Fine mapping of disease genes via haplotype clustering.

We propose an algorithm for analysing SNP-based population association studies, which is a development of that introduced by Molitor et al. [2003: Am J Hum Genet 73:1368-1384]. It uses clustering of haplotypes to overcome the major limitations of many current haplotype-based approaches. We define a between-haplotype score that is simple, yet appears to capture much of the information about evolutionary relatedness of the haplotypes in the vicinity of a (unobserved) putative causal locus. Haplotype clusters can then be defined via a putative ancestral haplotype and a cut-off distance. The number of an individual's two haplotypes that lie within the cluster predicts the individual's genotype at the causal locus. This predicted genotype can then be investigated for association with the phenotype of interest. We implement our approach within a Markov-chain Monte Carlo algorithm that, in effect, searches over locations and ancestral haplotypes to identify large, case-rich clusters. The algorithm successfully fine-maps a causal mutation in a test analysis using real data, and achieves almost 98% accuracy in predicting the genotype at the causal locus. A simulation study indicates that the new algorithm is substantially superior to alternative approaches, and it also allows us to identify situations in which multi-point approaches can substantially improve over single-SNP analyses. Our algorithm runs quickly and there is scope for extension to a wide range of disease models and genomic scales.

Ethical practice in everyday health care

"The public expects members of the medical profession to conduct themselves according to the terms of the Hippocratic oath, yet few physicians and virtually no laypersons know what is iln that oath. For the oath to reach beyond its symbolic importance, ethical conduct must be learned and practised. There are many texts on the practice of medicine, surgery and all of the related disciplines, yet one is hard pressed to find anything on ethical practice in any of them..." "Scholarly texts on ethics tend to deal with the landmark issues and dilemmas that have occurred within particular jurisdictions or religions. This book is intended as a student-friendly text that seeks not to turn students into ethics scholars but to provide them with a practical guide to ethical conduct in everyday medical practice." Ethical Practice in Everyday Health Care is useful, practical and student friendly. The exercise and discussions will stimulate thought about ethical conduct and help students to develop and translate ethical principles into their daily practices as health-care workers. Dr. Waldrond offers a ready and concise source of information for medical students on ethical issues. The text is simple, comprehensive and factual, addressing issues encountered in everyday medical practices. Case studies provide practical illustrations of complex ethical issues (AU)