Biomedical subjects

Alan M Durham

Publications and source records attributed to Alan M Durham.

7 recordsLinked to original sources

PubMed2006

Extense variant gene family repertoire overlap in Western Amazon Plasmodium falciparum isolates.

In order to find a molecular basis for observations of relatively fast developing immunity to malarial infections in the Western Amazon region, the partial var, stevor and rif gene repertoires of nine different Plasmodium falciparum isolates collected in 1985 and 2000-2004 were evaluated. In contrast to previous results from South East Asia, the variant gene repertoire in Brazilian isolates is rather small and redundant. While the individual var repertoire sizes of Brazilian strains did not differ from Southeast Asian/African isolates, we found an over three times higher overlap of var sequence repertoires in Amazonian strains which was also conserved over time, suggesting the ongoing circulation of a similar var gene repertoire. Coincidently, almost 40% of the sequences identified herein showed the highest degree of similarity to var genes from either Brazilian or Venezuelan isolates, indicating a limited var repertoire of P. falciparum in the Amazon Basin as a whole. The intrastrain similarities of var genes were slightly but significantly lower than in Southeast Asian/African samples suggesting a higher selective pressure for diversification in Amazonian isolates. Despite of higher copy numbers per genome, rif genes also showed a significant repertoire overlap. stevor genes, which share the same predominant subtelomeric localization as var and rif genes, showed a still higher repertoire overlap and were highly similar to 3D7 stevor genes, indicating stronger functional conservation than var and rif genes. This is the first study that reveals that P. falciparum variant gene repertoires of certain areas can be limited. This has important implications for the strain-specific immunity against variant antigens occurring in these areas.

Animals↗

PubMed2006

Multi-character population study of the vir subtelomeric multigene superfamily of Plasmodium vivax, a major human malaria parasite.

Plasmodium vivax, the most widely distributed human malaria parasite, contains the subtelomeric multigene vir superfamily corresponding to circa 10% of its coding genome. In this work, we used a multi-character strategy to study the vir gene repertoire circulating in natural parasite populations obtained directly from 32 human patients from endemic regions of Brazil and Sri Lanka. Cladistic analysis confirmed the existence of vir subfamilies, which varied in size and allele polymorphisms. Moreover, different motifs, protein domain, and secondary structures were predicted for each subfamily. Of importance, not all vir sequences possess a recognizable Pexel motif recently shown to be important, though not essential, signal for transportation to the cell membrane of infected red blood cells. Furthermore, subfamilies A and D display common structural features with the recently described P. falciparum SURFIN and Pfmc-2tm subtelomeric multigene families. These results suggest that VIR proteins can have different subcellular localizations and functions. This is the first study on a population level of the P. vivax vir subtelomeric multigene superfamily.

Amino Acid Motifs↗

PubMed2006

Origins of sequence diversity in the malaria vaccine candidate merozoite surface protein-2 (MSP-2) in Amazonian isolates of Plasmodium falciparum.

The recent evolution of Plasmodium falciparum is at odds with the extensive polymorphism found in most genes coding for antigens. Here, we examined the patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2), a major malarial repetitive surface antigen. We compared the msp-2 gene sequences from closely related clones derived from sympatric parasite isolates from Brazilian Amazonia and used microsatellite typing to examine, in these same clones, the haplotype background of chromosome 2, where msp-2 is located. We found examples of msp-2 sequence rearrangements putatively created by nonreciprocal recombinational events, such as replication slippage and gene conversion, while maintaining the chromosome haplotype. We conclude that these nonreciprocal recombination events may represent a major source of antigenic diversity in MSP-2 in P. falciparum populations with low rates of classical meiotic recombination.

Alleles↗

PubMed2005

TRAP: automated classification, quantification and annotation of tandemly repeated sequences.

TRAP, the Tandem Repeats Analysis Program, is a Perl program that provides a unified set of analyses for the selection, classification, quantification and automated annotation of tandemly repeated sequences. TRAP uses the results of the Tandem Repeats Finder program to perform a global analysis of the satellite content of DNA sequences, permitting researchers to easily assess the tandem repeat content for both individual sequences and whole genomes. The results can be generated in convenient formats such as HTML and comma-separated values. TRAP can also be used to automatically generate annotation data in the format of feature table and GFF files.

Algorithms↗

PubMed2005

EGene: a configurable pipeline generation system for automated sequence analysis.

UNLABELLED: EGene is a generic, flexible and modular pipeline generation system that makes pipeline construction a modular job. EGene allows for third-party programs to be used and integrated according to the needs of distinct projects and without any previous programming or formal language experience being required. EGene comes with CoEd, a visual tool to facilitate pipeline construction and documentation. A series of components to build pipelines for sequence processing is provided. AVAILABILITY: http://www.lbm.fmvz.usp.br/egene/ CONTACT: alan@ime.usp.br; argruber@usp.br SUPPLEMENTARY INFORMATION: http://www.lbm.fmvz.usp.br/egene/

Chromosome Mapping↗

PubMed2004

Characterization of SCAR markers of Eimeria spp. of domestic fowl and construction of a public relational database (The Eimeria SCARdb).

This study reports the development and characterization of 151 sequence characterized amplified region (SCAR) markers for the seven Eimeria species that infect the domestic fowl. From this set, 84 markers are species-specific and 67 present partial specificity. The complete nucleotide sequence was derived for all markers, revealing the presence of micro- and minisatellite repetitive units in 22 SCARs, with up to five distinct repeat units being observed per marker. Only 15 markers showed significant hits in similarity searches against public sequence databases, thus confirming their anonymous and non-coding character. Finally, a relational database of the markers (the Eimeria SCARdb) was developed and made available on the Internet, providing a valuable resource of SCAR markers that can be useful for molecular diagnosis, and also for epizootiological, genetic variability and genome mapping studies.

Animals↗

PubMed2004

DNA microarray-based genome comparison of a pathogenic and a nonpathogenic strain of Xylella fastidiosa delineates genes important for bacterial virulence.

Xylella fastidiosa is a phytopathogenic bacterium that causes serious diseases in a wide range of economically important crops. Despite extensive comparative analyses of genome sequences of Xylella pathogenic strains from different plant hosts, nonpathogenic strains have not been studied. In this report, we show that X. fastidiosa strain J1a12, associated with citrus variegated chlorosis (CVC), is nonpathogenic when injected into citrus and tobacco plants. Furthermore, a DNA microarray-based comparison of J1a12 with 9a5c, a CVC strain that is highly pathogenic and had its genome completely sequenced, revealed that 14 coding sequences of strain 9a5c are absent or highly divergent in strain J1a12. Among them, we found an arginase and a fimbrial adhesin precursor of type III pilus, which were confirmed to be absent in the nonpathogenic strain by PCR and DNA sequencing. The absence of arginase can be correlated to the inability of J1a12 to multiply in host plants. This enzyme has been recently shown to act as a bacterial survival mechanism by down-regulating host nitric oxide production. The lack of the adhesin precursor gene is in accordance with the less aggregated phenotype observed for J1a12 cells growing in vitro. Thus, the absence of both genes can be associated with the failure of the J1a12 strain to establish and spread in citrus and tobacco plants. These results provide the first detailed comparison between a nonpathogenic strain and a pathogenic strain of X. fastidiosa, constituting an important step towards understanding the molecular basis of the disease.

Adhesins, Bacterial↗