Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. RESULTS: We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. CONCLUSIONS: Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing

Comprehensive assessment of sequence variation within the copy number variable defensin cluster on 8p23 by target enriched in-depth 454 sequencing

<p>Abstract</p> <p>Background</p> <p>In highly copy number variable (CNV) regions such as the human defensin gene locus, comprehensive assessment of sequence variations is challenging. PCR approaches are practically restricted to tiny fractions, and next-generation sequencing (NGS) approaches of whole individual genomes e.g. by the 1000 Genomes Project is confined by an affordable sequence depth. Combining target enrichment with NGS may represent a feasible approach.</p> <p>Results</p> <p>As a proof of principle, we enriched a ~850 kb section comprising the CNV defensin gene cluster DEFB, the invariable DEFA part and 11 control regions from two genomes by sequence capture and sequenced it by 454 technology. 6,651 differences to the human reference genome were found. Comparison to HapMap genotypes revealed sensitivities and specificities in the range of 94% to 99% for the identification of variations.</p> <p>Using error probabilities for rigorous filtering revealed 2,886 unique single nucleotide variations (SNVs) including 358 putative novel ones. DEFB CN determinations by haplotype ratios were in agreement with alternative methods.</p> <p>Conclusion</p> <p>Although currently labor extensive and having high costs, target enriched NGS provides a powerful tool for the comprehensive assessment of SNVs in highly polymorphic CNV regions of individual genomes. Furthermore, it reveals considerable amounts of putative novel variations and simultaneously allows CN estimation.</p

A gender perspective on factors that influence outdoor recreational physical activity among the elderly

<p>Abstract</p> <p>Background</p> <p>Physical activity (PA) is part of a healthy lifestyle and prevents many chronic health problems, in addition to promoting mental health. PA performed outdoors has been found particularly good for promoting one's well-being. The aim of this study was to investigate the extent to which outdoor recreational PA was carried out during 1 year, and the factors influencing such activities from a gender perspective among persons ≥ 60 years of age.</p> <p>Methods</p> <p>This study included 999 individuals 60-96 years of age living in the south eastern part of Sweden. Data collection was carried out during the years of 2001-2003. We measured the amount of regular light and/or intense outdoor recreational PA performed during the last year and determined the probability of performing PA as a function of 10 variables covering individual and socioeconomic factors.</p> <p>Results</p> <p>Our results suggest that being independent physically and healthy enough to manage one's personal hygiene and having access to areas for country walks were the most important factors associated with the probability of engaging in outdoor recreational PA for both men and women. Despite the level of performance being almost equal for the sexes as two-thirds of both had performed outdoor recreational PA during the preceding year more factors, i.e., living alone, being unable to cover an unexpected cost, fear of being violated, and fear of falling, were associated with the possibilities of engaging in outdoor recreational PA among women. Also increasing age seems to affect activities among women negatively to a higher extent than men.</p> <p>Conclusion</p> <p>Men and women seem to have different opportunities and needs with respect to performing PA. These considerations do not seem to be sufficiently taken into account today and improvements could be made concerning e.g., health-promoting activities suggested to the elderly by healthcare personnel and spatial planning within society. Promoting outdoor recreational PA that has restorative effects on well-being needs to focus on activities which are attractive and affordable for the majority of both men and women.</p

Psychological symptoms

Psychological symptoms are highly prevalent in people requiring palliative care. They are much more challenging to elicit, and more controversy exists about what is normal and what might require intervention than physical symptoms. There are significant issues in determining what is normal and what is not. Sadness, distress, anxiety, and depression can coexist and require careful assessment. Management of psychological symptoms and conditions can broadly be considered in terms of non-pharmacological and pharmacological therapies, “the talking and the drug therapies.” These are not mutually exclusive, and for people with limited energy, failing cognition, and limited time, some pragmatic decisions may be necessary. To be distressed and immobilized by emotion is not normal. Depression is not a normal part of dying. There should be discussion about the nature of psychological issues and conditions, explanation of common somatic symptoms, and a plan for intervention and support. The burden on the carer, both professional and personal, in such situations should not be underestimated.Gregory B. Crawfor

The Fairwork Foundation: strategies for improving platform work in a global context

This paper introduces the Fairwork Foundation, a research initiative that is also developing an intervention around the quality of work on digital labour platforms. Lacking the ability to collectively bargain, many platform workers have little ability to negotiate wages or working conditions with their employers. As a result of this new, digitally-managed market for work, many workers have jobs characterised by long and irregular hours, low income, and high stress. Fairwork's field research across India and South Africa finds challenges for workers across a range of issues which form the basis for a set of decent work principles on: pay, conditions, contracts, management, and representation. The results of the field research are being used to rank and compare platforms against these principles as a means to encourage decent, and discourage ‘un-decent’ platform work

The Move to Online Teaching: A Head of Department’s Perspective

Integrating online teaching strategies within universities is now well established, but there is little on how HE teachers experience this shift. One strand of literature suggests that university senior management teams often assume academic staff lack motivation to participate and resist change. This case study, from a Head of Department’s perspective, challenges that view. Focusing on academics who chose to move to the Open University, an online and distance learning provider, it argues that teaching online requires different skills and presents a fundamental challenge to teacher identity. It concludes that there is a need to both understand the academics’ perspective and acknowledge that there is motivation within the academic community; and support, at all institutional levels, is critical for academics making this transition