those characterized previously, but the third, which is present in the Indian heterozygote, shows a distinct difference in the size of the deletion. The 5′ end point of the deletion in this type III GγAγ-HPFH extends 0.5–1.0 kb beyond the 5′ end point of one of the Black types of HPFH (type I). Each of the three types is associated with a distinct ratio between the Gγ and the Aγ chains, an observation supported by family data. The highest ratio is found in the heterozygote with the Indian type III GγAγ-HPFH, with 69.3% Gγ chains, while the averages for the other types were 50.7% Gγ (type I) and 32.3% Gγ (type II).
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  • 3
    ISSN: 1573-4927
    Keywords: fetal hemoglobin ; βo-thalassemia ; γ globin gene triplication ; γ globin gene deletion ; haplotypes ; silent β-chain variant ; F-Sardinia ; the AγT chain ; —Gγ—Gγ— and —Aγ—Aγ— arrangements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Fetal hemoglobin analysis and globin gene mapping have identified one type of βo-thalassemia and four different γ globin gene arrangements among newborn babies from the northern part of Sardinia. The βo-thalassemia with a nonsense mutation at codon 39 was found on two chromosomes, each with a distinct pattern of polymorphic restriction sites; one had the AγT (Aγ75 Ile → Thr) mutation, while the second did not. Four closely related haplotypes were identified for chromosomes with the AγT mutation. The γ-thalassemia heterozygosity with the —GAγ— hybrid gene fell into two categories. One apparently originated through crossing-over between mismatched chromosomes characterized by the most common haplotype, while the other had polymorphisms resembling those of a less frequently occurring chromosome. Chromosomes with the —Gγ—AGγ—Aγ— triplication had polymorphic sites to be expected for this condition, being complimentary to the —GAγ— thalassemias. Of the two additional γ globin gene variations the —Gγ—Gγ— arrangement was associated with the chromosome with the most commonly occurring haplotype, while the chromosome with the —Aγ—Aγ— arrangement had a haplotype characteristic for that with the AγT mutation, which identified an —Aγ—AγT— arrangement. The incidental discovery of a silent β-chain mutant, Hb Hamilton, with the Val → Ile substitution at position β11, in five newborns was also reported.
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  • 4
    ISSN: 1573-4927
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract An abnormal human fetal hemoglobin not only may be either aGγ- or anAγ-chain variant but also may be present in a different proportion of the total fetal hemoglobin.Gγ-Chain variants contribute either about one-fourth or one-eighth to the total production of HbF in the heterozygote, whereas theAγ-chain variants approximate either one-eighth or one-sixteenth of the total HbF. These observations may indicate the presence of four nonallelic Hbγ structural genes (termed $$Hb_{_m^G \gamma } ,Hb_{_1^G \gamma } ,Hb_{_m^A \gamma } ,andHb_{_1^A \gamma } $$ ) which produce γ chains in an approximate ratio of 4 : 2 : 2 : 1. HbF Malta I is considered to be the product of a mutant of the $$Hb_{_m^G \gamma } $$ locus, an undefined HbFx that of the $$Hb_{_1^G \gamma }$$ locus, HbF Hull and HbF Jamaica products of mutated $$Hb_{_m^A \gamma }$$ loci, and the newly discovered HbF Malta II a mutant of the $$Hb_{_1^A \gamma }$$ gene.
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  • 5
    ISSN: 1573-4927
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Peptide γCB-3 is the indicator of the presence and activity of nonallelic structural genes for the human γ-chain. An equivalent peptide has been isolated from the HbF of the marmoset (Saguinus fuscicollis), the rhesus monkey (Macaca mulatta), the orangutan (Pongo pygmaeus), and the gorilla (Gorilla gorilla gorilla). The sequence of γCB-3 from the marmoset and the rhesus monkey, although different from that of human γCB-3, gives no evidence of heterogeneity of the HbF. However, the HbF of the rhesus monkey is itself heterogeneous, and there probably is a difference in another part of the γ-chain. The γCB-3 peptide of the orangutan is definitely heterogeneous: the heterogeneity is in position 135, however, rather than in position 136 as in human γCB-3. The gorilla has the same type of heterogeneity at position 136 as does the human, but the proportions of the two types of chains might differ in the two species.
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  • 6
    ISSN: 1573-4927
    Keywords: HPFH homozgote ; γ-chain type ; globin chain synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Two sons of a previously reported Ghanaian homozygote for the hereditary persistence of fetal hemoglobin (HPFH) (Ringelhann et al., 1970) also are HPFH homozygotes. In addition, another unrelated adult Ghanaian homozygote has been detected. All of these Ghanaian homozygotes as well as three American Black HPFH homozygotes have the G γ A γ type of HPFH with a G γ to A γ ratio of about 3:2, in contrast to an Asiatic Indian homozygote who has the G γ type. Globin chain synthesis in HPFH homozygotes is unbalanced, with a γ/α ratio of 0.6 or less, whereas it is balanced in heterozygotes according to most reports.
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  • 7
    ISSN: 1573-4927
    Keywords: radioimmunoassay ; hemoglobin F variants ; hemoglobinopathies ; γ chain loci
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A variant of fetal hemoglobin (Hb F-Malta-I) has been detected and quantitated in adult blood with a sensitive radioimmunoassay employing monospecific anti-sera. The concentration of Hb F-Malta-I was 0.002–0.05%, with an average value of 0.011%. The ratio of Hb F-Malta-I/Hb F in adults was about 4.8%, compared to a ratio of about 27% in the newborn. Since the F-Malta-I variant is a product of a mutated Gγ locus, which is one of the nonallelic structural genes directing the γ chain synthesis, its presence in blood of adults shows that the synthesis of this gene is not completely suppressed after birth, as was previously suggested.
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  • 8
    ISSN: 1573-4927
    Keywords: Hb α chain variants ; α-thalassemia ; Hb synthesis ; Hb genetics ; posttranslational control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The production of five α chain variants (Hb G-Georgia, Hb St. Luke's, Hb Lloyd, Hb Montgomery, and Hb G-Philadelphia) in heterozygotes was evaluated through hematological observations, hemoglobin quantification, and biosynthetic studies. All heterozygotes for Hb St. Luke's and Hb Lloyd and most heterozygotes with Hb G-Georgia and Hb Montgomery had normal hematology and average σα/β values of about 1.1. They were assigned a normal genotype (ααG/αα), although the proportions of Hb St. Luke's and Hb G-Georgia were low (10 to 13%) and those of Hb Lloyd and Hb Montgomery twice as high (20%). Data from short-term incubations confirmed this genotype for some of these heterozygotes. Isolated Hb St. Luke's and Hb G-Georgia gave low αG/β values (0.2 and 0.3) indicating that these Hb variants were defective at the level of Hb assembly. Isolated Hb Montgomery and Hb G-Philadelphia, however, gave higher αG/β values of 0.6 and 0.8, respectively. A second type of variability existed among Hb G-Georgia (20 vs. 13%), Hb Montgomery (28 vs. 20%), and Hb G-Philadelphia (47 vs. 34%) heterozygotes, in whom the levels of Hb G differed. The occurrence of higher levels of these three α chain heterozygosities was associated with hematological or biosynthetic evidence of a mild or moderate α chain deficiency due to an α-thalassemia-2 heterozygosity (ααG/α0α or α0αG/αα) or a homozygosity (α0αG/α0α), respectively.
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  • 9
    ISSN: 1573-4927
    Keywords: DNA sequence ; human θ1-globin gene ; cloning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We have cloned and sequenced the human θ1-globin gene. The nucleotide sequence and organization of the human θ1 gene (exons, introns, promoter, and polyadenylation signals) are similar to those reported for the orangutan θ1-globin gene. If these genes are functional, the sequences of their θ1-globin chains would differ by only one amino acid residue (at position 137).
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  • 10
    ISSN: 1573-4927
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A survey of blood specimens from 146 American bison, Bison bison, showed the presence of two hemoglobin phenotypes because the ratio of the two normally occurring hemoglobins differed. These two hemoglobins, which are readily identified by their electrophoretic properties and are referred to as Hb-fast and Hb-slow, have been found in all bison. Chromatographic analyses showed that in the majority of animals the ratio between the relative amounts of Hb-fast and Hb-slow was about 60:40, but in three animals from South Dakota this ratio was about 80:20. Structural studies were made on the α chains of Hb-fast and Hb-slow from one animal with the 60:40 ratio and on those from a second animal with the 80:20 ratio. Four types of α chains could be demonstrated which differ from each other by at least one to three amino acid residues. It is suggested that these four α-chain types are the products of two nonallelic Hb α structural genes and their alleles.
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