PubMed Health⌕ Search

Biomedical subjects

Michael D Wilson

Publications and source records attributed to Michael D Wilson.

7 recordsLinked to original sources

Investigating Environmental Determinants of Hookworm Transmission using GPS Tracking and Metagenomics Technologies.

To identify potential sources of hookworm infections in a Ghanaian community of endemicity that could be targeted to interrupt transmission, we tracked the movements of infected and noninfected persons to their most frequented locations. Fifty-nine participants (29 hookworm positives and 30 negatives) wore GPS trackers for 10 consecutive days. Their movement data were captured in real time and overlaid on a community grid map. Soil samples were collected and divided into two parts: one for determining the physical and chemical properties and the other for culture of helminth larvae. Soil parameters were determined using standard methods, and the number of larvae recovered from Baermann cultures (expressed as larvae per gram of soil) was recorded. We found no significant difference in the larval counts between sites of infected and noninfected participants (P = 0.59). Sandy-loam soil, pH, and effective cation exchange capacity were associated with high larval recovery counts (P <0.001), whereas nitrogen and clay content were associated with low counts (P <0.001). Genomic DNA was extracted from helminth larvae, and species were identified using metagenomic analysis of DNA sequences. The dominant helminth species identified were Panagrolaimus superbus, Parastrongyloides trichosuri, Trichuris trichiura (human whipworm), and Ancylostoma caninum (dog hookworm). Despite Necator americanus being the predominant species in the community, no larvae of this species were identified. This study, however, demonstrates the feasibility of applying molecular tools for identifying environmental factors and places associated with exposure to human and zoonotic helminths, including areas that may be targeted to break transmission in communities where infection is endemic.

Humans↗

Analysis of the conservation of synteny between Fugu and human chromosome 12.

BACKGROUND: The pufferfish Fugu rubripes (Fugu) with its compact genome is increasingly recognized as an important vertebrate model for comparative genomic studies. In particular, large regions of conserved synteny between human and Fugu genomes indicate its utility to identify disease-causing genes. The human chromosome 12p12 is frequently deleted in various hematological malignancies and solid tumors, but the actual tumor suppressor gene remains unidentified. RESULTS: We investigated approximately 200 kb of the genomic region surrounding the ETV6 locus in Fugu (fETV6) in order to find conserved functional features, such as genes or regulatory regions, that could give insight into the nature of the genes targeted by deletions in human cancer cells. Seven genes were identified near the fETV6 locus. We found that the synteny with human chromosome 12 was conserved, but extensive genomic rearrangements occurred between the Fugu and human ETV6 loci. CONCLUSION: This comparative analysis led to the identification of previously uncharacterized genes in the human genome and some potentially important regulatory sequences as well. This is a good indication that the analysis of the compact Fugu genome will be valuable to identify functional features that have been conserved throughout the evolution of vertebrates.

Animals↗

Recent segmental and gene duplications in the mouse genome.

BACKGROUND: The high quality of the mouse genome draft sequence and its associated annotations are an invaluable biological resource. Identifying recent duplications in the mouse genome, especially in regions containing genes, may highlight important events in recent murine evolution. In addition, detecting recent sequence duplications can reveal potentially problematic regions of the genome assembly. We use BLAST-based computational heuristics to identify large (>/= 5 kb) and recent (>/= 90% sequence identity) segmental duplications in the mouse genome sequence. Here we present a database of recently duplicated regions of the mouse genome found in the mouse genome sequencing consortium (MGSC) February 2002 and February 2003 assemblies. RESULTS: We determined that 33.6 Mb of 2,695 Mb (1.2%) of sequence from the February 2003 mouse genome sequence assembly is involved in recent segmental duplications, which is less than that observed in the human genome (around 3.5-5%). From this dataset, 8.9 Mb (26%) of the duplication content consisted of 'unmapped' chromosome sequence. Moreover, we suspect that an additional 18.5 Mb of sequence is involved in duplication artifacts arising from sequence misassignment errors in this genome assembly. By searching for genes that are located within these regions, we identified 675 genes that mapped to duplicated regions of the mouse genome. Sixteen of these genes appear to have been duplicated independently in the human genome. From our dataset we further characterized a 42 kb recent segmental duplication of Mater, a maternal-effect gene essential for embryogenesis in mice. CONCLUSION: Our results provide an initial analysis of the recently duplicated sequence and gene content of the mouse genome. Many of these duplicated loci, as well as regions identified to be involved in potential sequence misassignment errors, will require further mapping and sequencing to achieve accuracy. A Genome Browser database was set up to display the identified duplication content presented in this work. This data will also be relevant to the growing number of investigators who use the draft genome sequence for experimental design and analysis.

Animals↗

Human chromosome 7: DNA sequence and biology.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.

Animals↗

Characterization of the murine hyaluronidase gene region reveals complex organization and cotranscription of Hyal1 with downstream genes, Fus2 and Hyal3.

Hyaluronidases are required for the breakdown of hyaluronan (HA), an abundant component of the extracellular matrix of vertebrate tissues. Multiple hyaluronidase genes have been identified, but the only clue to the function of their products has come from the identification of hyaluronidase 1 deficiency in a single patient with a mild clinical phenotype. As a first step in the generation of mice with hyaluronidase deficiency, we have used experimental and bioinformatic approaches to examine the organization of the mouse chromosome 9 region containing, in order, Hyal2, Hyal1, and Hyal3. This region was found to be complex, with Fus2 partially embedded in Hyal3, and Ifrd2 immediately downstream from Hyal3. The Hyal genes were all found to have four exons, and exons 2-4 exhibited the highest sequence conservation. Northern blot analysis demonstrated that the tissue expression profile for Hyal1 was similar in mice and humans, but a greater number of transcripts was detected in mouse tissues. Hyal3 was expressed more broadly in mice compared with humans and again exhibited additional transcripts. Reverse transcription-PCR demonstrated that some of the larger Hyal1 transcripts, seen on the Northern blot, were the result of cotranscription of Hyal1 with downstream genes, Fus2 or Hyal3. In vitro transcription/translation of one of the high abundance bicistronic transcripts produced Hyal 1, suggesting that Hyal 1 could be produced from all of the bicistronic transcripts. Characterization of the region including mouse Hyal1 and Hyal3 revealed complex organization and transcription that must be considered in the development and interpretation of mouse models involving genes in this region.

Amino Acid Sequence↗

Corneal shape in hyperopia.

Background: A trend towards decreased peripheral corneal flattening with increasing myopia has recently been demonstrated. The present study was conducted to determine whether corneal asphericity also varies significantly with hyperopic refractive error. Methods: Thirty-five eyes with spherical equivalent refractive error ranging from -0.37 D to +6.00 D were examined. A conicoid equation was fitted to videokeratoscopic (Topographic Modeling System) data and corneal asphericity and apical radius of curvature values were calculated for each subject. Axial length measurements were made using a hand-held biometric ruler. Keratometry was also performed on each eye. Results: The relationship between corneal asphericity (Q) and spherical equivalent refractive error was not statistically significant (p = 0.7419). In addition, no association could be demonstrated between Q and corneal radius of curvature or between Q and axial length. Corneal radius of curvature was positively correlated with axial length (r = 0.367, p = 0.0298). Axial length was found to decrease as hyperopic refractive error increased (r = 0.753, p = 0.0001). Conclusions: For hyperopic eyes, corneal asphericity does not appear to be significantly correlated with refractive error, a finding that is at variance with previous data for myopic eyes showing an association between these two variables. The results suggest that there may be differences between hyperopic and myopic eyes with regard to the anterior segment changes that occur during refractive error development.

Journal Article↗