Biomedical subjects
Publications and source records attributed to J A Donald.
Families segregating for PEPD were investigated for linkage between PEPD and APOC2. The results provide evidence for close linkage between PEPD and APOC2 in males.
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We report the isolation of a genomic clone containing the apolipoprotein CII (apo CII) gene and 5' and 3' flanking sequences. A detailed restriction map of the gene has been constructed and DNA fragments that are unique, or low copy number sequences in the genome have been identified. One of these detects a common restriction fragment length polymorphism (RFLP) with the enzyme BglI. Marked linkage disequilibrium is observed between this RFLP and that detected with the apo CII cDNA clone, even though the two variable restriction enzyme sites are approximately 12kb apart. However, the usefulness of the apo CII gene as a marker for linkage studies is increased by the use of both RFLPs.
We have used DNA and protein polymorphisms for the third complement component (C3) to assess the potential of DNA markers in the diagnosis and study of familial hypercholesterolaemia (FH), and to confirm the reported linkage between FH and C3. The inheritance of FH and the C3 gene has been studied in 10 families by combining information from both the protein and DNA polymorphisms. Our results confirm that the C3 gene is loosely linked to the gene causing FH (lod score maximum of 2.0) at a recombination distance of 0.15. When these results are combined with previously published data the overall lod score maximum is 4.75 at a recombination distance of 0.2, meaning that the two genes will be inherited together in only about 80% of children. These results confirm that the gene that causes familial hypercholesterolaemia is linked to C3 and is therefore on chromosome 19, but C3 is not close enough to be used as a diagnostic marker.
Haplotypes have been determined for alleles at two separate polymorphic sites within the human structural gene for complement component 3, identified as a protein polymorphism and as a restriction fragment length polymorphism by hybridization using a cloned gene probe. No evidence was found for appreciable disequilibrium between alleles at these sites, despite their very close linkage.
A number of somatic cell hybrids between red kangaroo (Macropus rufus) and mouse cells, which lose marsupial chromosomes, were found to express the kangaroo form of LDH-A. Concordance between the expression of marsupial LDH-A and the presence of chromosome 5 in the hybrid cells and selected subclones enabled the gene for LDH-A to be assigned to this chromosome. This is the first autosomal gene assignment in a marsupial and should prove important for chromosome mapping in the red kangaroo and in many other species of marsupials.
A series of marsupial-eutherian somatic cell hybrids was produced by fusion between lymphocytes from the red kangaroo (Macropus rufus) and HPRT-deficient mouse cells. The hybrids lost marsupial chromosomes and could therefore be used to map marsupial genes. Several of the hybrids contained a complete red kangaroo X chromosome and expressed the kangaroo form of the enzymes HPRT, G6PD, and PGKA. A number of HPRT-deficient revertant cell lines were derived from the hybrids. These possessed a variety of partially deleted X chromosomes. With these cell lines, it has been possible to establish the X-linkage of the genes for HPRT, G6PD, and PGKA in this marsupial and to localize these three genes to the terminal portion of the euchromatic arm of the red kangaroo X chromosome.
The paternal X inactivation system of kangaroos has been investigated in this study by using tritiated uridine-induced chromosome aberrations to distinguish the active from the inactive X. Previous work in eutherian mammals has demonstrated that constitutive heterochromatic chromosome regions are less susceptible to breakage by tritiated uridine than euchromatic regions. The results of a comparison between the paternal X chromosome of a wallaroo X red kangaroo hybrid female and the two X chromosomes of a red kangaroo female suggested that the facultative heterochromatin of the X is also less susceptible to breakage by this treatment. However there were significantly more breaks of the paternal X in fibroblasts than in lymphocytes of the hybrid female, which agrees with biochemical findings suggesting activation of the paternal X in fibroblasts. Our results strengthen the suggestion of other workers that the reduced number of aberrations in heterochromatin occurs because such breaks occur principally when the DNA and labelled RNA are in apposition during transcription. Some evidence was found of an apparent toxicity effect of the tritiated uridine solution on the cells.