28 research outputs found

    No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

    Get PDF
    BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community®s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

    Quality management for vital forest tree seedlings : Final report, Project no: P33854-1

    No full text
    The work concerns development of a prototype molecular tests to identify vitality status of conifer seedlings. The work is done by NSure, Holland, Dalarna University and SUAS. In case for spruce, a successful validation experiment has been performed to validate the identified frost tolerance and vitality genes. Multiple indicators were identified that can be used to either reinforce the existing ColdnSure test, but also for development of a vitality test. The identified frost tolerance and vitality genes for pine still need to be validated. NSure together with Dalarna University aim to perform a validation next season. Multiple LN indicators were identified in spruce that can be used to determine the effectiveness of a LN treatment, but they are not yet validated. In spruce and pine hardly any scientific research is performed to study the effect of a LN treatment, particularly not at molecular level. Therefore NSure together with Dalarna Research Station want to apply for a project. Within this project, we would be able to develop the tests further

    Short-day photoperiods affect expression of genes related to dormancy and freezing tolerance in Norway spruce seedlings

    Get PDF
    Key message: Gene expression analysis showed that prolonged short day (SD) treatment deepened dormancy and stimulated development of freezing tolerance of Picea abies seedlings. Prolonged SD treatment also caused later appearance of visible buds in autumn, reduced risks for reflushing, and promoted earlier spring bud break. Context: Short day (SD) treatment of seedlings is a common practice in boreal forest tree nurseries to regulate shoot growth and prepare the seedlings for autumn planting or frozen storage. Aims The aim of this study was to examine responses of Norway spruce (Picea abies (L.) Karst.) to a range of SD treatments of different length and evaluate gene expression related to dormancy induction and development of freezing tolerance. Methods: The seedlings were SD treated for 11 h a day during 7, 14, 21, or 28 days. Molecular tests were performed, and the expression profiles of dormancy and freezing tolerance- related genes were analyzed as well as determination of shoot growth, bud set, bud size, reflushing, dry matter content, and timing of spring bud break. Results: The 7-day SD treatment was as effective as longer SD treatments in terminating apical shoot growth. However, short (7 days) SD treatment resulted in later activation of dormancy-related genes and of genes related to freezing tolerance compared to the longer treatments which had an impact on seedling phenology. Conclusion: Gene expression analysis indicated an effective stimulus of dormancy-related genes when the SD treatment is prolonged for at least 1-2 weeks after shoot elongation has terminated and that seedlings thereafter are exposed to ambient outdoor climate conditions

    Evaluating methods for storability assessment and determination of vitality status of container grown Norway spruce transplants after frozen storage

    No full text
    Autumn sown small seedlings for later transplanting into large containers have been introduced in Swedish forest tree nurseries. Containerized transplants of Norway spruce (Picea abies (L.) Karst.) from three Swedish nurseries were frozen stored during the autumn of 2014 to find out storability and post-storage vitality. Seedling storability was determined by measuring electrolyte leakage after freezing shoots to −25°C (SELdiff−25), by measurements of dry matter content (DMC) of seedling shoots and by the commercial molecular test ColdNSureℱ. Vitality of seedlings after storage was determined by measuring the leakage of electrolytes from shoots (SEL), and seedlings were also tested in regrowth tests. All three methods for storability assessment gave similar predictions, except in one case where DMC showed “not storable” for successfully stored seedlings. Our results indicated that young transplants can be successfully short term stored before reaching the target levels for safe long-term storage of conventional seedlings. Early storage of young transplants resulted in low post-storage survival and vitality expressed as root growth capacity and shoot electrolyte leakage (SEL). A prolonged duration in storage generally resulted in lower survival as well as lower root growth capacity and higher levels of SEL, especially for seedlings stored at earlier dates.

    Year-Round Prevalence of Norovirus in the Environment of Catering Companies without a Recently Reported Outbreak of Gastroenteritis▿

    No full text
    Food handlers play an important role in the transmission of norovirus (NoV) in food-borne outbreaks of gastroenteritis (GE). In a year-round prevalence study, the prevalence of NoV in catering companies without recently reported outbreaks of GE was investigated and compared to the observed prevalence in catering companies with recently reported outbreaks. Swab samples were collected from surfaces in the kitchens and (staff) bathrooms in 832 randomly chosen companies and analyzed for the presence of NoV RNA. In total, 42 (1.7%) out of 2,496 environmental swabs from 35 (4.2%) catering companies tested positive. In contrast, NoV was detected in 147 (39.7%) of the 370 samples for 44 (61.1%) of the 72 establishments associated with outbreaks of gastroenteritis. NoV-positive swabs were more frequently found in winter, in specific types of companies (elderly homes and lunchrooms), and in establishments with separate bathrooms for staff. We found a borderline association with population density but no relation to the number of employees. Sequence analysis showed that environmental strains were interspersed with strains found in outbreaks of illness in humans. Thus, the presence of NoV in catering companies seemed to mirror the presence in the population but was strongly increased when associated with food-borne GE. Swabs may therefore serve as a valuable tool in outbreak investigations for the identification of the causative agent, although results should be interpreted with care, taking into account all other epidemiological data
    corecore