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.

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.

Cognitive modelling and the behaviour genetics of reading

While it is well known that reading is highly heritable, less has been understood about the bases of these genetic influences. In this paper, we review the research that we have been conducting in recent years to examine genetic and environmental influences on the particular reading processes specified in the dual-route cognitive model of reading. We argue that a detailed understanding of the role of genetic factors in reading acquisition requires the delineation and measurement of precise phenotypes, derived from well-articulated models of the reading process. We report evidence for independent genetic influences on the lexical and nonlexical reading processes represented in the dual-route model, based on studies of children with particular subtypes of dyslexia, and on univariate and multivariate genetic modelling of reading performance in the normally reading population.

Modelling pre-clearing vegetation distribution using GIS-integrated statistical, ecological and data models: A case study from the wet tropics of Northeastern Australia

Traditional vegetation mapping methods use high cost, labour-intensive aerial photography interpretation. This approach can be subjective and is limited by factors such as the extent of remnant vegetation, and the differing scale and quality of aerial photography over time. An alternative approach is proposed which integrates a data model, a statistical model and an ecological model using sophisticated Geographic Information Systems (GIS) techniques and rule-based systems to support fine-scale vegetation community modelling. This approach is based on a more realistic representation of vegetation patterns with transitional gradients from one vegetation community to another. Arbitrary, though often unrealistic, sharp boundaries can be imposed on the model by the application of statistical methods. This GIS-integrated multivariate approach is applied to the problem of vegetation mapping in the complex vegetation communities of the Innisfail Lowlands in the Wet Tropics bioregion of Northeastern Australia. The paper presents the full cycle of this vegetation modelling approach including sampling sites, variable selection, model selection, model implementation, internal model assessment, model prediction assessments, models integration of discrete vegetation community models to generate a composite pre-clearing vegetation map, independent data set model validation and model prediction's scale assessments. An accurate pre-clearing vegetation map of the Innisfail Lowlands was generated (0.83r(2)) through GIS integration of 28 separate statistical models. This modelling approach has good potential for wider application, including provision of. vital information for conservation planning and management; a scientific basis for rehabilitation of disturbed and cleared areas; a viable method for the production of adequate vegetation maps for conservation and forestry planning of poorly-studied areas. (c) 2006 Elsevier B.V. All rights reserved.

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.

Molecular phylogeny and biogeography of the dung beetle genus Temnoplectron Westwood (Scarabaeidae: Scarabaeinae) from Australia’s wet tropics

The landscape of the Australian Wet Tropics can be described as islands of montane rainforest Surrounded by warmer or more xeric habitats. Historical glaciation cycles have caused expansion and contraction of these rainforest islands leading to consistent patterns of genetic divergence within species of vertebrates. To explore whether this dynamic history has promoted speciation in endemic and diverse groups Of insects, we used a combination of mtDNA sequencing and morphological characters to estimate relationships and the tempo of divergence among Australian representatives of the dung beetle genus Temnoplectron. This phylogenetic hypothesis shares a number of well-supported clades with a previously published phylogenetic hypothesis based on morphological data. though statistical support for several nodes is weak. Sister species relationships well-supported in both tree topologies. and a tree obtained by combining the two data sets. suggest that speciation has mostly been allopatric. We identify a number of speciation barriers, which coincide with phylogeographic breaks found in vertebrate species. Large sequence divergences between species emphasize that speciation events are ancient (pre-Pleistocene). The flightless, rainforest species appear to have speciated rapidly. but also in the distant past. (C) 2003 Elsevier Inc. All rights reserved.

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.

Analysis of Melanoma Onset: Assessing Familial Aggregation by Using Estimating Equations and Fitting Variance Components via Bayesian Random Effects Models

We investigate whether relative contributions of genetic and shared environmental factors are associated with an increased risk in melanoma. Data from the Queensland Familial Melanoma Project comprising 15,907 subjects arising from 1912 families were analyzed to estimate the additive genetic, common and unique environmental contributions to variation in the age at onset of melanoma. Two complementary approaches for analyzing correlated time-to-onset family data were considered: the generalized estimating equations (GEE) method in which one can estimate relationship-specific dependence simultaneously with regression coefficients that describe the average population response to changing covariates; and a subject-specific Bayesian mixed model in which heterogeneity in regression parameters is explicitly modeled and the different components of variation may be estimated directly. The proportional hazards and Weibull models were utilized, as both produce natural frameworks for estimating relative risks while adjusting for simultaneous effects of other covariates. A simple Markov Chain Monte Carlo method for covariate imputation of missing data was used and the actual implementation of the Bayesian model was based on Gibbs sampling using the free ware package BUGS. In addition, we also used a Bayesian model to investigate the relative contribution of genetic and environmental effects on the expression of naevi and freckles, which are known risk factors for melanoma.

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.

Genetic analysis of complex demographic scenarios: Spatially expanding populations of the cane toad, Bufo marinus

Inferring the spatial expansion dynamics of invading species from molecular data is notoriously difficult due to the complexity of the processes involved. For these demographic scenarios, genetic data obtained from highly variable markers may be profitably combined with specific sampling schemes and information from other sources using a Bayesian approach. The geographic range of the introduced toad Bufo marinus is still expanding in eastern and northern Australia, in each case from isolates established around 1960. A large amount of demographic and historical information is available on both expansion areas. In each area, samples were collected along a transect representing populations of different ages and genotyped at 10 microsatellite loci. Five demographic models of expansion, differing in the dispersal pattern for migrants and founders and in the number of founders, were considered. Because the demographic history is complex, we used an approximate Bayesian method, based on a rejection-regression algorithm. to formally test the relative likelihoods of the five models of expansion and to infer demographic parameters. A stepwise migration-foundation model with founder events was statistically better supported than other four models in both expansion areas. Posterior distributions supported different dynamics of expansion in the studied areas. Populations in the eastern expansion area have a lower stable effective population size and have been founded by a smaller number of individuals than those in the northern expansion area. Once demographically stabilized, populations exchange a substantial number of effective migrants per generation in both expansion areas, and such exchanges are larger in northern than in eastern Australia. The effective number of migrants appears to be considerably lower than that of founders in both expansion areas. We found our inferences to be relatively robust to various assumptions on marker. demographic, and historical features. The method presented here is the only robust, model-based method available so far, which allows inferring complex population dynamics over a short time scale. It also provides the basis for investigating the interplay between population dynamics, drift, and selection in invasive species.

RNA regulation: a new genetics?

Do non-coding RNAs that are derived from the introns and exons of protein-coding and non-protein-coding genes represent a fundamental advance in the genetic operating system of higher organisms? Recent evidence from comparative genomics and molecular genetics indicates that this might be the case. If so, there will be profound consequences for our understanding of the genetics of these organisms, and in particular how the trajectories of differentiation and development and the differences among individuals and species are genomically programmed. But how might this hypothesis be tested?

Advantage of single-trial models for response to selection in wheat breeding multi-environment trials

An investigation was conducted to evaluate the impact of experimental designs and spatial analyses (single-trial models) of the response to selection for grain yield in the northern grains region of Australia (Queensland and northern New South Wales). Two sets of multi-environment experiments were considered. One set, based on 33 trials conducted from 1994 to 1996, was used to represent the testing system of the wheat breeding program and is referred to as the multi-environment trial (MET). The second set, based on 47 trials conducted from 1986 to 1993, sampled a more diverse set of years and management regimes and was used to represent the target population of environments (TPE). There were 18 genotypes in common between the MET and TPE sets of trials. From indirect selection theory, the phenotypic correlation coefficient between the MET and TPE single-trial adjusted genotype means [r(p(MT))] was used to determine the effect of the single-trial model on the expected indirect response to selection for grain yield in the TPE based on selection in the MET. Five single-trial models were considered: randomised complete block (RCB), incomplete block (IB), spatial analysis (SS), spatial analysis with a measurement error (SSM) and a combination of spatial analysis and experimental design information to identify the preferred (PF) model. Bootstrap-resampling methodology was used to construct multiple MET data sets, ranging in size from 2 to 20 environments per MET sample. The size and environmental composition of the MET and the single-trial model influenced the r(p(MT)). On average, the PF model resulted in a higher r(p(MT)) than the IB, SS and SSM models, which were in turn superior to the RCB model for MET sizes based on fewer than ten environments. For METs based on ten or more environments, the r(p(MT)) was similar for all single-trial models.

Gene-flow between populations of cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) is highly variable between years

Both large and small scale migrations of Helicoverpa armigera Hübner in Australia were investigated using AMOVA analysis and genetic assignment tests. Five microsatellite loci were screened across 3142 individuals from 16 localities in eight major cotton and grain growing regions within Australia, over a 38-month period (November 1999 to January 2003). From November 1999 to March 2001 relatively low levels of migration were characterized between growing regions. Substantially higher than average gene-flow rates and limited differentiation between cropping regions characterized the period from April 2001 to March 2002. A reduced migration rate in the year from April 2002 to March 2003 resulted in significant genetic structuring between cropping regions. This differentiation was established within two or three generations. Genetic drift alone is unlikely to drive genetic differentiation over such a small number of generations, unless it is accompanied by extreme bottlenecks and/or selection. Helicoverpa armigera in Australia demonstrated isolation by distance, so immigration into cropping regions is more likely to come from nearby regions than from afar. This effect was most pronounced in years with limited migration. However, there is evidence of long distance dispersal events in periods of high migration (April 2001-March 2002). The implications of highly variable migration patterns for resistance management are considered.