Search PubMed⌕ Search

Biomedical subjects

R G Snell

Publications and source records attributed to R G Snell.

29 records · Page 2Linked to original sources
PubMed1993

Identification of an expanded CAG repeat in the Huntington's disease gene (IT15) in a family reported to have benign hereditary chorea.

Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by the onset of non-progressive chorea in childhood and the absence of cognitive impairment. Using primers flanking the (CAG)n repeat in IT15, expansion of which is associated with HD, we have detected an abnormal PCR product in four affected members from one family where affected subjects were originally reported to have BHC. The expanded allele contains 38 repeats in the affected parent and this undergoes further enlargement to 39 and 45 repeats in the two affected offspring. We conclude that the diagnostic criteria for BHC should include a normal result from analysis for the (CAG)n expansion identified in HD.

Adult↗
PubMed1992

Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification.

We have applied the technique of exon amplification to the isolation of genes from the chromosome 4p16.3 Huntington's disease (HD) candidate region. Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs. The alpha-adducin gene maps immediately telomeric to D4S95, in a region likely to contain the HD defect, and must be scrutinized to establish whether it is the site of the HD mutation.

Alternative Splicing↗
PubMed1992

A recombination event that redefines the Huntington disease region.

We report both a recombination event that places the Huntington disease gene proximal to the marker D4S98 and an extended linkage-disequilibrium study that uses this marker and confirms the existence of disequilibrium between it and the HD locus. We also report the cloning of other sequences in the region around D4S98, including a new polymorphic marker R10 and conserved sequences that identify a gene in the region of interest.

Chromosomes, Human, Pair 4↗
PubMed1991

Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.

DNA samples were obtained from children with Wolf-Hirschhorn syndrome and their parents to assist with gene mapping studies of 4p16.3 (the region known to contain the Huntington's disease gene). A panel of seven families was studied, using polymorphic DNA markers, to determine the parental origin of the chromosome abnormality resulting in Wolf-Hirschhorn syndrome. All seven cases were the result of de novo deletions or rearrangements of 4p and in each case the abnormality arose on the paternal chromosome. Analysis of the 3' hypervariable regions of the alpha globin and mucin loci indicated that non-paternity was unlikely to be an explanation for these results. A paternal age effect was not observed. The possibilities of an environmental influence or genetic imprinting require further consideration. This report extends information regarding the preponderance of the paternal origin of de novo structural deletion syndromes.

Adult↗
PubMed1991

Linkage disequilibrium and recombination make a telomeric site for the Huntington's disease gene unlikely.

In a Scottish family in which Huntington's disease (HD) was segregating, recombination was observed between the D4S115/S111 and D4S43/S95 loci, with the HD gene associated with the more proximal D4S43/S95 locus. Analysis of linkage disequilibrium in Scottish families showed significant non-random association between the HD gene and alleles at the D4S95 and D4S98 loci. This adds to previous evidence that the HD locus is not sited at the telomere of chromosome 4.

Alleles↗
PubMed1989

Linkage disequilibrium in Huntington's disease: an improved localisation for the gene.

The search for the Huntington's disease gene has recently concentrated on the telomere of the short arm of chromosome 4. The evidence suggesting this position has been based on single crossover events, but there is conflicting evidence regarding the position of the gene relative to the most terminal markers. We have found significant linkage disequilibrium between the markers D4S98 (probe BS731B-C) and D4S95 (probe BS674E-D) and HD, which supports a localisation for the gene proximal to D4S90 and makes a telomeric localisation unlikely. This disequilibrium may also prove to be important in the future in allowing modification of risk estimates based on genetic linkage.

Alleles↗
PubMed1986

Separation of chromosomal DNA molecules from C.albicans by pulsed field gel electrophoresis.

Modifications have been made to standard pulse field gel electrophoresis (PFGE) systems to enable very large DNA molecules to be resolved. The single most important modification was to elevate the temperature of electrophoresis to 35 degrees C. This enabled the largest Saccharomyces cerevisiae chromosome to be reproducibly resolved. More impressively, it enabled the DNA of Candida albicans to be clearly resolved into six bands, a feat which was very difficult at lower temperatures. Even so, optimal resolution could only be obtained by carefully adjusting field voltages and switching times. The DNA from the two largest C. albicans chromosomes, which was estimated to be at least 5-10Mbp in size, ran somewhat anomalously, giving fuzzy bands which did not migrate in the direction of the average electric field. That the highest molecular weight band was a distinct chromosome was demonstrated by specific hybridisation to the C. albicans ADE2 gene probe. With further fine tuning, the PFGE system described here should be capable of resolving DNA from the smallest human chromosomes.

Candida albicans↗