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D K Bowden

Publications and source records attributed to D K Bowden.

At least 37 records · Page 2Linked to original sources
PubMed1988

Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C).

Data on the distribution of beta thalassemia among over 6,000 Melanesians reveals a major difference in the carrier rates between populations in the malarious coastal regions of New Guinea and those living in the historically malaria-free Highlands. The island of Maewo in Vanuatu has a particularly high incidence of beta + thalassemia associated with a single restriction enzyme haplotype. Direct cloning into a plasmid vector and sequence analysis demonstrate that the mutation is a G to C transversion at position 5 of intron 1 of the beta-globin gene. Oligonucleotide probe surveys indicate that this variant accounted for all cases of beta thalassemia studied from Maewo. It is also common in coastal Papua New Guinea where haplotype and oligonucleotide probe data suggest that the molecular basis of beta thalassmia is more heterogeneous.

Alleles↗
PubMed1987

Ahaptoglobinaemia in Melanesia: DNA and malarial antibody studies.

To assess the relative contributions of genetic and acquired factors, particularly malaria, to the high frequencies of ahaptoglobinaemia found in Melanesia we have performed DNA and malarial antibody studies in a population from Vanuatu. No gene deletion or rearrangement was found on gene mapping in any ahaptoglobinaemic individual and the frequencies of the Hp1 and Hp2 alleles in the ahaptoglobinaemic group were similar to controls. However, antibodies to Plasmodium falciparum were significantly elevated in the ahaptoglobinaemics. These data suggest that malaria rather than genetic factors is the major cause of ahaptoglobinaemia in Melanesia.

Adult↗
PubMed1987

High frequency of beta thalassaemia in a small island population in Melanesia.

A study of the causes of anaemia in the south west Pacific archipelago of Vanuatu has identified one island, Maewo, where the carrier rate for beta thalassaemia exceeds 20%, one of the highest recorded incidences in the world. Homozygous beta thalassaemia is a major cause of infant mortality and a serious drain on health resources on this island. Interactions of beta thalassaemia with various forms of alpha + thalassaemia were common in this population. Coexistent alpha + thalassaemia leads to better haemoglobinised and larger red cells than are seen in simple beta thalassaemia heterozygotes and screening for the latter can only be reliably carried out by Hb A2 estimation.

Female↗
PubMed1987

Different hematologic phenotypes are associated with the leftward (-alpha 4.2) and rightward (-alpha 3.7) alpha+-thalassemia deletions.

We have compared the phenotypes of the two common deletion forms of alpha+-thalassemia by analysis of umbilical cord blood samples from Melanesia. Homozygotes for the leftward, 4.2-kilobase, deletion (-alpha 4.2) had significantly higher levels of Hb Bart's at birth than homozygotes for the rightward, 3.7-kilobase, deletion (-alpha 3.7). Compound heterozygotes for each deletion had intermediate values. Although deletion forms of alpha 0 thalassemia were not found in this survey, nondeletion alpha-thalassemia was present at low frequency. Since the predominant rightward deletion in this population, -alpha 3.7III, entirely removes the alpha 1-gene and the 4.2-kilobase deletion deletes the alpha 2-gene, these data indicate that the alpha 2-globin gene has a higher output than the alpha 1-gene, on single alpha-gene chromosomes.

Chromosome Deletion↗
PubMed1986

A silent deletion in the beta-globin gene cluster.

A survey of the gamma-globin gene region of over 1000 normal individuals revealed a novel 2.5 kb deletion which removes the 5' end of the A gamma-globin gene. Unusually, this deletion in the beta-globin gene cluster is not associated with increased fetal haemoglobin production. Sequence analysis of the deletion endpoints revealed no significant homology at the breakpoint and failed to support a role for a proposed recombination hotspot in IVS-2 in the generation of this illegitimate recombination event. The existence of small "silent" deletions in the beta-globin gene cluster emphasizes the importance of deletion size in altering expression of the fetal globin genes.

Base Sequence↗
PubMed1986

Chromosomes with one, two, three, and four fetal globin genes: molecular and hematologic analysis.

Analysis of DNA from 852 Island Melanesians has revealed a high frequency of single- and triple-gamma-globin genes in this population. Homozygotes for triple- and single-gamma genes have normal hematologic findings, normal hemoglobin F (HbF) levels, and when there is coexisting alpha thalassemia, appropriate levels of Bart's Hb (gamma 4) at birth. In addition, we have identified an individual with a quadruple-gamma gene chromosome who also has a normal HbF level. All single-gamma genes were A gamma, all triple-gamma genes G gamma G gamma A gamma, and the quadruple-gamma gene G gamma G gamma G gamma A gamma. Analysis of G gamma:A gamma ratios in cord bloods and HbF levels in adults showed that these additional gamma genes are expressed and are down regulated appropriately by the fetal to adult Hb switch. Analysis of the restriction enzyme haplotypes of these various chromosomes indicates that intrachromosomal cross-overs are more likely to have produced these variants than interchromosomal recombination events.

Adult↗
PubMed1986

A population genetic survey of the haptoglobin polymorphism in Melanesians by DNA analysis.

We have determined the haptoglobin (Hp) genotypes of 831 Melanesians from Vanuatu, Papua New Guinea, and New Caledonia by Southern blot analysis of DNA extracted from umbilical cord and peripheral blood samples. There was complete agreement between these genotypes and the protein phenotype in cases where both were determined, and genotyping was possible in cases where no serum haptoglobins were measurable. Subtyping of Hp1 alleles using restriction enzymes showed that Melanesians, like Mongoloids and Australian Aboriginals, have only the Hp1S allele. Three cases of Hp Johnson were found in Vanuatu, and further restriction mapping supported a partial gene triplication model for the structure of this variant. We also report a new common BclI restriction enzyme polymorphism upstream of the Hp1 gene. The advantages of using DNA for haptoglobin typing are discussed.

Alleles↗
PubMed1985

Relative roles of genetic factors, dietary deficiency, and infection in anaemia in Vanuatu, South-West Pacific.

Hypochromic anaemia is very common among the island populations of Vanuatu in the South-West Pacific. Results of a large-scale survey show that, unexpectedly, this form of anaemia is seldom due to iron deficiency or coexistent parasitic disease. Rather, it results from a previously unsuspected high incidence of alpha-thalassaemia which has been identified only by application of DNA analysis to the populations studied. These findings suggest that hypochromic anaemia in tropical or subtropical populations should not necessarily be attributed to iron deficiency; detailed studies of iron status should be carried out before major dietary changes or fortification of food with iron are implemented.

Adolescent↗
PubMed1985

Analysis of genetic variation in two human thyroxine-binding plasma proteins by immunodetection after isoelectric focusing.

An immunological method for the detection of two thyroxine-binding plasma proteins, thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA), following polyacrylamide gel isoelectric focusing is described. Both proteins show complex electrophoretic patterns, attributable to post-translational glycosylation, which are affected by unfavourable conditions of sample storage. No genetic variants of TBG or TBPA were encountered in a study of N. European individuals (n = 50). The X-linked TBG polymorphism, previously detected using a radiolabelled ligand binding technique in Pacific Islanders, was, however, demonstrable by our new immunological method in a previously untested population (n = 139) from the island of Maewo in Vanuatu.

Gene Frequency↗
PubMed1985

Melanesians and Polynesians share a unique alpha-thalassemia mutation.

Several genetic markers that provide information on population migrations and affinities have been detected by studies of proteins and cellular antigens in blood. Analysis of DNA polymorphisms promises to yield many further population markers, and we report here the distribution of a new alpha-globin gene deletion (-alpha 3.7 III) detected by a restriction enzyme mapping. This is found frequently in Melanesians and Polynesians but not in five other populations in which alpha-thalassemia is prevalent. We used restriction enzyme haplotype analysis to support a single origin for this mutation and propose that it is a useful population marker. Its geographical distribution supports a route through Island Melanesia for the colonizers of Polynesia.

Chromosome Deletion↗
PubMed1984

Independent recombination events between the duplicated human alpha globin genes; implications for their concerted evolution.

We have examined the molecular structure of the human alpha globin gene complex from individuals with a common form of alpha thalassaemia in which one of the duplicated pair of alpha genes (alpha alpha) has been deleted (-alpha 3-7). Restriction mapping and DNA sequence analysis of the mutants indicate that different -alpha 3.7 chromosomes are the result of at least three independent events. In each case the genetic crossover has occurred within a region of complete homology between the alpha 1 and alpha 2 genes. Since the -alpha chromosomes may reflect the processes of crossover fixation and gene conversion between the two genes, their structures may provide some insight into the mechanism by which the concerted evolution of the human alpha globin genes occurs.

Base Sequence↗
PubMed1982

Human rotavirus infection in Efate, Vanuatu.

Serum and fecal samples collected from children with gastroenteritis and healthy children and adults living in Efate, Vanuatu (formerly the New Hebrides), were tested for the presence of human rotavirus antigen or antibody by electron microscopy and enzyme-linked immunosorbent assay. Virtually every subject was found to have detectable levels of antibody and age-specific studies showed that primary infections occur early in life. Human rotavirus was demonstrated to be the cause of an outbreak of gastroenteritis among children which occurred between August and September 1980, although it had not been detected in the population in the preceding 13 months. Epidemics of human rotavirus-associated gastroenteritis appear to occur every 2nd year in this population.

Adolescent↗
PubMed1982

Coronavirus-like particles and other agents in the faeces of children in Efate, Vanuatu.

Between June 1979 and July 1980, faecal specimens were collected from 100 children in Efate, Vanuatu, and examined for the presence of virus-like particles by direct negative staining electron microscopy. Of the children, 40 were hospital patients 22 of whom had gastroenteritis and 18 had other illnesses. The remaining 60 children were apparently healthy controls. Coronavirus-like particles were the most common agents encountered and were detected in approximately 20% of all three groups of children. Particles with the morphological features of calicivirus, astrovirus, adenovirus and parvovirus were also detected.

Adenovirus Infections, Human↗
PubMed1982

alpha-globin gene deletions associated with Hb J Tongariki.

Three identical alpha + thalassemia genes, one of which always carried the Hb J Tongariki mutation, have been observed in Vanuatuans. Despite the fact that at least two of them have arisen by different types of crossover event, the expression of all three haplotypes is identical.

Chromosome Deletion↗
PubMed1981

A novel rearrangement of the human beta-like globin gene cluster.

The first example of a duplication involving the human beta-like globin genes has been characterised in DNA from a native of Vanuatu. Restriction endonuclease mapping has shown that a 5 kb insert of DNA in the gamma-delta-beta gene cluster is due to duplication of the Ggamma-globin gene and results in a new rearrangement 5'-epsilon-Ggamma-Ggamma-Agamma-delta-beta-3'.

Adult↗