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Kevin Tang

Publications and source records attributed to Kevin Tang.

3 recordsLinked to original sources

GeneChip resequencing of the smallpox virus genome can identify novel strains: a biodefense application.

We developed a set of seven resequencing GeneChips, based on the complete genome sequences of 24 strains of smallpox virus (variola virus), for rapid characterization of this human-pathogenic virus. Each GeneChip was designed to analyze a divergent segment of approximately 30,000 bases of the smallpox virus genome. This study includes the hybridization results of 14 smallpox virus strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence information included in the design of the smallpox virus resequencing GeneChips; similar information for the remaining strains was not tiled as a reference in these GeneChips. By use of variola virus-specific primers and long-range PCR, 22 overlapping amplicons were amplified to cover nearly the complete genome and hybridized with the smallpox virus resequencing GeneChip set. These GeneChips were successful in generating nucleotide sequences for all 14 of the smallpox virus strains hybridized. Analysis of the data indicated that the GeneChip resequencing by hybridization was fast and reproducible and that the smallpox virus resequencing GeneChips could differentiate the 14 smallpox virus strains characterized. This study also suggests that high-density resequencing GeneChips have potential biodefense applications and may be used as an alternate tool for rapid identification of smallpox virus in the future.

Bioterrorism↗

Screening for HFE and iron overload.

Type 1 hereditary hemochromatosis is a common disorder of iron overload occurring in individuals homozygous for the C282Y HFE gene mutation. It can be a progressive and fatal condition. Early detection and phlebotomy prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with clinical features suggestive of iron loading. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified. Potential ethical, legal, and psychosocial issues arising through application of genetic screening programs also must be resolved prior to implementation of general population screening programs.

Genetic Markers↗

New perspectives on rickettsial evolution from new genome sequences of rickettsia, particularly R. canadensis, and Orientia tsutsugamushi.

The complete genome sequences available for eight species of Rickettsia and information for other near relatives in the Rickettsiales including Orientia and species of Anaplasmataceae are a rich resource for comparative analyses of the evolution of these obligate intracellular bacteria. Differences in these organisms have permitted them to colonize varied intracellular compartments, arthropod vectors, and vertebrate reservoirs in both pathogenic and symbiotic relationships. We summarize some comparative aspects of the genomes of these organisms, paying particular attention to the recently completed sequence for R. canadensis McKiel strain and an estimated two-thirds of the genome sequence for a Thailand patient isolate of Orientia tsutsugamushi. The Rickettsia genomes exhibit a high degree of synteny punctuated by distinctive chromosome inversions and consistent phylogenetic relationships regardless of whether protein coding sequences or RNA genes, concatenated open reading frames or gene regions, or whole genomes are used to construct phylogenetic trees. The aggregate characteristics (number, length, composition, repeat identity) of tandem repeat sequences of Rickettsia, which often exhibit recent and rapid divergence between closely related strains and species of bacteria, are also very conserved in Rickettsia but differed significantly in Orientia. O. tsutsugamushi shared no significant synteny to species of Rickettsia or Anaplasmataceae, supporting its placement in a unique genus. Like Rickettsia felis, Orientia has many transposases and ankyrin and tetratricopeptide repeat domains. Orientia shares the important ATP/ADP translocase and proline-betaine transporter multigene families with Rickettsia, but has more gene families that may be involved in regulatory and transporter responses to environmental stimuli.

Animals↗