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A J Boyce

Publications and source records attributed to A J Boyce.

At least 19 recordsLinked to original sources
PubMed2006

Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa.

Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.

Journal Article↗
PubMed2000

Polymorphism and divergence in the beta-globin replication origin initiation region.

DNA sequence polymorphism and divergence was examined in the vicinity of the human beta-globin gene cluster origin of replication initiation region (IR), a 1.3-kb genomic region located immediately 5' of the adult-expressed beta-globin gene. DNA sequence variation in the replication origin IR and 5 kb of flanking DNA was surveyed in samples drawn from two populations, one African (from the Gambia, West Africa) and the other European (from Oxford, England). In these samples, levels of nucleotide and length polymorphism in the IR were found to be more than two times as high as adjacent non-IR-associated regions (estimates of per-nucleotide heterozygosity were 0.30% and 0.12%, respectively). Most polymorphic positions identified in the origin IR fall within or just adjacent to a 52-bp alternating purine-pyrimidine ((RY)n) sequence repeat. Within- and between-populations divergence is highest in this portion of the IR, and interspecific divergence in the same region, determined by comparison with an orthologous sequence from the chimpanzee, is also pronounced. Higher levels of diversity in this subregion are not, however, primarily attributable to slippage-mediated repeat unit changes, as nucleotide substitution contributes disproportionately to allelic heterogeneity. An estimate of helical stability in the sequenced region suggests that the hypervariable (RY)n constitutes the major DNA unwinding element (DUE) of the replication origin IR, the location at which the DNA duplex first unwinds and new strand synthesis begins. These findings suggest that the beta-globin IR experiences a higher underlying rate of neutral mutation than do adjacent genomic regions and that enzyme fidelity associated with the initiation of DNA replication at this origin may be compromised. The significance of these findings for our understanding of eukaryotic replication origin biology is discussed.

Animals↗
PubMed1999

Minisatellite mutational processes reduce F(st) estimates.

We have used a new method for binning minisatellite alleles (semi-automated allele aggregation) and report the extent of population diversity detectable by eleven minisatellite loci in 2,689 individuals from 19 human populations distributed widely throughout the world. Whereas population relationships are consistent with those found in other studies, our estimate of genetic differentiation (F(st)) between populations is less than 8%, which is lower than comparative estimates of between 10%-15% obtained by using other sources of polymorphism data. We infer that mutational processes are involved in reducing F(st) estimates from minisatellite data because, first, the lowest F(st) estimates are found at loci showing autocorrelated frequencies among alleles of similar size and, second, F(st) declines with heterozygosity but by more than predicted assuming simple models of mutation. These conclusions are consistent with the view that minisatellites are subject to selective or mutational constraints in addition to those expected under simple step-wise mutation models.

Alleles↗
PubMed1998

The population genetics of the haemoglobinopathies.

The haemoglobinopathies are the commonest single-gene disorders known, almost certainly because of the protection they provide against malaria, as attested by a number of observations. The geographical distributions of malaria and haemoglobinopathies largely overlap, and microepidemiological surveys confirm the close relationship between them. For two of the commonest disorders, haemoglobin S and alpha(+)-thalassaemia, there is also good clinical evidence for protection against malaria morbidity. However, not all the evidence appears to support this view. In some parts of the world malaria and haemoglobinopathies are not, and never have been, coexistent. It is also difficult to explain why the majority of haemoglobinopathies appear to be recent mutations and are regionally specific. Here we argue that these apparent inconsistencies in the malaria hypothesis are the result of processes such as genetic drift and migration and of demographic changes that have occurred during the past 10,000 years. When these factors are taken into account, selection by malaria remains the force responsible for the prevalence of the haemoglobinopathies.

Genetics, Population↗
PubMed1997

Seroprevalence of Borrelia burgdorferi in dogs in Alabama, USA.

A random sample of private small-animal practices in Alabama submitted sera from dogs with known tick contact. A total of 579 samples from the three geographic regions of the state were collected (58% of the targeted sample size). Sera were screened for antibodies to Borrelia burgdorferi using an indirect fluorescent antibody (IFA) test which had a sensitivity and specificity of greater than 90%. Anti-B burgdorferi titers of > or = 1:64 were considered to be positive, based on results from B. burgdorferi-inoculated dogs. Ten of the 579 samples (1.7%) were positive, and titers ranged from 1:64 to 1:512. Seropositive dogs were found throughbout the state, and there was no significant difference in seroprevalence by region (Mantel-Haenszel chi 2, P = 0.85). These results indicate that the seroprevalence for canine Lyme disease in Alabama is low and that use of the canine Lyme disease vaccine is not justified.

Alabama↗
PubMed1995

High diversity of alpha-globin haplotypes in a Senegalese population, including many previously unreported variants.

RFLP haplotypes at the alpha-globin gene complex have been examined in 190 individuals from the Niokolo Mandenka population of Senegal: haplotypes were assigned unambiguously for 210 chromosomes. The Mandenka share with other African populations a sample size-independent haplotype diversity that is much greater than that in any non-African population: the number of haplotypes observed in the Mandenka is typically twice that seen in the non-African populations sampled to date. Of these haplotypes, 17.3% had not been observed in any previous surveys, and a further 19.1% have previously been reported only in African populations. The haplotype distribution shows clear differences between African and non-African peoples, but this is on the basis of population-specific haplotypes combined with haplotypes common to all. The relationship of the newly reported haplotypes to those previously recorded suggests that several mutation processes, particularly recombination as homologous exchange or gene conversion, have been involved in their production. A computer program based on the expectation-maximization (EM) algorithm was used to obtain maximum-likelihood estimates of haplotype frequencies for the entire data set: good concordance between the unambiguous and EM-derived sets was seen for the overall haplotype frequencies. Some of the low-frequency haplotypes reported by the estimation algorithm differ greatly, in structure, from those haplotypes known to be present in human populations, and they may not represent haplotypes actually present in the sample.

Genetic Variation↗
PubMed1994

Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus.

Allelic sequence polymorphism at the beta-globin locus was investigated in a group of 36 Melanesians. A 3-kilobase fragment containing the gene and its flanking regions was sequenced in 60 normal (beta A) and 12 thalassemic (intron 1, position 5, G-->C) chromosomes. Haplotype relationships between linked polymorphisms were derived by allele-specific PCR amplification and sequencing. Seventeen nucleotide polymorphisms and 2 length variants were identified, and these sites segregated as 17 sequence haplotypes in the normal chromosomes. This haplotype diversity is higher than that expected on the basis of the nucleotide polymorphism observed and is probably due to recombination and gene conversion. Nucleotide diversity at synonymous sites in the sample is 0.14%, suggesting an average age of sequence divergence of approximately 450,000 years, consistent with that expected for a neutrally evolving human nuclear locus.

Alleles↗
PubMed1994

VNTR alleles associated with the alpha-globin locus are haplotype and population related.

The human alpha-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5' hypervariable region (HVR) and the more highly polymorphic 3'HVR. Using a combination of RFLP analysis and PCR, we have characterized the 5'HVR and 3'HVR alleles associated with the alpha-globin haplotypes of 133 chromosomes, and we here show that specific alpha-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning approximately 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3'HVR alleles. Earlier studies have shown that alpha-globin haplotype distributions differ between populations; our current findings also reveal extensive population substructure in the repertoire of alpha-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies.

Alleles↗
PubMed1993

Demographic reductions and genetic bottlenecks in humans: minisatellite allele distributions in Oceania.

Polynesians have lower heterozygosities at minisatellite VNTR (Variable Number of Tandem Repeat) loci than have Melanesians; this has been taken as evidence of population-size bottlenecks during the colonisation of Polynesia. We have analysed the allelic distribution of several minisatellite loci in the population of Rapa, a Polynesian island that is known to have undergone a demographic reduction of approximately 95% since first contact with European explores 200 years ago, leaving a surviving population of 120. We found that the minisatellite diversity of this population does not differ significantly from that of other Polynesian populations, and appears consistent with the neutral expectation of diversity assuming the infinite alleles model. This suggests that the demographic crisis that Rapa underwent did not perturb the allele distribution to the extent that the tests used here could detect. Thus we cannot say that a demographic change of this magnitude constitutes a genetic bottleneck detectable at these loci. The reduced diversity seen in Polynesia must therefore be explained either by more severe bottlenecks as might be expected during colonisation, or else by other causes.

Alleles↗
PubMed1993

Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants.

Various processes (selection, mutation, migration and genetic drift) are known to determine the frequency of genetic disease in human populations, but so far it has proved almost impossible to decide to what extent each is responsible for the presence of a particular genetic disease. The techniques of gene and haplotype analysis offer new hope in addressing this issue, and we review relevant studies of three haemoglobinopathies: sickle cell anaemia, and alpha and beta thalassaemia. We show how for each disease it is possible to recognize a pattern of regionally specific mutations, found in association with one or a few haplotypes, that is best explained as the result of selection; other patterns are due to population migration and genetic drift. However, we caution that such conclusions can be drawn in special circumstances only. In the case of the haemoglobinopathies it is possible because a selective agent (malaria) was already suspected, and the investigations could be carried out in relatively genetically homogenous populations whose migratory histories are known. Moreover, some data reviewed here suggest that gene conversion and the haplotype composition of a population may affect the frequency of a mutation, making interpretation of gene frequencies difficult on the basis of standard population genetics theory. Hence attempts to use the same approaches with other genetic diseases are likely to be frustrated by a lack of suitably untrammelled populations and by difficulties accounting for poorly understood genetic processes. We conclude that although this combination of molecular and population genetics is successful when applied to the study of haemoglobinopathies, it may not be so easy to apply it to the study of other genetic diseases.

Africa, Northern↗
PubMed1993

The population genetics of the haemoglobinopathies.

The haemoglobinopathies are the commonest single gene disorders known, and are so common in some regions of the world that the majority of the population carries at least one genetic abnormality affecting the structure or synthesis of the haemoglobin molecule. The prevalence of the common haemoglobinopathies (the alpha- and beta-thalassaemias, HbS, HbC and HbE) is almost certainly a result of the protection they provide against malaria, as the epidemiological evidence reviewed in this chapter shows. World-wide, the distributions of malaria and the common haemoglobinopathies largely overlap, and micro-epidemiological surveys have confirmed the close relationship between the disorders. However, there are complications to this picture which appear to undermine the malaria hypothesis. First, in some areas, malaria and haemoglobinopathies are not coincident. Second, the malaria hypothesis does not easily explain why no two regions of the world have the same haemoglobinopathy or combination of haemoglobinopathies. The majority of mutations have arisen only once and are regionally specific. By using molecular characterization of mutations and the analysis of haplotypes on haemoglobinopathy-bearing chromosomes it is possible to show how a combination of selection by malaria, genetic drift and population movements can explain the first complication. In order to explain the second, we have argued that malaria selection has operated relatively recently on human populations (within the last 5000 years). The present distribution is then seen as the result of selection elevating sporadic mutations in local populations. In the absence of sufficient gene flow to spread all mutations to all populations, the consequence is a patchwork distribution of haemoglobinopathies. Given time, we would expect the mutations that protect and do not compromise the health of their carriers to become widely disseminated, but it is likely that human intervention will alter this process of natural selection.

Africa↗
PubMed1993

A computer simulation study of VNTR population genetics: constrained recombination rules out the infinite alleles model.

Extensive allelic diversity in variable numbers of tandem repeats (VNTRs) has been discovered in the human genome. For population genetic studies of VNTRs, such as forensic applications, it is important to know whether a neutral mutation-drift balance of VNTR polymorphism can be represented by the infinite alleles model. The assumption of the infinite alleles model that each new mutant is unique is very likely to be violated by unequal sister chromatid exchange (USCE), the primary process believed to generate VNTR mutants. We show that increasing both mutation rates and misalignment constraint for intrachromosomal recombination in a computer simulation model reduces simulated VNTR diversity below the expectations of the infinite alleles model. Maximal constraint, represented as slippage of single repeats, reduces simulated VNTR diversity to levels expected from the stepwise mutation model. Although misalignment rule is the more important variable, mutation rate also has an effect. At moderate rates of USCE, simulated VNTR diversity fluctuates around infinite alleles expectation. However, if rates of USCE are high, as for hypervariable VNTRs, simulated VNTR diversity is consistently lower than predicted by the infinite alleles model. This has been observed for many VNTRs and accounted for by technical problems in distinguishing alleles of neighboring size classes. We use sampling theory to confirm the intrinsically poor fit to the infinite alleles model of both simulated VNTR diversity and observed VNTR polymorphisms sampled from two Papua New Guinean populations.

Alleles↗
PubMed1992

The evolution of tandemly repetitive DNA: recombination rules.

Variable numbers of tandem repeats (VNTRs), which include hypervariable regions, minisatellites and microsatellites, can be assigned together with satellite DNAs to define a class of noncoding tandemly repetitive DNA (TR-DNA). The evolution of TR-DNA is assumed to be driven by an unbiased recombinational process. A simulation model of unequal exchange is presented and used to investigate the evolutionary persistence of single TR-DNA lineages. Three different recombination rules are specified to govern the expansion and contraction of a TR-DNA lineage from an initial array of two repeats to, finally, a single repeat allele, which cannot participate in a misalignment and exchange process. In the absence of amplification or selection acting to bias array evolution toward expansion, the probability of attaining a target array size is a function only of the initial number of repeats. We show that the proportions of lineages attaining a targeted array size are the same irrespective of recombination rule and rate, demonstrating that our simulation model is well behaved. The time taken to attain a target array size, the persistence of the target array, and the total persistence time of repetitive array structure, are functions of the initial number of repeats, the rate of recombination, and the rules of misalignment preceding recombinational exchange. These relationships are investigated using our simulation model. While misalignment constraint is probably greatest for satellite DNA it also seems important in accounting for the evolution of VNTR loci including minisatellites. This conclusion is consistent with the observed nonrandom distributions of VNTRs and other TR-DNAs in the human genome.

Biological Evolution↗
PubMed1991

Phospholipase C-sensitive factor VII complexes in dog plasma.

We report the presence of a phospholipase c-sensitive activated factor VII complex in canine plasma after feeding a special diet. Low levels of complex was observed in the fasting state. The response to feeding in terms of activated factor VII varied markedly among the dogs investigated.

Animals↗
PubMed1989

Population bottlenecks in Polynesia revealed by minisatellites.

Tandem-repetitive highly variable loci in the human genome (minisatellites) have been used in gene mapping and as DNA "fingerprints", but they have not yet found much application in population genetics. We have investigate the capacity of six minisatellites to discriminate between four populations in Oceania. We find that in comparison to Melanesians, Polynesians have a significant loss of heterozygosity (or gene diversity), not noted using more traditional markers. We show also that the number of alleles, the allele distribution and the mutation rates at the Polynesian minisatellite loci do not deviate from those predicted by the neutral mutation/infinite allele model. The low gene diversity is therefore likely to be a result of the maintenance of small population sizes and bottleneck effects during the colonization of the Pacific.

Alleles↗
PubMed1986

Comparison of the alpha-adrenoceptor characteristics in human and canine prostate.

Alpha adrenoceptors, mediating contraction, have been shown to be present in strips of hypertrophic prostate surgically removed from patients with benign prostatic hypertrophy (BPH), providing a rational explanation for the demonstrated effectiveness of alpha antagonists in the symptomatic treatment of this disease. Inasmuch as the dog develops spontaneous and hormonally induced prostatic enlargement, studies were performed to compare the adrenoceptor characteristics of canine and human prostate to determine whether the dog represents a useful model to search for more effective alpha-adrenolytic therapy for human BPH. Norepinephrine produces contraction in isolated strips of canine prostate although it is only one-tenth as potent as previously reported in human tissue. In contrast, several selective alpha 1-adrenoceptor agonists are potent contractile agents in canine prostate, but are nearly inactive in the human tissue. This difference may be a consequence of their partial agonist character. The potency of selective alpha-adrenoceptor antagonists in blocking the norepinephrine-induced contractile response in both canine and human tissue is consistent with an action of norepinephrine on the alpha 1 adrenoceptor. The receptor dissociation constants for these antagonists are similar in prostatic tissue from dogs and humans, and the values in canine tissue correlate well with those obtained in the rabbit ear artery, a standard model for vascular alpha 1 adrenoceptors. Hence the dog may represent a useful model for studies of the potential responsiveness of human prostate to adrenergic agents.

Adrenergic alpha-Antagonists↗
PubMed1985

Population structure in the Connecticut Valley: II. A comparison of multidimensional scaling solutions of migration matrices and isonymy.

In a previous paper (Swedlund et al., 1984) we have described the population structure of the historical Connecticut River Valley of Massachusetts in terms of matrimonial migration matrices. Using procedures described by Morton (1973), Harpending and Jenkins (1974), Jorde (1980), and others the exchanges between subdivisions which make up the matrices are made column stochastic and analyzed to predict genetic kinship. Subsequently the kinship estimates within and between subdivisions can be interpreted as genetic covariance and compared to the actual geographic distances between the respective subdivisions using a principal components analysis. In the present paper we extend these results by applying nonmetric multidimensional scaling to the migration matrices, and to isonymy matrices based on the same communities. We demonstrate that the multidimensional scaling configurations of marital migration represent the actual geographic relationships between the communities quite effectively for this particular case study from historical Massachusetts. Moreover, we argue that while these migration data may provide good estimates of social and genetic exchange between the subdivisions, surname analysis may also be informative of processes not revealed in the migration matrices alone.

Demography↗