Biomedical subjects
Publications and source records attributed to S K Heath.
Prenatal diagnosis was performed by both DNA and enzymatic analysis on non-identical twins conceived by in vitro fertilization and at risk of succinate semialdehyde dehydrogenase deficiency. One fetus was predicted to be affected and one unaffected and selective fetal reduction was performed.
This study reports the development of a mutation screening strategy for tyrosinaemia type I, and the identification of six novel mutations in the FAA gene.
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We have isolated and characterized a novel PHD finger gene, PHF2, which maps to human Chromosome (Chr) 9q22 close to D9S196. Its mouse homolog was also characterized and mapped to the syntenic region on mouse Chr 13. The predicted human and mouse proteins are 98% identical and contain a PHD finger domain, eight possible nuclear localization signals, two potential PEST sequences, and a novel conserved hydrophobic domain. Northern analysis shows widespread expression of PHF2 in adult tissues, while in situ hybridization on mouse embryos reveals staining in the neural tube and dorsal root ganglia significantly above a ubiquitous low level expression signal. From its expression pattern and its chromosomal localization, PHF2 is a candidate gene for hereditary sensory neuropathy type I, HSN1.
The human ninjurin gene was isolated from a cDNA library enriched for transcripts from band 9q22. A 1.2-kb message was detected for ninjurin in all human tissues studied. The full-length sequence codes for a putative 152-amino-acid protein with 89% identity to the rat ninjurin protein. The mouse homologue was isolated and showed 98% amino acid identity to the rat protein. Mapping by FISH localized mouse ninjurin to mouse chromosome 13, a region that shows synteny with human chromosome 9q22. Genomic characterization of the human gene revealed four exons covering less than 10 kb. The map position of the human gene is between the genetic markers D9S196 and D9S197 on human chromosome band 9q22. This places the gene within the candidate regions for the degenerative neurological disorder hereditary sensory neuropathy type I and the cancer predisposition syndrome multiple self-healing squamous epitheliomata.
We examined the expression of the murine homologue of myotonic dystrophy associated homeodomain protein (mDMAHP) using two different strategies. The first approach, RT-PCR, detected spliced transcripts in a wide range of embryonic and adult tissues, in a pattern overlapping substantially with the expression of mDMPK. A second approach, the generation of transgenic mice expressing the lacZ reporter gene from a 4.3 kb promoter fragment, also demonstrated expression in a range of tissues with potential links to the phenotype in myotonic dystrophy. We conclude that murine DMAHP has a similar pattern of expression to human DMAHP and will serve as a useful model for functional studies of this gene, although species differences, such as the reduced CpG island (1.8 kb compared with 3.5 kb) must be carefully considered.
There is concern that air pollution may be causing increases in asthma morbidity and mortality, especially among African-Americans. It is possible that there may be ethnic differences in susceptibility. To evaluate this speculation, a comparative pilot study of respiratory function in 10 African American and 12 Caucasian methacholine positive asthmatic males was conducted. Subjects were exposed to pure air or 1 ppm SO2 while breathing inside a polycarbonate head dome, for 10 min of rest and 10 min of exercise. Baseline and postexposure pulmonary function measurements were recorded, and nasal lavage fluid samples were collected and processed for epithelial and white blood counts. Although significant increases were seen in total respiratory resistance following SO2 exposure in both groups (P = 0.04), no ethic-based difference in response was seen. No significant differences were found in pulmonary or nasal measurements after exposure to SO2 between African-American and Caucasian subjects. No significant changes in epithelial or white blood cell count were found either when data were analyzed from the entire group or separately from the two subject groups. Even though there were no significant group changes, some individuals were particularly responsive to SO2. Three Caucasian and 5 African-American subjects showed greater than 20% increases in total respiratory resistance.