Biomedical subjects
Publications and source records attributed to T Foote.
Comparative genome analysis enables the sites of centromeres, telomeres and nucleolar organiser regions to be aligned with borders that define the sets of linked genes conserved across the cereal genomes. This provides a basis for studying cereal genome evolution.
Detailed physical mapping of markers from rice chromosome 9, and from syntenous (at the genetic level) regions of other cereal genomes, has resulted in rice yeast artificial chromosome (YAC) contigs spanning parts of rice 9. This physical mapping, together with comparative genetic mapping, has demonstrated that synteny has been largely maintained between the genomes of several cereals at the level of contiged YACs. Markers located in one region of rice chromosome 9 encompassed by the YAC contigs have exhibited restriction fragment length polymorphism (RFLP) using deletion lines for the Ph1 locus. This has allowed demarcation of the region of rice chromosome 9 syntenous with the ph1b and ph1c deletions in wheat chromosome 5B. A group of probes located in wheat homoeologous group 5 and barley chromosome 5H, however, have synteny with rice chromosomes other than 9. This suggests that the usefulness of comparative trait analysis and of the rice genome as a tool to facilitate gene isolation will differ from one region to the next, and implies that the rice genome is more ancestral in structure than those of the Triticeae.
Comparative genomics reveals that cereal genomes are composed of similar genomic building blocks (linkage blocks). By stacking these blocks in a unique order, it is possible to construct a single ancestral 'chromosome' which can be cleaved to give the basic structure of the 56 different chromosomes found in wheat, rice, maize, sorghum, millet and sugarcane. The borders of linkage blocks are defined by cereal centromeric and telomeric sites. However, a number of studies have shown that telomeric heterochromatin has neocentromeric activity, implying that linkage blocks are in fact defined by centromeric-like sites with conserved sequences. The structure of the ancestral cereal genome thus resembles a holocentric chromosome, which is the chromosome structure shared by the closest relatives of the Gramineae, the Cypericeae and Juncaceae.
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There is both clinical and histopathologic evidence for peripheral visual field loss and optic nerve degeneration in longstanding papilledema due to idiopathic intracranial hypertension (IIH). The purpose of this study was to look at the extent and distribution of axonal dropout in secondary optic atrophy due to IIH. Both optic nerves from a 29-year-old man with a two year history of IIH were examined histologically and morphometrically. A high-contrast lipid (myelin) stain, paraphenylenediamine (PPD), and a semiautomated image analysis system were employed to resolve sufficiently the optic nerve fiber images for counts and for measurement. There were 80% and 90% losses of axons, respectively, in the right and left optic nerves consequent to IIH. The axonal loss in the peripheral area of each optic nerve was much more severe than that in inner sectors (= 0.001 for the right optic nerve and = 0.005 for the left). This pattern of axonal dropout is consistent with the preservation of good central visual acuity despite devastating optic nerve atrophy, and with the severe peripheral visual field loss noted in this patient.
In order to further study AIDS (acquired immunodeficiency syndrome) related neuropathologic findings, specifically progressive diffuse leuko-encephalopathy (PDL) and optic neuropathy, ten macaque monkeys (Macaca mulatta) were infected with simian immunodeficiency virus (SIV), observed for varying periods, and then sacrificed and tissue prepared for analysis. A marked difference from human AIDS pathology was found: in all monkeys, there was significant peripheral axonal dropout, as opposed to relatively little dropout in the central areas of the nerves (t stat. = -5.9, p < .001). In those monkeys infected with SIV for over one year, the axonal loss in the periphery was also greater than in the central optic nerve (t stat. = -5.03, p < .001); monkeys infected with SIV for less than one year had slightly less peripheral than central loss (t stat. = -4.5, p = .001). When compared with humans, however, it was found that the overall loss of axons was less (15% in monkeys vs. up to 45% in humans). There was also a lack of discernible retinal pathology, such as cotton wool spots, in the monkey tissue.
Unlike mammalian genomes, cereal (Gramineae) genomes exhibit little suppression of CpG dinucleotides. In cereal genomes, however, most of the numerous potential recognition sites for CpG methylation-sensitive restriction enzymes are methylated. Analysis of cereal genomic libraries and of regions flanking genes indicates that unmethylated NotI sites are useful landmarks for regions containing genes/single-copy sequences. Studies of a rye chromosome arm indicate that its pericentromeric region has a reduced density of unmethylated NotI (and MluI) sites and therefore of genes. Unmethylated MluI and NruI sites are distributed nonrandomly in the genomes of wheat, barley, and rice. Analysis of the genomic blocks defined by these sites in wheat and barley indicates that they are most likely to have arisen by amplification. These observations form the basis of a proposed model for the organization and evolution of the wheat, barley, and rice genomes.
We describe here a protocol for obtaining clones containing sequences present in low copy-number from genomic DNA where moderately and highly repeated sequences predominate. Specific chromosomal regions can be targeted by using deletion or addition line material. We have used this protocol to identify a sequence which has been deleted in both the tetraploid and hexaploid wheat mutants for the homoeologous chromosome pairing locus.
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