Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Living on the threshold: The spatial experience of living alone with dementia

The purpose of this qualitative study was to understand the meaning of living alone for older people with dementia. Fourteen audio-taped open-ended interviews were conducted with eight such older women in Ontario, Canada. The data were analyzed using an adaptation of van Manen\u27s method. Heidegger\u27s philosophy informed interpretation of the findings through the theme living on the threshold. The study findings deepen understanding of \u27space\u27 and \u27place\u27 in the experience of living alone with dementia. Participants sought the middle-ground of dialectical tensions within the threshold space and shared insights about their spatial experience of: (a) being here, (b) being there, (c) being out, and (d) keeping out. These older women risked losing their threshold space when admitting to mistakes as their illness progressed. The authors conclude with examples of how this spatial interpretation may inform and improve communication with and care of older people in similar circumstances. © The Author(s), 2009

You\u27re saying something by giving things to them: communication and family inheritance

The study purpose was to contribute to a more complete understanding of the experience and meaning of family inheritance. The aim of this article is to describe and discuss the meaning of communication in inheritance experiences among Canadian families. A constructivist/interpretive methodological approach guided this research. Participants were recruited through purposive, convenience sampling from two cities and one town in southern and southwestern Ontario, Canada. Fifty face-to-face, semi-structured, audio-taped, in-depth interviews were conducted between June 2006 and April 2007. NVivo software was used to organize and analyze the data. A content analysis method guided data analysis. Participants interpreted the meaning of family structure, relationships, feelings, and past inheritance experiences to construct their family inheritance communication. Analysis of the findings revealed four themes regarding the role of communication in family inheritance including: (a) avoiding conflict and preserving biological ties, (b) resisting conversations about possessions, (c) achieving confidence with possession communication, and (d) lasting effects. Participants from non-blended and blended families experienced similar inheritance communication challenges related to past experience with their parents\u27 wills and distribution of their own possessions. Participants with past positive inheritance experiences with parents adopted similar strategies when communicating their own inheritance wishes. Negative messages conveyed to participants by their parent\u27s wills inspired participants to communicate in opposite ways in their own inheritance planning. The study findings are useful for gerontologists, lawyers, family counselors, and estate planners. © 2013 Springer-Verlag Berlin Heidelberg

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase