Allozyme electrophoresis still represents a powerful technique in the management of coral reefs

Understanding genetic variability and gene flow between populations of scleractinian corals separated by one to several hundred kilometers is crucially important as we head into a century of climate change in which an understanding of the connectivity of populations is a critically important question in management. Genetic methods that directly use molecular variance in the DNA should offer greater precision in detecting differences among individuals and populations than the more traditional allozyme electrophoresis. However, this paper highlights the point that the limited number of DNA markers that have been identified for scleractinian coral genetic studies do not necessarily offer greater precision than that offered by allozymes. In fact, at present allozyme electrophoresis yields greater information than the eight different DNA markers used in this study. Given the relative ease of use of allozymes and the wealth of comparable data sets from numerous previously published studies, allozyme electrophoresis should not be dismissed for population structure and connectivity studies on coral reefs. While continued effort should be placed into searching for new DNA markers, until a more sensitive DNA marker becomes available for scleractinian corals, allozyme electrophoresis remains a powerful and relevant technique for understanding the connectivity of coral population studies.

Genetics and genomics of osteoclast differentiation: Integrating cell signaling pathways and gene networks

The regulation of osteoclast differentiation in the bone microenvironment is critical for normal bone remodeling, as well as for various human bone diseases. Over the last decade, our knowledge of how osteoclast differentiation occurs has progressed rapidly. We highlight some of the major advances in understanding how cell signaling and transcription are integrated to direct the differentiation of this cell type. These studies used genetic, molecular, and biochemical approaches. Additionally, we summarize data obtained from studies of osteoclast differentiation that used the functional genomic approach of global gene profiling applied to osteoclast differentiation. This genomic data confirms results from studies using the classical experimental approaches and also may suggest new modes by which osteoclast differentiation and function can be modulated. Two conclusions that emerge are that osteoclast differentiation depends on a combination of fairly ubiquitously expressed transcription factors rather than unique osteoclast factors, and that the overlay of cell signaling pathways on this set of transcription factors provides a powerful mechanism to fine tune the differentiation program in response to the local bone microenvironment.

Studying phenotypic evolution using multivariate quantitative genetics

Quantitative genetics provides a powerful framework for studying phenotypic evolution and the evolution of adaptive genetic variation. Central to the approach is G, the matrix of additive genetic variances and covariances. G summarizes the genetic basis of the traits and can be used to predict the phenotypic response to multivariate selection or to drift. Recent analytical and computational advances have improved both the power and the accessibility of the necessary multivariate statistics. It is now possible to study the relationships between G and other evolutionary parameters, such as those describing the mutational input, the shape and orientation of the adaptive landscape, and the phenotypic divergence among populations. At the same time, we are moving towards a greater understanding of how the genetic variation summarized by G evolves. Computer simulations of the evolution of G, innovations in matrix comparison methods, and rapid development of powerful molecular genetic tools have all opened the way for dissecting the interaction between allelic variation and evolutionary process. Here I discuss some current uses of G, problems with the application of these approaches, and identify avenues for future research.

Teaching principles of genetics through SNP analysis

An understanding of inheritance requires comprehension of genetic processes at all levels, from molecules to populations. Frequently genetics courses are separated into molecular and organismal genetics and students may fail to see the relationships between them. This is particularly true with human genetics, because of the difficulties in designing experimental approaches which are consistent with ethical restrictions, student abilities and background knowledge, and available time and materials. During 2005 we used analysis of single nucleotide polymorphisms (SNPs) in two genetic regions to enhance student learning and provide a practical experience in human genetics. Students scanned databases to discover SNPs in a gene of interest, used software to design PCR primers and a restriction enzyme based assay for the alleles, and carried out an analysis of the SNP on anonymous individual and family DNAs. The project occupied eight to ten hours per week for one semester, with some time spent in the laboratory and some spent in database searching, reading and writing the report. In completing their projects, students acquired a knowledge of Mendel’s first law (through looking at inheritance patterns), Mendel’s second law and the exceptions (the concepts of linkage and linkage disequilibrium), DNA structure (primer design and restriction enzyme analysis) and function (SNPs in coding and non-coding regions), population genetics and the statistical analysis of allele frequencies, genomics, bioinformatics and the ethical issues associated with the use of human samples. They also developed skills in presentation of results by publication and conference participation. Deficiencies in their understanding (for example of inheritance patterns, gene structure, statistical approaches and report writing) were detected and guidance given during the project. SNP analysis was found to be a powerful approach to enhance and integrate student understanding of genetic concepts.

Psychiatric genetics in Australia

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery. (C) 2003 Lippincott Williams Wilkins.

The genetics of alcohol intake and of alcohol dependence

Background: Because alcohol has multiple dose-dependent consequences, it is important to understand the causes of individual variation in the amount of alcohol used. The aims of this study were to assess the long-term repeatability and genetic or environmental causes of variation in alcohol intake and to estimate the degree of overlap with causes of susceptibility to alcohol dependence. Methods: Data were used from three studies conducted between 1980 and 1995 on volunteer adult male and female Australian twin subjects. In each study, alcohol intake was reported both as quantity X frequency and as past-week data. Repeatability was calculated as correlations between occasions and between measures, and the effects of genes and environment were estimated by multivariate model fitting to the twin pair repeated measures of alcohol use. Relationships between mean alcohol use and the lifetime history of DSM-III-R alcohol dependence were tested by bivariate model fitting. Results: Repeatability of the alcohol intake measures was between 0.54 and 0.85, with the highest repeatability between measures within study and the lowest repeatability between the first and last studies. Reported alcohol consumption was mainly affected by genetic factors affecting all times of study and by nonshared environmental factors (including measurement error) unique to each time of study. Genes that affect alcohol intake do affect alcohol dependence, but genetic effects unique to dependence are also significant; environmental effects are largely unique to either intake and dependence. Conclusions: Nearly all the repeatable component of variation in alcohol intake is due to genetic effects. Genes affecting intake also affect dependence risk, but there are other genes that affect dependence alone. Studies aiming to identify genes that affect alcohol use disorders need to test loci and candidate genes against both phenotypes.

The epidemiology and genetics of smoking initiation and persistence: Crosscultural comparisons of twin study results

We examined whether there are crosscultural differences in the magnitude of genetic and environmental contributions to risk of becoming a regular smoker and of persistence in smoking in men and women. Standard methods of epidemiologic and genetic analysis were applied to questionnaire data on history of cigarette use obtained from large samples of male and female like-sex twins from three different countries: Australia (N = 2284 pairs), Sweden (N = 8651 pairs), and Finland (N = 10,948 pairs). Samples were subdivided into three age groups (AG), 18-25 years, 26-35 years, and 36-46 years of age. The magnitude of genetic influence for lifetime smoking was found to be consistent across country and AG for women (46%) and men (57%), and estimates of the contribution from environmental influences shared by twin and co-twin could be equated across all countries by AG for the women (from youngest to oldest AG: 45%, 35%, and 26%), but not for men, with separate estimates obtained for the Scandinavian (33%, 29%, and 19%) and the Australian men (26%, 9%, and 11 %). There was no evidence for an important role for shared environmental influences on persistent smoking, and the genetic contribution was found to be consistent in magnitude in men and women, and the same across country and AG (52%). There are strong genetic influences on smoking behavior, and that risk of becoming a smoker (but not persistence in smoking) may be modified by experiences shared by twins that differ by AG and, at least for men, cultural background.

Gene-expression profiling reveals distinct expression patterns for classic versus variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to pro. le 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Interindividual variation of isolated muscle performance and fibre-type composition in the toad Bufo viridus

Interindividual analyses of physiological performance represent one of the most powerful tools for identifying functional positive and negative linkages between various performance traits. In this study we investigated functional linkages in the whole-gastrocnemius performance of juvenile Bufo viridis by examining interindividual variation in in vitro muscle performance and muscle fibre-type composition. We used the work-loop technique to investigate the maximum in vitro power output and fatigue resistance of the gastrocnemius muscle during repeated sets of three cycles at the cycle frequency of 5 Hz, simulating an intermittent style of locomotion. We found several significant correlations between different measures of in vitro muscle performance, including a negative correlation between maximum net power output and fatigue resistance of power, indicating functional trade-offs between these performance traits. We also investigated the extent of individual variation in the proportions of different fibre types, and tested for correlations between individual variation in muscle fibre-type composition and the previously measured isolated muscle performance. Fast glycolytic fibres represented 84.0+/-3.4% of the muscle, while the combined slow oxidative and fast oxidative-glycolytic fibres represented 16+/-3.4%. We found no significant correlations between measures of in vitro muscle performance and the proportion of different fibre types in the gastrocnemius muscle. However, despite this lack of correlation between whole-muscle performance and muscle fibre-type composition data, we suggest the functional linkages detected between different measures of in vitro muscular performance have important ecological and evolutionary consequences.

Major quantitative trait locus for eosinophil count is located on chromosome 2q

Background: Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs. 1 Objective: To identify QTLs responsible for variation in eosinophil count in adolescent twins. Methods: We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome. Results: We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds = 4.6; P = .000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds = 1.0; P = .016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22. Conclusion: A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.

Multivariate quantitative genetics and the Lek Paradox: Genetic variance in male sexually selected traits of Drosophila serrata under field control

Single male sexually selected traits have been found to exhibit substantial genetic variance, even though natural and sexual selection are predicted to deplete genetic variance in these traits. We tested whether genetic variance in multiple male display traits of Drosophila serrata was maintained under field conditions. A breeding design involving 300 field-reared males and their laboratory-reared offspring allowed the estimation of the genetic variance-covariance matrix for six male cuticular hydrocarbons (CHCs) under field conditions. Despite individual CHCs displaying substantial genetic variance under field conditions, the vast majority of genetic variance in CHCs was not closely associated with the direction of sexual selection measured on field phenotypes. Relative concentrations of three CHCs correlated positively with body size in the field, but not under laboratory conditions, suggesting condition-dependent expression of CHCs under field conditions. Therefore condition dependence may not maintain genetic variance in preferred combinations of male CHCs under field conditions, suggesting that the large mutational target supplied by the evolution of condition dependence may not provide a solution to the lek paradox in this species. Sustained sexual selection may be adequate to deplete genetic variance in the direction of selection, perhaps as a consequence of the low rate of favorable mutations expected in multiple trait systems.

Bi-sensory, striped representations: comparative insights from owl and platypus

Bi-sensory striped arrays are described in owl and platypus that share some similarities with the other variant of bi-sensory striped array found in primate and carnivore striate cortex: ocular dominance columns. Like ocular dominance columns, the owl and platypus striped systems each involve two different topographic arrays that are cut into parallel stripes, and interdigitated, so that higher-order neurons can integrate across both arrays. Unlike ocular dominance stripes, which have a separate array for each eye, the striped array in the middle third of the owl tectum has a separate array for each cerebral hemisphere. Binocular neurons send outputs from both hemispheres to the striped array where they are segregated into parallel stripes according to hemisphere of origin. In platypus primary somatosensory cortex (SI), the two arrays of interdigitated stripes are derived from separate sensory systems in the bill, 40,000 electroreceptors and 60,000 mechanoreceptors. The stripes in platypus SI cortex produce bimodal electrosensory-mechanosensory neurons with specificity for the time-of-arrival difference between the two systems. This thunder-and-lightning system would allow the platypus to estimate the distance of the prey using time disparities generated at the bill between the earlier electrical wave and the later mechanical wave caused by the motion of benthic prey. The functional significance of parallel, striped arrays is not clear, even for the highly-studied ocular dominance system, but a general strategy is proposed here that is based on the detection of temporal disparities between the two arrays that can be used to estimate distance. (C) 2004 Elsevier Ltd. All rights reserved.