Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation

Background: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals. Methods: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established. Results: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher’s exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1–4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5′ end of the gene. Conclusions: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD

Crop Updates 2000 Cereals - part 4

This session covers twelve papers from different authors: BREEDING 1.Response to subsoil acidity of wheat genotypes differing in Al-tolerance, C. Tang, Z. Rengel, E. Diatloff and B. McGann, Soil Science and Plant Nutrition/CLIMA, University of Western Australia 2. Application of molecular markers in Barley Improvement, Mehmet Cakir1, Nick Galwey1 and David Poulsen2, 1Plant Sciences, Faculty of Agriculture, University of Western Australia, 2Queensland Department of Primary Industries, Hermitage Research Station, Queensland 3. Implementation of molecular markers for wheat improvement in the Western Region, M. Carter1, A. Briney1, R. Wilson2, R.H. Potter1 and M.G.K. Jones1, 1Western Australian State Agricultural Biotechnology Centre, Murdoch University, 2Crop Industries, Agriculture Western Australia 4. Performance in 1999 of recently released wheat varieties in Western Australia, Robin Wilson, Iain Barclay, Robyn McLean, Dean Diepeveen and Robert Loughman, Agriculture Western Australia ECONOMICS 5. Outlook for prices and implications for rotations, Ross Kingwell1 2, Michael O’Connell1, Simone Blennerhasset1 1Agriculture Western Australia, 2University of Western Australia 6. Price Risk Management and the Western Australian Grain Producer, Benjamin Michael Tiller, Muresk Institute of Agriculture FORECASTING 7. Can we forecast wheat yields in Western Australia, Senthold Asseng1, Holger Meinke2, and Bill Bowden3, 1CSIRO Plant Industry, 2 APSRU/DPI, 3Agriculture Western Australia ON FARM TESTING 8. On-farm testing, the quiet revolution continues, Jeff Russell1, Ivan Lee2 1Agriculture Western Australia, 2 Farmer Kunjin TopCrop group, Corrigin GRAIN STORAGE 9. CD-ROM tool for growers and advisers: Managing on-farm grain storage – effective practices for the delivery of quality assured products, Clare Johnson1, Chris Newman2 1Quality Wheat CRC Ltd, 2Production Resource Protection Services, Agriculture Western Australia 10. The Internet as a tool for managing grain insects, Robert Emery, Romolo Tassone and Ernestos Kostas, Agriculture Western Australia SUMMER CROPS AND WINDBREAK EFFECT ON YIELD 11. Summer crop Update and agronomic considerations, Graeme Ralph, Pioneer Hi-Bred Australia Pty Ltd 12. The effect of tree windbreaks on grain yield in the medium and low rainfall areas in Western Australia, Robert Sudmeyer, David Hall and Harvey Jones, Agriculture Western Australi

A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response

Crop Updates 2000 Cereals - part 4

This session covers twelve papers from different authors: BREEDING 1.Response to subsoil acidity of wheat genotypes differing in Al-tolerance, C. Tang, Z. Rengel, E. Diatloff and B. McGann, Soil Science and Plant Nutrition/CLIMA, University of Western Australia 2. Application of molecular markers in Barley Improvement, Mehmet Cakir1, Nick Galwey1 and David Poulsen2, 1Plant Sciences, Faculty of Agriculture, University of Western Australia, 2Queensland Department of Primary Industries, Hermitage Research Station, Queensland 3. Implementation of molecular markers for wheat improvement in the Western Region, M. Carter1, A. Briney1, R. Wilson2, R.H. Potter1 and M.G.K. Jones1, 1Western Australian State Agricultural Biotechnology Centre, Murdoch University, 2Crop Industries, Agriculture Western Australia 4. Performance in 1999 of recently released wheat varieties in Western Australia, Robin Wilson, Iain Barclay, Robyn McLean, Dean Diepeveen and Robert Loughman, Agriculture Western Australia ECONOMICS 5. Outlook for prices and implications for rotations, Ross Kingwell1 2, Michael O’Connell1, Simone Blennerhasset1 1Agriculture Western Australia, 2University of Western Australia 6. Price Risk Management and the Western Australian Grain Producer, Benjamin Michael Tiller, Muresk Institute of Agriculture FORECASTING 7. Can we forecast wheat yields in Western Australia, Senthold Asseng1, Holger Meinke2, and Bill Bowden3, 1CSIRO Plant Industry, 2 APSRU/DPI, 3Agriculture Western Australia ON FARM TESTING 8. On-farm testing, the quiet revolution continues, Jeff Russell1, Ivan Lee2 1Agriculture Western Australia, 2 Farmer Kunjin TopCrop group, Corrigin GRAIN STORAGE 9. CD-ROM tool for growers and advisers: Managing on-farm grain storage – effective practices for the delivery of quality assured products, Clare Johnson1, Chris Newman2 1Quality Wheat CRC Ltd, 2Production Resource Protection Services, Agriculture Western Australia 10. The Internet as a tool for managing grain insects, Robert Emery, Romolo Tassone and Ernestos Kostas, Agriculture Western Australia SUMMER CROPS AND WINDBREAK EFFECT ON YIELD 11. Summer crop Update and agronomic considerations, Graeme Ralph, Pioneer Hi-Bred Australia Pty Ltd 12. The effect of tree windbreaks on grain yield in the medium and low rainfall areas in Western Australia, Robert Sudmeyer, David Hall and Harvey Jones, Agriculture Western Australi