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Current genome-wide association studies (GWAS) have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE). This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders), and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated. [ABSTRACT FROM AUTHOR]

This paper is a phenomenological examination of Nova Scotian teachers leading children outside the normal school environment for instructional purposes. Phenomenology can examine the everyday, taken-for-granted phenomena in human experiences. Absent in experiential research is the focus on teachers' experience in outside programs. In addressing this gap, anecdotes that capture unique elements of pedagogic intensity are shared as insight into the lifeworld of outdoor educators. Common to all the teachers in this study were feelings of intensity. These lived experiences are from various disciplines, at the senior high school level, and the teachers are engaged in outdoor practices connected to their respective subject areas. These teachers share past moments that show pedagogic intensity as a varied and unique instructional experience. All the teachers observed that the outdoors somehow magnifies the teaching experience. A key area is how this magnification applies to the pedagogic quality of outside teaching. [ABSTRACT FROM AUTHOR]