Sushi gets serious:the draft genome sequence of the pufferfish Fugu rubripes

The publication of the Fugu rubripes draft genome sequence will take this fish from culinary delicacy to potent tool in deciphering the mysteries of human genome function

The genomic signature of trait-associated variants

BACKGROUND: Genome-wide association studies have identified thousands of SNP variants associated with hundreds of phenotypes. For most associations the causal variants and the molecular mechanisms underlying pathogenesis remain unknown. Exploration of the underlying functional annotations of trait-associated loci has thrown some light on their potential roles in pathogenesis. However, there are some shortcomings of the methods used to date, which may undermine efforts to prioritize variants for further analyses. Here, we introduce and apply novel methods to rigorously identify annotation classes showing enrichment or depletion of trait-associated variants taking into account the underlying associations due to co-location of different functional annotations and linkage disequilibrium. RESULTS: We assessed enrichment and depletion of variants in publicly available annotation classes such as genic regions, regulatory features, measures of conservation, and patterns of histone modifications. We used logistic regression to build a multivariate model that identified the most influential functional annotations for trait-association status of genome-wide significant variants. SNPs associated with all of the enriched annotations were 8 times more likely to be trait-associated variants than SNPs annotated with none of them. Annotations associated with chromatin state together with prior knowledge of the existence of a local expression QTL (eQTL) were the most important factors in the final logistic regression model. Surprisingly, despite the widespread use of evolutionary conservation to prioritize variants for study we find only modest enrichment of trait-associated SNPs in conserved regions. CONCLUSION: We established odds ratios of functional annotations that are more likely to contain significantly trait-associated SNPs, for the purpose of prioritizing GWAS hits for further studies. Additionally, we estimated the relative and combined influence of the different genomic annotations, which may facilitate future prioritization methods by adding substantial information

Bases and spaces: resources on the web for accessing the draft human genome

Much is expected of the draft human genome sequence, and yet there is no central resource to host the plethora of sequence and mapping information available. Consequently, finding the most useful and reliable human genome data and resources currently available on the web can be challenging, but is not impossible

Bases and spaces: resources on the web for accessing the draft human genome - II - After publication of the draft

The volume of human genome sequence and the variety of web-based tools to access it continue to grow at an impressive rate, but a working knowledge of certain key resources can be sufficient to get the most from your genome. This article provides an update to Genome Biology 2000, 1(4):reviews2001.1-2001.5

Androgens in Men During Illness, Exercise and Psychological Stress

My early clinical experience had demonstrated that abnormalities of endocrine testing particularly with regards to thyroid function are common in ill patients. Interest in endocrine effects of illness was further stimulated by my study of hormone levels of uraemic patients undergoing differing forms of dialysis therapy. Chronic renal failure resulted in abnormal hypothalamic-pituitary-testicular and hypothalamic-pituitary-thyroid function irrespective of the nature of dialysis. Evidence for low levels of adrenal androgen in serum of uraemic patients was also found. As it was well known that abnormalities of thyroid function occurred in a variety of illnesses so it appeared possible that abnormalities of adrenal androgen status and hypothalamic-pituitary-testicular function might also be non-specific consequences of illness. To investigate this hypothesis these endocrine parameters were measured in several groups of patients:- those ill in a general medical ward, in diabetic men with ketoacidosis, during recovery from burns injury and before and after surgery. Serum levels of the most abundant adrenal androgen dehydroepiandrosterone sulphate (DHAS) were low in patients with a variety of non-endocrine medical illnesses only if they had been unwell for more than two weeks while serum androstenedione concentrations were higher than in controls irrespective of the duration of illness. Testosterone levels were also low but this was not related to the duration or severity of illness nor could it be accounted for by changes in binding proteins, hyperprolactinaemia nor on the basis of classical primary or secondary testicular failure. A study of men during an episode of diabetic ketoacidosis revealed that this complication of diabetes mellitus is also accompanied by depression of serum testosterone concentrations. However serum testosterone concentrations of non-ketotic diabetic men at routine review were not found to be related to diabetic control as assessed by glycosylated haemoglobin estimation. There was some limited evidence in the literature to suggest that adrenal androgen levels in diabetic men might be low and that this might have a deleterious effect on islet cell function but no abnormality of these hormones could be demonstrated in this group of patients. 19 burned men were followed sequentially for several weeks. Profound depression of serum testosterone concentrations for several weeks was found with levels falling into the range found in healthy females in the majority of patients studied. This could not be explained on the basis of binding protein changes nor by alterations in the concentrations of prolactin or gonadotrophins. DHAS levels although normal within 24 hours of admission fell to subnormal levels and remained low for several weeks. Serum androstenedione levels were high following admission and tended to remain so for several weeks. These changes in adrenal androgen concentrations were reminiscent of my observations during medical illness. Serum gonadotrophin levels of post-menopausal females were studied following cholecystectomy. Unlike the situation in medically ill men this operation led to a marked reduction in gonadotrophin levels sometimes down to the pre-menopausal range. Serum DHAS levels fell to below control values four days after surgery while serum androstenedione concentrations rose transiently post-operatively. The situation was however complicated by the administration of several drugs in particular parenteral opioids which might have affected gonadotrophin levels. As such profound endocrine changes had been observed with illness, it was of interest to discover whether these were specific to illness or whether other forms of stress such as the physical stress associated with exercise or the psychological stress accompanying academic examinations might result in similar changes. Following marathon running there was a small fall in serum testosterone concentrations. The situation differed from that following illness in that there was a massive elevation of serum cortisol as well as a fall in luteinising hormone (LH) levels. On the other hand veteran athletes who had run at least 25 miles a week for many years and who are therefore exposed to recurring and chronic physical stress had normal serum testosterone levels. Neither veteran athletes nor marathon runners showed evidence of a reduction in serum concentrations of adrenal androgens. The stress of physical exercise has a short-lived adverse effect on testicular function but unlike illness there are no changes in adrenal androgen levels. Review of the literature suggested that psychological stress can adversely affect gonadal function. (Abstract shortened by ProQuest.)

English Common Law, Slavery, and Human Rights

This paper considers the issues of villeinage and slavery in England and the British colonies; the decision in Somerset v. Stewart\u27 and other cases in English common law courts; the application of English common law in the colonies in the eighteenth and nineteenth centuries, with particular reference to the British colonies of Demerara, Essequibo and Berbice (formerly British Guiana, now Guyana); the Magna Carta 1215 to the Slavery Abolition Act 1833; the factors which led to the introduction of human rights provisions in English law in the Human Rights Act 1998; and the decision of the House of Lords in A & Others v Secretary of State for the Home Department2 in 2005, relating to the question of admissibility of evidence procured by torture. The thesis of the paper is that English common law was found wanting in connection with the application of fundamental principles of human rights in the United Kingdom and colonies. Lord Mansfield and the other judges who heard the case of Somerset were provided with an excellent opportunity to apply fundamental common law principles of personal security and liberty of the individual to rule that slavery and the slave trade were in breach of the common law and to set a precedent by declaring the liberty of each and every slave who arrived on English shores. Sadly, the judgment failed to live up to the expectations of many of those who had followed the case with avid interest, and it was not until 228 years after that judgment that fundamental principles of human rights became part and parcel of English domestic law, with the introduction of the Human Rights Act 1998 on 2 October 2000

Criminal Law – Let judges fix all life tariffs

Colin Bob-Semple reviews five decisions in English courts that have highlighted the need for reform of the procedure for fixing tariff periods for life prisoners. Article by Colin Bobb-Semple (Senior Lecturer, Inns of Court School of Law) published in Amicus Curiae - Journal of the Institute of Advanced Legal Studies and its Society for Advanced Legal Studies. The Journal is produced by the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies, University of London