The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Deforestation and apparent extinctions of endemic forest beetles in Madagascar

Madagascar has lost about half of its forest cover since 1953 with much regional variation, for instance most of the coastal lowland forests have been cleared. We sampled the endemic forest dwelling Helictopleurini dung beetles across Madagascar during 2002–2006. Our samples include 29 of the 51 previously known species for which locality information is available. The most significant factor explaining apparent extinctions (species not collected by us) is forest loss within the historical range of the focal species, suggesting that deforestation has already caused the extinction, or effective extinction, of a large number of insect species with small geographical ranges, typical for many endemic taxa in Madagascar. Currently, roughly 10% of the original forest cover remains. Species–area considerations suggest that this will allow roughly half of the species to persist. Our results are consistent with this prediction.

More-than-human histories and the failure of grand state schemes: sylviculture in the New Forest, England

As James Scott’s Seeing Like a State attests, forests played a central role in the rise of the modern state, specifically as test spaces for evolving methods of managing state resources at a distance, and as the location for grand state schemes. Together, such ambitions necessitated both the elimination of local understandings of forest management – to be replaced by centrally controlled scientific precision – and a narrowing of state vision. Forests thus began to be conflated with trees (and their timber) alone. All other aspects of the forest, both human and non-human, were ignored. Through the lens of the 18th and early 19th century New Forest in southern England, this paper examines the impact of government attempts to shift the focus of state forests from being remnant medieval hunting spaces to spaces of income generation through the creation of vast sylvicultural plantations. This state scheme not only reworked the relationship between the metropole and the provinces – something effected through systematic surveys and novel bureaucratic procedures – but also dramatically impacted upon the biophysical and cultural geographies of the forest. By equating forest space with trees alone, the British state failed to legislate for the actions of both local commoners and non-human others in resisting their schemes. Indeed, subsequent oppositions proved not only the tenacity of commoners in protecting their livelihoods but also the destructive power of non-human actants, specifically rabbits and mice. The paper concludes that grand state schemes necessarily fail due to their own internal illogic: the narrowing of state vision creates blind spots in which human and non-human lives assert their own visions.

Quantitative genetics of preference and performance on chickpeas in the noctuid moth, Helicoverpa armigera

If a novel, resistant host-plant genotype arises in the environment, insect populations utilising that host must be able to overcome that resistance in order that they can maintain their ability to feed on that host. The ability to evolve resistance to host-plant defences depends upon additive genetic variation in larval performance and adult host-choice preference. To investigate the potential of a generalist herbivore to respond to a novel resistant host, we estimated the heritability of larval performance in the noctuid moth, Helicoverpa armigera, on a resistant and a susceptible variety of the chickpea, Cicer arietinum, at two different life stages. Heritability estimates were higher for neonates than for third-instar larvae, suggesting that their ability to establish on plants could be key to the evolution of resistance in this species; however, further information regarding the nature of selection in the field would be required to confirm this prediction. There was no genetic correlation between larval performance and oviposition preference, indicating that female moths do not choose the most suitable plant for their offspring. We also found significant genotype by environment interactions for neonates (but not third-instar larvae), suggesting that the larval response to different plant genotypes is stage-specific in this species.

Parametric and non-parametric estimates of willingness to pay for forest recreation in Northern Ireland: A discrete choice contingent valuation study with follow-ups

In this study we show that forest areas contribute significantly to the estimated benefits from om outdoor recreation in Northern Ireland. Secondly we provide empirical evidence of the gains in the statistical efficiency of both benefit and parameter estimates obtained by analysing follow-up responses with Double Bounded interval data analysis. As these gains are considerable, it is clearly worth considering this method in CVM survey design even when moderately large sample sizes are used. Finally we demonstrate that estimates of means and medians of WTP distributions for access to forest recreation show plausible magnitude, are consistent with previous UK studies, and converge across parametric and non-parametic methods of estimation.

Conservation genetics of Neotropical pollinators revisited: microsatellite analysis suggests that diploid males are rare in orchid bees

Allozyme analyses have suggested that Neotropical orchid bee (Euglossini) pollinators are vulnerable because of putative high frequencies of diploid males, a result of loss of sex allele diversity in small hymenopteran populations with single locus complementary sex determination. Our analysis of 1010 males from 27 species of euglossine bees sampled across the Neotropics at 2-11 polymorphic microsatellite loci revealed only 5 diploid males at an overall frequency of 0.005 (95% CIs 0.002-0.010); errors through genetic non-detection of diploid males were likely small. In contrast to allozyme-based studies, we detected very weak or insignificant population genetic structure, even for a pair of populations >500 km apart, possibly accounting for low diploid male frequencies. Technical flaws in previous allozyme-based analyses have probably led to considerable overestimation of diploid male production in orchid bees. Other factors may have a more immediate impact on population persistence than the genetic load imposed by diploid males on these important Neotropical pollinators.

Decadence in the Forest: Smyth's Der Wald in its Critical Context

Ethel Smyth’s opera, Der Wald, met with mixed reactions at its premiere in Berlin in 1902. Many factors contributed to this, not least, as Smyth herself observed, anti-British sentiment in Germany following the second Boer War. One might have expected that the reception of the opera at its British premiere on 18 July at Covent Garden might have been more positive, but even here critical opinion was divided. Even positive reviews were not free from gender discrimination, and other reviews condemned the opera for being too German or Wagnerian. What was meant by ‘Wagnerian’? This article answers the question in three ways. Firstly, I argue that ‘Wagnerian’ meant not a leitmotif-filled, through-composed work (as distinct from a number opera), but simply a lyrical drama; for British audiences the model for this was Tannhäuser or Lohengrin, not the Ring or Tristan. Secondly, taking this definition on board, I analyse the musical language of the opera, in particular the key structure. The central duet sung by the doomed lovers, Heinrich and Röschen, is in F major, almost the furthest possible distance from the home key of the opera (E major), which characterizes the forest and ‘nature’ in general; by contrast, the next scene, where the Kundry-like Iolanthe attempts to seduce Heinrich (a crucial reversal of the more conventional power relations of the love duet), sees a return to the home key. Thirdly, I set the hermeneutical implications of this reversal in the context of the decadent movement, with which late nineteenth-century Wagnerism was associated, and which, following the conviction of Oscar Wilde in 1895, was discredited. Der Wald thus failed because of its ‘guilt by association’ with an aesthetic that had fallen into disrepute.

Advances in the Genetics of Familial Renal Cancer

We discuss recent advances in the diagnosis and management of renal cell cancer (RCC) given the enhanced molecular genetics knowledge in this area. A number of hereditary renal cancer syndromes have been described, including von Hippel-Lindau disease, Birt-Hogg-Dube syndrome, hereditary leiomyomatosis/RCC syndrome, and hereditary papillary renal cancer. Early molecular diagnosis now facilitates the management and prevention of RCC in families. Recommendations for screening in families are discussed. The Oncologist 2010;15:532-538

Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics

Objectives: Genetic testing for the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 has important implications for the clinical management of people found to carry a mutation. However, genetic testing is expensive and may be associated with adverse psychosocial effects. To provide a cost-efficient and clinically appropriate genetic counselling service, genetic testing should be targeted at those individuals most likely to carry pathogenic mutations. Several algorithms that predict the likelihood of carrying a BRCA1 or a BRCA2 mutation are currently used in clinical practice to identify such individuals.

Breast cancer genetics: Unsolved questions and open perspectives in an expanding clinical practice

Breast cancer is the most common cause of cancer death in the United Kingdom, with a lifetime risk of one in nine in women. Only 5-10% of all cancers is thought to be due to strongly penetrant inherited predisposing genes, such as BRCA1 and BRCA2. However, other less penetrant genes, including some autosomal recessive genes, are likely to be of etiological importance in other families. This review addresses the current knowledge of breast cancer susceptibility genes and explores the possibilities for future developments. Features of tumor pathology, prognosis, and the scope for targeted treatments in mutation carriers are discussed, and the management of known carriers and those at increased risk for developing breast cancer are evaluated. Genetic testing for cancer susceptibility may become widely available in the future, and has important ethical and management implications. (C) 2004 Wiley-Liss, Inc.