Biomedical subjects

R M Badge

Publications and source records attributed to R M Badge.

5 recordsLinked to original sources

PubMed2001

Sox8 gene expression identifies immature glial cells in developing cerebellum and cerebellar tumours.

Sox8 is a member of the E subgroup of Sox genes, the other members of which are Sox9 and Sox10, both of which are implicated in specific human disorders. Recently, Sox8 homologues have been cloned in chick, mouse and human and have been shown to be strongly expressed in the embryonic and adult brain. Nevertheless, the cell types that express Sox8 have not been determined. We show here that Sox8 is expressed in immature glia in the developing cerebellum. Sox8 is also expressed in scattered cells in the cerebellar tumour, medulloblastoma. This gene therefore provides an early glial marker that may provide more detailed insight into the cellular makeup and consequent behaviour of medulloblastomas.

Animals↗

PubMed2000

Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination.

Segregation analysis of CEPH and other pedigrees yielded six paternal crossover breakpoints in the approximately 85 kb interval between the minisatellite loci D16S309 (MS205) and D16S83 (EKMDA2) in 16p13.3. Three crossovers were mapped to within the same small (<3 kb) interval, which does not co-localize with any tandem repeat array or expressed sequence. Haplotyping of loci harbouring single nucleotide polymorphism (SNP) markers in this interval confirmed the exchange of flanking markers in the three recombinant individuals. Sequence analysis revealed the presence of recombination-associated motifs and binding sites for the protein translin. Haplotyping of 108 individuals from three European populations at four loci harbouring SNPs showed substantial linkage equilibrium across this interval. Hence molecular and population genetic data are consistent with the presence of an intense male-specific recombination hotspot at this locus.

Chromosome Mapping↗

PubMed1998

A novel repressor of P element transposition in Drosophila melanogaster.

We have discovered, in an inbred line (Loua) of Drosophila melanogaster from Zaire, a third chromosome showing unusual P element repression. Repression of P element transposition by this chromosome, named Loua3, is dominant zygotic and has three unusual properties. Firstly, its repression of the gonadal dysgenesis caused by a strong P haplotype is strongly temperature-dependent, being most evident at higher rearing temperatures. Secondly, subdivision of Loua3 by recombination abolishes repression: the effect is apparently a function of the intact chromosome. Finally, Loua3 also diminishes somatic lethality when chromosomes carrying many 'ammunition' elements (Birmingham2) are exposed to the constitutive transposase source delta 2-3(99B). The chromosome has 17 P elements, none full-length, located in at least 12 dispersed positions.

Animals↗

PubMed1997

The role of host factors in the population dynamics of selfish transposable elements.

Previous models of the evolution of selfish transposable genetic elements have failed to include the possibility that transposition may be limited by shortage of a host-encoded factor. The titration of host factors may be important in limiting the rate of transpositional increase in these elements. This will be exacerbated if multiple copies of the host factor protein must bind simultaneously to the target element. In the case of the Drosophila melanogaster P transposable element, which can exist as autonomous and as non-autonomous copies, there is evidence that a host-encoded protein, IRBP, is required for the transposition process. We have produced a specific model of the invasion of a host population by the P element, in which we have incorporated the requirement for the multiple binding of a host factor. We find that, for the P family, in which it is apparently transposition itself that creates selective harm to the host, the effect of selection in the context of host factor limitation is to drive up copy number. This can result in a novel high copy number-low transposition state. We also find that host factor limitation reinforces the tendency for transposable elements that create sterility to be replaced by their deletion derivatives.

Animals↗

PubMed1997

Population genetics models of transposable elements.

The control of transposable element copy number is of considerable theoretical and empirical interest. Under simple models, copy numbers may increase without limit. Mechanisms that can prevent such an increase include those in which the effect of selection increases with copy number, those in which the rate of transposition decreases with copy number, and those where unlimited increase in copy number is prevented by the consequences of functional heterogeneity in the transposable element family. Finite population sizes may attenuate the power of natural selection to act on transposable element copy number in a number of ways that may be of particular importance in laboratory populations. First, a small host population size will create occasional periods in which the variance between individuals in copy number is diminished, and with it the power of natural selection, even when the expected variance is Poisson. Second, small population sizes will produce high-frequency transposable element sites, systematically reducing the variance in copy number. The consequences will be particularly profound when the selective damage of transposable elements follows from their heterozygosity, as when ectopic exchange limits copy number.

Animals↗