Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no deleterious coding or splice site changes

<p>Abstract</p> <p>Background</p> <p>A subset of cutaneous malignant melanoma and dysplastic nevi (CMM/DN) families is linked to 1p36. To date, no CMM/DN susceptibility gene has been identified at this locus. Data from mouse studies identified chromodomain helicase DNA binding protein 5 (<it>CHD5</it>) as a tumor suppressor affecting cellular proliferation and apoptosis via the <it>CDKN2A</it>/p53 pathway. Based on these findings, we felt it was important to screen <it>CHD5 </it>as a familial CMM/DN susceptibility gene.</p> <p>Methods</p> <p>Eight unrelated CMM/DN families showing prior evidence of linkage to the 1p36 locus were identified for <it>CHD5 </it>mutation screening. One CMM/DN affected and one unaffected individual from each family were selected for sequencing of the <it>CHD5 </it>coding exons and their respective intron-exon boundaries. <it>CHD5 </it>variants that were identified solely among affecteds in the screening panel were further assessed by sequencing additional affected and unaffected members of these families to determine if the variant co-segregated with the CMM/DN phenotype.</p> <p>Results</p> <p>Single nucleotide polymorphisms in the <it>CHD5 </it>intronic and coding regions were identified among affecteds in the screening panel. None of these variants completely co-segregated with CMM/DN affection status among these eight families.</p> <p>Conclusion</p> <p>There is no evidence to support <it>CHD5 </it>as a major melanoma susceptibility gene among the eight CMM/DN families screened.</p

Application of 3D Laser Scanning to the Preservation of Fort Conger, a Historic Polar Research Base on Northern Ellesmere Island, Arctic Canada

Fort Conger, located in Quttinirpaaq National Park, Ellesmere Island, is a historic landmark of national and international significance. The site is associated with many important Arctic expeditions, including the ill-fated Lady Franklin Bay Expedition of the First International Polar Year and Robert Peary’s attempts to claim the North Pole. Although situated in one of the most remote locations on earth, Fort Conger is currently at risk because of the effects of climate change, weather, wildlife, and human activity. In this paper, we show how 3D laser scanning was used to record cultural features rapidly and accurately despite the harsh conditions present at the site. We discuss how the future impacts of natural processes and human activities can be managed using 3D scanning data as a baseline, how conservation and restoration work can be planned from the resulting models, and how 3D models created from laser scanning data can be used to excite public interest in cultural stewardship and Arctic history.Fort Conger, situé dans le parc national Quttinirpaaq, sur l’île d’Ellesmere, est un lieu historique d’importance nationale et internationale. Ce site est lié à de nombreuses expéditions arctiques importantes, dont l’infortunée expédition de la baie Lady Franklin relevant de la première année polaire internationale et les tentatives de revendication du pôle Nord par Robert Peary. Bien qu’il se trouve dans l’un des endroits les plus éloignés du globe, Fort Conger subit actuellement les risques découlant des effets du changement climatique, des conditions météorologiques, de la faune et de l’activité humaine. Dans cette communication, nous montrons comment un scanneur laser 3D a permis de répertorier les caractéristiques culturelles avec rapidité et précision malgré les conditions difficiles qui ont cours à ce site. Nous discutons de la manière dont les incidences futures des processus naturels et de l’activité humaine peuvent être gérées à l’aide des données 3D comme données de base, comment les travaux de conservation et de restauration peuvent être planifiés à partir des modèles qui en résultent et comment les modèles 3D créés à partir des données de scannage laser peuvent rehausser l’intérêt du grand public à l’égard de la gérance culturelle et de l’histoire de l’Arctique

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^&#x3e;0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Public attitudes towards pricing policies to change health-related behaviours: a UK focus group study.

BACKGROUND: Evidence supports the use of pricing interventions in achieving healthier behaviour at population level. The public acceptability of this strategy continues to be debated throughout Europe, Australasia and USA. We examined public attitudes towards, and beliefs about the acceptability of pricing policies to change health-related behaviours in the UK. The study explores what underlies ideas of acceptability, and in particular those values and beliefs that potentially compete with the evidence presented by policy-makers. METHODS: Twelve focus group discussions were held in the London area using a common protocol with visual and textual stimuli. Over 300,000 words of verbatim transcript were inductively coded and analyzed, and themes extracted using a constant comparative method. RESULTS: Attitudes towards pricing policies to change three behaviours (smoking, and excessive consumption of alcohol and food) to improve health outcomes, were unfavourable and acceptability was low. Three sets of beliefs appeared to underpin these attitudes: (i) pricing makes no difference to behaviour; (ii) government raises prices to generate income, not to achieve healthier behaviour and (iii) government is not trustworthy. These beliefs were evident in discussions of all types of health-related behaviour. CONCLUSIONS: The low acceptability of pricing interventions to achieve healthier behaviours in populations was linked among these responders to a set of beliefs indicating low trust in government. Acceptability might be increased if evidence regarding effectiveness came from trusted sources seen as independent of government and was supported by public involvement and hypothecated taxation.The study was funded by the UK Department of Health Policy Research Programme (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109]). The Department of Health had no role in the study design, data collection, analysis, or interpretation. The research was conducted independently of the funders, and the views expressed in this paper are those of the authors and not necessarily those of the Department of Health in England.This is the final version of the article. It was first available from Oxford University Press at http://dx.doi.org/10.1093/eurpub/ckv07

Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P(SNP-trend)) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P(Region) and P(Pathway)) were assessed by combining individual P(SNP-trend) values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P(SNP-FDR)/P(SNP-trend) = 0.02/6×10(−6) and P(SNP-FDR)/P(SNP-trend) = 0.04/2×10(−5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P(Region-FDR)/P(Region = )0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P(Pathway) = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC

Strategies to optimize the impact of nutritional surveys and epidemiological studies

The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health

Improving health services for African migrants in China: A health diplomacy perspective

Global health has been an increasingly prominent component of foreign policy in the last decade. The term health diplomacy has been used to describe this growing interface between foreign policy and global health, and it encompasses both the concept of using health to further foreign policy objectives, as well as the idea that diplomatic tools can be helpful for attaining public health goals. The Chinese presence in Africa has grown in the last 15 years, generating increased interest in Sino-African relations. While much has been written in recent years about the Chinese presence in Africa, the growing numbers of Africans in China have attracted considerably less attention. Many are small-scale traders and might be expected to face many of the health challenges common among foreign migrants, but their health needs have been largely unrecognised. In this paper, we consider how a health diplomacy approach could be applied to African migrants in China, and the potential advantages and limitations of this strategy. We identify areas of overlap between public health, trade, and foreign policy goals that can be emphasised to generate support for improved services for African migrants in China and to engage partners from a diversity of sectors

Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations

Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. Materials and Methods We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction. Discussion Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk

Determining origin in a migratory marine vertebrate: a novel method to integrate stable isotopes and satellite tracking

Stable isotope analysis is a useful tool to track animal movements in both terrestrial and marine environments. These intrinsic markers are assimilated through the diet and may exhibit spatial gradients as a result of biogeochemical processes at the base of the food web. In the marine environment, maps to predict the spatial distribution of stable isotopes are limited, and thus determining geographic origin has been reliant upon integrating satellite telemetry and stable isotope data. Migratory sea turtles regularly move between foraging and reproductive areas. Whereas most nesting populations can be easily accessed and regularly monitored, little is known about the demographic trends in foraging populations. The purpose of the present study was to examine migration patterns of loggerhead nesting aggregations in the Gulf of Mexico (GoM), where sea turtles have been historically understudied. Two methods of geographic assignment using stable isotope values in known-origin samples from satellite telemetry were compared: (1) a nominal approach through discriminant analysis and (2) a novel continuous-surface approach using bivariate carbon and nitrogen isoscapes (isotopic landscapes) developed for this study. Tissue samples for stable isotope analysis were obtained from 60 satellite-tracked individuals at five nesting beaches within the GoM. Both methodological approaches for assignment resulted in high accuracy of foraging area determination, though each has advantages and disadvantages. The nominal approach is more appropriate when defined boundaries are necessary, but up to 42% of the individuals could not be considered in this approach. All individuals can be included in the continuous-surface approach, and individual results can be aggregated to identify geographic hotspots of foraging area use, though the accuracy rate was lower than nominal assignment. The methodological validation provides a foundation for future sea turtle studies in the region to inexpensively determine geographic origin for large numbers of untracked individuals. Regular monitoring of sea turtle nesting aggregations with stable isotope sampling can be used to fill critical data gaps regarding habitat use and migration patterns. Probabilistic assignment to origin with isoscapes has not been previously used in the marine environment, but the methods presented here could also be applied to other migratory marine species