Myocardial bridging: what have we learned in the past and will new diagnostic modalities provide new insights?

The clinical significance of myocardial bridging has been a subject of discussion and controversy since the introduction of coronary arteriography (CAG) in the early 1960s. More recently computed tomography coronary angiography (CTCA) has made it possible to visualise the overlying muscular bands and appears to have a higher sensitivity for detecting myocardial bridging than CAG. Combining CTCA with invasive techniques such as CAG should make it possible to improve our understanding of the pathophysiology of myocardial bridging and to provide answers to hitherto unresolved questions. This paper critically reviews the outcomes of previous studies and defines remaining questions that should be answered to optimise the management of the presumably fast growing number of patients in whom a diagnosis of myocardial bridging has been made.     

Translational behaviour‐genetic studies of alcohol: are we there yet?

In biomedical research, one key stage of translating basic science knowledge to clinical practice is the reconciliation of phenotypes employed for laboratory animal studies with those important for the clinical condition. Alcohol dependence (AD) is a prototypic complex genetic trait. There is a long history of behaviour-genetic studies of AD in both human subjects and various genetic animal models. This review assesses the state of the art in our understanding of the genetic contributions to AD. In particular, it primarily focuses on the phenotypes studied in mouse genetic animal models, comparing them to the aspects of the human condition they are intended to target. It identifies several features of AD where genetic animal models have been particularly useful, and tries to identify understudied areas where there is good promise for further genetic animal model work.     

When can noninvasive samples provide sufficient information in conservation genetics studies?

Noninvasive sampling, of faeces and hair for example, has enabled many genetic studies of wildlife populations. However, two prevailing problems common to these studies are small sample sizes and high genotyping errors. The first problem stems from the difficulty in collecting noninvasive samples, particularly from populations of rare or elusive species, and the second is caused by the low quantity and quality of DNA extracted from a noninvasive sample. A common question is therefore whether noninvasive sampling provides sufficient information for the analyses commonly conducted in conservation genetics studies. Here, we conducted a simulation study to investigate the effect of small sample sizes and genotyping errors on the precision and accuracy of the most commonly estimated genetic parameters. Our results indicate that small sample sizes cause little bias in measures of expected heterozygosity, pairwise F_ST and population structure, but a large downward bias in estimates of allelic diversity. Allelic dropouts and false alleles had a much smaller effect than missing data, which effectively reduces sample size further. Overall, reasonable estimates of genetic variation and population subdivision are obtainable from noninvasive samples as long as error rates are kept below a frequency of 0.2. Similarly, unbiased estimates of population clustering can be made with genotyping error rates below 0.5 when the populations are highly differentiated. These results provide a useful guide for researchers faced with studying the conservation genetics of small, endangered populations from noninvasive samples.     

Associations between anticipated reactions to genetic test results and interest in genetic testing: will self-selection reduce the potential for harm?

The proliferation of genetic susceptibility tests for complex diseases away from clinic settings increases the potential for harm. This study assessed whether people are likely to self-select themselves into or out of genetic testing depending on whether they believe they could cope with the results. Associations between anticipated reactions to adverse genetic test results and interest in taking genetic tests for cancer and heart disease were examined in a community sample of English adults (n = 1,024). Interest in genetic testing overall was 78% for cancer risk and 80% for heart disease risk. As predicted, there were differences by anticipated reactions. People who anticipated regret about having taken a genetic test for cancer risk expressed lower interest than those who did not anticipate regret (46% vs. 89%), and people who anticipated being glad to know of increased risk status (i.e., reduced uncertainty) were more interested than those who did not look forward to reduced uncertainty (91% vs. 22%). Patterns were similar for heart disease ("regret" 66% vs. 87%; "reduced uncertainty" 87% vs. 38%). The potential for harm from future genetic susceptibility tests may be less than feared if people who anticipate adverse reactions self-select themselves out of testing. However, given that a significant proportion of people who anticipated adverse reactions also expressed interest in testing, there is still a concern about safety. It remains to be seen whether the same patterns emerge in studies that actually offer genetic tests for common gene variants in community settings.     

Independent methods for evolutionary genetic dating provide insights into Y-chromosomal STR mutation rates confirming data from direct father–son transmissions

Five datasets consisting of samples jointly typed for Y-chromosomal Unique Event Polymorphism (UEP) and simple tandem repeat (STR) markers were re-examined with independent methods for dating the different UEP-defined lineages. We report on the results obtained with an original program which performs comparative dating (BARCODE) in comparison with coalescent analyses performed with BATWING under various prior conditions. For the first time these are equalized across datasets. We also report on the results concerning STR mutability as obtained with both methods. The dating results for the entire series of sub-haplogroups are highly correlated. Within coalescent analyses, dating-estimates under a wide range of priors tend to converge. As to STR mutation rates the main findings are: (1) large variations among loci within the same dataset with both methods, also when the same prior was used for all loci; (2) figures in most cases above 1×10⁻³ and often above 2×10⁻³; (3) a few loci that mutate differently across studies. These results closely match those obtained from direct observation of father–son transmissions. Overall, this work supports the use of genetic dating procedures that take into account the complexity of the phenomenon, with a repertoire of priors tailored on the particular dataset.     

Root patterning: does auxin provide positional cues?

Patterning of Arabidopsis roots is mediated by cell-cell interactions, information flowing from differentiated to immature cells. The plant growth regulator auxin has now been shown to be involved in organizing the distal end of the root apex, including the extent and pattern of cell division programs and specification of cell identity.     

Pharmacogenomics: will the promise be fulfilled?

Tools such as genome resequencing and genome-wide association studies have recently been used to uncover a number of variants that affect drug toxicity and efficacy, as well as potential drug targets. But how much closer are we to incorporating pharmacogenomics into routine clinical practice? Five experts discuss how far we have come, and highlight the technological, informatics, educational and practical obstacles that stand in the way of realizing genome-driven medicine.     

Do extra‐pair paternities provide genetic benefits for female blue tits Parus caeruleus?

A large body of theories on extra-pair paternity (EPP) in birds has proposed four main "genetic" hypotheses to explain this behaviour: the "good genes" hypothesis, the genetic diversity hypothesis, the genetic compatibility hypothesis and the fertility insurance hypothesis. Empirical tests have been scarce, mainly because high sample sizes are difficult to collect. We have tested these hypotheses in three Mediterranean populations of blue tits Parus caeruleus in which 50–68% of the broods contained extra-pair young. Results showed that the distribution of extra-pair young among broods was not random, and that survival to fledging of extra-pair young was higher than that of their within-pair sibs. These results support the idea of genetic effects benefiting extra-pair young. However, comparison of cuckolded and cuckolding males showed no significant difference in their body size, age, survival or relatedness with their paired females, and offspring morphometrics did not differ between extra-pair and within-pair young. We conclude that none of the genetic hypotheses can explain fully the high level of extra-pair paternity, at least in our populations of Mediterranean blue tits. We suggest that direct ecological benefits of EPP for females should be tested more often in correlative as well as experimental approaches.     

Mitochondrial kinases in Parkinson’s disease: Converging insights from neurotoxin and genetic models

Alterations in mitochondrial biology have long been implicated in neurotoxin, and more recently, genetic models of parkinsonian neurodegeneration. In particular, kinase regulation of mitochondrial dynamics and turnover are emerging as central mechanisms at the convergence of neurotoxin, environmental and genetic approaches to studying Parkinson’s disease (PD). Kinases that localize to mitochondria during neuronal injury include mitogen activated protein kinases (MAPK) such as extracellular signal regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK), protein kinase B/Akt, and PTEN-induced kinase 1 (PINK1). Although site(s) of action within mitochondria and specific kinase targets are still unclear, these signaling pathways regulate mitochondrial respiration, transport, fission–fusion, calcium buffering, reactive oxygen species (ROS) production, mitochondrial autophagy and apoptotic cell death. In this review, we summarize accelerating experimental evidence gathered over the last decade that implicate a central role for kinase signaling at the mitochondrion in Parkinson’s and related neurodegenerative disorders. Interactions involving α-synuclein, leucine rich repeat kinase 2 (LRRK2), DJ-1 and Parkin are discussed. Converging mechanisms from different model systems support the concept of common pathways in parkinsonian neurodegeneration that may be amenable to future therapeutic interventions.     

Can ribs and septa provide an alternative standard for age in ammonite ontogenetic studies?

In ammonites, the time between two successive septal secretions is assumed to be almost stable during growth within homogeneous sets with regard to phylogeny and morphology. The number of septa (included in the adult phragmocone) is proposed as an alternative standard for age. At each moment of growth, the rate of shell secretion can be directly estimated by the measure of shell length between two septa. Equivalent results are obtained for ribs whose formation is also dependent on an almost stable rhythmical process. Results obtained from septa and size used as age standards are compared in the example of Liparoceratidae-Amaltheidae evolution. The two standards provide estimations of age which diverge from more than 1 to 2. For example, some small species previously seen as progenetic are now classified as dwarfed. These results emphasize the risk of using size as the only standard of age. Alternative standards not only in ammonites but also in other animal groups should be investigated.     

Developmental neurobiology: A genetic Cheshire cat?

In the wake of evidence that essential neurogenic processes might involve aspects of DNA rearrangement, recent discoveries about the unusual arrangement of genes encoding neuronal adhesion molecules known as protocadherins are very intriguing. But is this just a coincidence?     

Agyria — pachygyria and Miller-Dieker syndrome: clinical,genetic and chromosome studies

Summary Twelve cases of lissencephaly are reported. A high resolution chromosome study was performed on each in order to detect small chromosomal anomalies, undetectable with routine techniques. Only one case was shown to have an unbalanced karyotype with a microdeletion of the short arm of chromosome 17(del 17p). This child also had symptoms of the Miller-Dieker syndrome, consisting of lissencephaly, characteristic facies, pre- and post-natal growth retardation and other birth defects. As proposed by Dobyns, it seems justifiable to classify lissencephalies into four different groups, according to other clinical manifestations and results of chromosome studies.     

Integrating genetic information into plant breeding programmes: how will we produce varieties from molecular variation,using bioinformatics?

The development of new varieties of crop plants is ongoing for plant breeders and progress since the Green Revolution has been steady, if not dramatic. With the recent sequencing of Arabidopsis thaliana and of rice the development of both physical and informational resources has entered a new phase. This paper examines the state of plant bioinformatics as it is now and as it is likely to develop in the future. It also looks rather further forward to what crop scientists might want from bioinformatics, before examining the likely physiological targets for sustainability traits and the prospects for their improvement in wheat. Wheat is taken as the focus crop because it is potentially one of the most dif. Cult to work with in molecular terms, both because of its large hexaploid genome size and because of its considerable genetic distance from the most information rich plant species, Arabidopsis. Finally, we examine how these tools might be used to track down the underlying genes controlling sustainability traits and how these may then be exploited in plant breeding programmes using marker‐ assisted selection.