Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11–q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735–744, 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71371/1/21106_ftp.pd

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Prostate cancer is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity

25-Year Record of Nutrient Loading to a Large, Oligotrophic Lake -- Flathead Lake

Flathead Lake is one of the 300 largest lakes in the world. The Flathead Basin is 22,241 sq. km and is drained by six 5th-order tributaries of the main-stem Flathead River. Almost half (42%) of the Basin is included in National Park and Wilderness protection. Nutrient loading to Flathead Lake from all major tributaries and atmospheric deposition was measured over a period of 25 years. During the last two decades as much as 45% of the annual phosphorus and 24% of the nitrogen load was fallout from the atmosphere, mainly from fugitive dust from local rural roads, smoke particulates from forest fires and agricultural burning inside and often far outside the Flathead Basin. Pelagic primary production (in-lake growth of algae) is limited by availability of nitrogen and phosphorus. Nitrogen loading from human sources upstream of Flathead Lake has steadily increased over the last three decades, and daily nitrogen loading weakly correlates with increasing primary production. Presenter: Scott Relyea of the Flathead Lake Biological Statio

Long-term atmospheric deposition of nitrogen, phosphorus and sulfate in a large oligotrophic lake

We documented significantly increasing trends in atmospheric loading of ammonium (NH4) and nitrate/nitrite (NO2/3) and decreasing trends in total phosphorus (P) and sulfate (SO4) to Flathead Lake, Montana, from 1985 to 2004. Atmospheric loading of NO2/3 and NH4 increased by 48 and 198% and total P and SO4 decreased by 135 and 39%. The molar ratio of TN:TP also increased significantly. Severe air inversions occurred periodically year-round and increased the potential for substantial nutrient loading from even small local sources. Correlations between our loading data and various measures of air quality in the basin (e.g., particulate matter <10 µm in size, aerosol fine soil mass, aerosol nutrient species, aerosol index, hectares burned) suggest that dust and smoke are important sources. Ammonium was the primary form of N in atmospheric deposition, whereas NO3 was the primary N form in tributary inputs. Atmospheric loading of NH4 to Flathead Lake averaged 44% of the total load and on some years exceeded tributary loading. Primary productivity in the lake is colimited by both N and P most of the year; and in years of high atmospheric loading of inorganic N, deposition may account for up to 6.9% of carbon converted to biomass

Merits and Limits of Ecosystem Protection for Conserving Wild Salmon in a Northern Coastal British Columbia River

Loss and degradation of freshwater habitat reduces the ability of wild salmon populations to endure other anthropogenic stressors such as climate change, harvest, and interactions with artificially propagated fishes. Preservation of pristine salmon rivers has thus been advocated as a cost-effective way of sustaining wild Pacific salmon populations. We examine the value of freshwater habitat protection in conserving salmon and fostering resilience in the Kitlope watershed in northern coastal British Columbia - a large (3186 km2) and undeveloped temperate rainforest ecosystem with legislated protected status. In comparison with other pristine Pacific Rim salmon rivers we studied, the Kitlope is characterized by abundant and complex habitats for salmon that should contribute to high resilience. However, biological productivity in this system is constrained by naturally cold, light limited, ultra-oligotrophic growing conditions; and the mean (± SD) density of river-rearing salmonids is currently low (0.32 ± 0.27 fish per square meter; n = 36) compared to our other four study rivers (grand mean = 2.55 ± 2.98 fish per square meter; n = 224). Existing data and traditional ecological knowledge suggest that current returns of adult salmon to the Kitlope, particularly sockeye, are declining or depressed relative to historic levels. This poor stock status - presumably owing to unfavorable conditions in the marine environment and ongoing harvest in coastal mixed-stock fisheries - reduces the salmon-mediated transfer of marine-derived nutrients and energy to the system's nutrient-poor aquatic and terrestrial food webs. In fact, Kitlope Lake sediments and riparian tree leaves had marine nitrogen signatures (δ15N) among the lowest recorded in a salmon ecosystem. The protection of the Kitlope watershed is undoubtedly a conservation success story. However, "salmon strongholds" of pristine watersheds may not adequately sustain salmon populations and foster social and ecological resilience without more holistic and risk-averse management that accounts for uncertainty and interactions between ecosystem fertility, harvest, climate dynamics, and food web dynamics in the marine and freshwater environments encompassed by the life cycle of the fish

A Patchy Hierarchy Approach to Modeling Surface and Subsurface Hydrology in Complex Flood-plain Environments

Geomorphology interacts with surface- and ground-water hydrology across multiple spatial scales. Nonetheless, hydrologic and hydrogeologic models are most commonly implemented at a single spatial scale. Using an existing hydrogeologic computer model, we implemented a simple hierarchical approach to modeling surface- and ground-water hydrology in a complex geomorphic setting. We parameterized the model to simulate ground- and surface-water flow patterns through a hierarchical, three-dimensional, quantitative representation of an anabranched montane alluvial flood plain (the Nyack Flood Plain, Middle Fork Flathead River, Montana, USA). Comparison of model results to field data showed that the model provided reasonable representations of spatial patterns of aquifer recharge and discharge, temporal patterns of flood-water storage on the flood plain, and rates of ground-water movement from the main river channel into a large lateral spring channel on the flood plain, and water table elevation in the alluvial aquifer. These results suggest that a hierarchical approach to modeling ground- and surface-water hydrology can reproduce realistic patterns of surface- and ground-water flux on alluvial flood plains, and therefore should provide an excellent ‘quantitative laboratory’ for studying complex interactions between geomorphology and hydrology at and across multiple spatial scales

Arts with offenders: A literature synthesis

This article applies systematic review and meta-synthesis techniques to research studies (qualitative and quantitative) with the aim of addressing the research question of: do the arts have any role to play in therapeutic goals for offenders? While arts and arts therapies are used in various offender contexts research has been variable in purpose, style and rigour. This is the first systematic attempt to compile a literature synthesis concerning the role of arts with offender populations. A systematic review and literature synthesis of both qualitative and quantitative studies was conducted, with a focus on systematic research addressing questions either of efficacy / effectiveness, or of the nature and experience of arts practice with offenders. Notwithstanding methodological shortcomings, arts and arts therapies were invariably found to be associated with improvements in arousal levels, emotional literacy, and quality of life. While both qualitative and quantitative reports tend to focus on the same broad issues identified in this literature synthesis, they communicate these findings using very different language. The authors recommend a mixed methods approach in future research, to facilitate an understanding of the effects of arts with offenders through different lenses and measure their long term effects on offender behaviour