1,721,269 research outputs found
Sharp, Andrew, ed. The Journal of Roggeveen
No full textLaroche Marie-Charlotte. Sharp, Andrew, ed. The Journal of Roggeveen. In: Journal de la Société des océanistes, n°34, tome 28, 1972. pp. 94-95
Sharp, Andrew, ed. The Journal of Roggeveen
No full textLaroche Marie-Charlotte. Sharp, Andrew, ed. The Journal of Roggeveen. In: Journal de la Société des océanistes, n°34, tome 28, 1972. pp. 94-95
Sharp, Andrew. The Voyages of Abel Janszoon Tasman
No full textFaivre Jean-Paul. Sharp, Andrew. The Voyages of Abel Janszoon Tasman. In: Journal de la Société des océanistes, tome 24, 1968. p. 158
Sharp, Andrew. The Voyages of Abel Janszoon Tasman
No full textFaivre Jean-Paul. Sharp, Andrew. The Voyages of Abel Janszoon Tasman. In: Journal de la Société des océanistes, tome 24, 1968. p. 158
The impact of ageing upon the attitudes and behaviour of elderly residents in McCarthy and Stone private sheltered housing
No full textSIGLEAvailable from British Library Document Supply Centre- DSC:DX85573 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
A molecular study of X chromosome inactivation in humans
No full textAvailable from British Library Document Supply Centre- DSC:DXN059933 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation
No full textWe have analysed the spread of X inactivation in an individual with an unbalanced 46,X,der(X)t(X;10)(q26.3;q23.3) karyotype. Despite being trisomic for the region 10q23.3-qter, both the proband and her aunt with the same karyotype presented only with secondary amenorrhoea and lacked any features normally associated with trisomy of distal 10q. Cytogenetic and molecular studies showed that the derivative X;10 chromosome was exclusively inactive. Transcribed polymorphisms were identified in five genes contained within the translocated region of chromosome 10 and were used to perform allele-specific transcription studies. We showed that four of the genes studied are inactive on the derivative chromosome, directly demonstrating the spread of X inactivation over some 30 Mb of autosomal DNA. However, the most distal gene examined remained active, indicating that this spreading was incomplete. In contrast to the gene expression data, replication timing studies showed no spreading of late replication into the translocated portion of 10q. We conclude that silencing of autosomal genes by X inactivation can occur without a delay in the replication timing of the surrounding chromatin. Our findings support the hypothesis that autosomal chromatin lacks certain features present on the X chromosome that are required for the effective spread and/or maintenance of X inactivatio
RNA analysis reveals splicing mutations and loss of expression defects in MLH1 and BRCA1
No full textThe classical paradigm of mutation screening seeks to relate alterations in DNA sequence to their effect at the protein level. However, the majority of missense mutations are problematic as their pathological significance is often unclear. In order to test the hypothesis that many missense mutations primarily cause defects at the RNA rather than the protein level, we have performed retrospective RNA analysis of 12 individuals carrying missense mutations in the cancer predisposition genes APC, BRCA1, BRCA2, MLH1, and MSH2. RNA was extracted from peripheral blood samples and RT-PCR performed in order to assess the splicing and expression of the mutant allele in each case. Four of the 12 missense mutations analysed were associated with RNA defects. We detected two cases of exon skipping and one case of partial intron inclusion with activation of a cryptic intronic splice site in MLH1. A fourth case was associated with monoallelic expression of BRCA1. In addition, allele-specific analysis of common coding polymorphisms identified a further case of monoallelic BRCA1 expression in one of two individuals who had previously screened as mutation-negative. Although we were unable to identify the underlying cause of this loss of expression, it strongly suggests the presence of a pathogenic defect in BRCA1 in this case, highlighting the use of allelic expression studies as a method of mutation scanning. Finally, we used our dataset to test the ability of several in silico sequence analysis tools to identify splicing defects. Our results suggest that a significant number of missense mutations in cancer predisposition genes are associated with defects of RNA splicing, and that the use of gene- and splice site prediction software can aid in identifying such mutations
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