The genetic structure of Australian populations of Mycosphaerella musicola suggests restricted gene flow at the continental scale

Mycosphaerello musicolo causes Sigatoka disease of banana and is endemic to Australia. The population genetic structure of M. musicola in Australia was examined by applying single-copy restriction fragment length polymorphism probes to hierarchically sampled populations collected along the Australian cast coast. The 363 isolates studied were from 16 plantations at 12 sites in four different regions, and comprised 11 populations. These populations displayed moderate levels of gene diversity (H = 0.142 to 0.369) and similar levels of genotypic richness and evenness. Populations were dominated by unique genotypes, but isolates sharing the same genotype (putative clones) were detected. Genotype distribution was highly localized within each population, and the majority of putative clones were detected for isolates sampled from different sporodochia in the same lesion or different lesions on a plant. Multilocus gametic disequilibrium tests provided further evidence of a degree of clonality within the populations at the plant scale. A complex pattern of population differentiation was detected for M. musicola in Australia. Populations sampled from plantations outside the two major production areas were genetically very different to all other populations. Differentiation was much lower between populations of the two major production areas, despite their geographic separation of over 1,000 km. These results suggest low gene flow at the continental scale due to limited spore dispersal and the movement of infected plant material.

Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families

Aim To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients. Method Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT). Results A peak of linkage (MLS = 1.35, NPL = 0.91) was shown for marker D16S750, but this was not significant (P = 0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P = 0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype. Conclusion Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups.

Genetic diversity and regional identity in the Australian remnant Nothofagus moorei

Nothofagus moorei (F. Muell.) Krasser has a disjunct and narrow distribution in south-eastern Australian cool temperate rainforest. To assess the conservation-genetic priorities for this species, the genetic diversity of 20 populations sampled from the largest remnant patches at northern and southern distributional extremes, the McPherson and Barrington ranges (a total of 146 individuals), was investigated by using inter simple sequence repeats (ISSR). Regeneration in northern regions of N. moorei has been documented to be predominantly by vegetative means, but our results indicate little evidence of clonality outside the multi-stemmed rings of trees. In addition, genetic diversity was considerably higher in the northern (McPherson, h = 0.1613) than in the southern range (Barrington, h = 0.1159), and genetic differentiation was significantly positively correlated with geographic distance in the former region, but not the latter. Total intraspecific variation was moderate, as measured by Shannon's diversity index, I = 0.2719, and Nei's gene diversity, h = 0.1672, and is considered at the high end of spectrum for estimates of narrow endemic species. An analysis of molecular variation indicated that the majority of genetic variation is partitioned among individuals within population (60%; P < 0.001), rather than among populations within regions (10%; P < 0.001). However, a large and significant component of the measured diversity was partitioned between northern and southern regions (29%; P < 0.001). Several hypotheses are outlined to explain these differences and management implications are discussed. However, given the narrow range, poor dispersal mechanism and restriction to cool temperate rainforest, the continued existence of N. moorei is most threatened by environmental instability and habitat loss resulting from global climate change. In this context the northern regions of the species are most at risk and extinction of such populations would lead to a significant loss of genetic variation for the species as a whole.

Genetic analyses of DSM-IV nicotine withdrawal in adult twins

Background. We examined whether there are genetic influences on nicotine withdrawal. and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from Young adult Australian twins reporting any cigarette use (3026 women. 2553 men: mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%). and Similar in men and women. The exceptions were depressed mood upon withdrawal. which had stronger additive genetic influences in men (53%) compared to worrien (29%). and decreased heart rate. which had low heritability (9%). Although prevalence rates were substantlally lower for DSM-IV nicotine withdrawal syndrome (15-9%), which requires impairment. than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'). qualtity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of it vulnerability to nicotine withdrawal.

Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design

Background. Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD. Method. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models. Results. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD. Conclusions. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

Genetic and environmental influences on extreme personality dispositions in adolescent female twins

Background: The objective was to determine whether the pattern of environmental and genetic influences on deviant personality scores differs from that observed for the normative range of personality, comparing results in adolescent and adult female twins. Methods: A sample of 2,796 female adolescent twins ascertained from birth records provided Junior Eysenck Personality Questionnaire data. The average age of the sample was 17.0 years ( S. D. 2.3). Genetic analyses of continuous and extreme personality scores were conducted. Results were compared for 3,178 adult female twins. Results: Genetic analysis of continuous traits in adolescent female twins were similar to findings in adult female twins, with genetic influences accounting for between 37% and 44% of the variance in Extraversion (Ex), Neuroticism (N), and Social Non-Conformity (SNC), with significant evidence of shared environmental influences (19%) found only for SNC in the adult female twins. Analyses of extreme personality characteristics, defined categorically, in the adolescent data and replicated in the adult female data, yielded estimates for high N and high SNC that deviated substantially (p < .05) from those obtained in the continuous trait analyses, and provided suggestive evidence that shared family environment may play a more important role in determining personality deviance than has been previously found when personality is viewed continuously. However, multiple-threshold models that assumed the same genetic and environmental determinants of both normative range variation and extreme scores gave acceptable fits for each personality dimension. Conclusions: The hypothesis of differences in genetic or environmental factors responsible for N and SNC among female twins with scores in the extreme versus normative ranges was partially supported, but not for Ex.

A possible smoking susceptibility locus on chromosome 11p12: Evidence from sex-limitation linkage analyses in a sample of Australian twin families

Many twin studies have identified sex differences in the influence of genetic and environmental factors on smoking behaviors. We explore the evidence for sex differences for smoking initiation and cigarette consumption in a sample of Australian twin families, and extend these models to incorporate sex differences in linkage analyses for these traits. We further examine the impact of including or excluding non-smokers in genetic analyses of tobacco consumption. Accounting for sex differences improved linkage results in some instances. We identified one region suggestive of linkage on chromosome 11p12. This locus, as well as another region identified on chromosome 6p12, replicates regions identified in previous studies.

Active genetic elements present in the locus of enterocyte effacement in Escherichia coli O26 and their role in mobility

The locus of enterocyte effacement (LEE) is a large multigene chromosomal segment encoding gene products responsible for the generation of attaching and effacing lesions in many diarrheagenic Escherichia coli strains. A recently sequenced LEE harboring a pathogenicity island (PAI) from a Shiga toxin E. coli serotype 026 strain revealed a LEE PAI (designated LEE 026) almost identical to that obtained from a rabbit-specific enteropathogenic 015:H- strain. LEE 026 comprises 59,540 bp and is inserted at 94 min within the mature pheU tRNA locus. The LEE 026 PAI is flanked by two direct repeats of 137 and 136 bp (DR1 and DR2), as well as a gene encoding an integrase belonging to the P4 integrase family. We examined LEE 026 for horizontal gene transfer. By generating mini-LEE plasmids harboring only DR1 or DR2 with or without the integrase-like gene, we devised a simple assay to examine recombination processes between these sequences. Recombination was shown to be integrase dependent in a Delta recA E. coli K-12 strain background. Recombinant plasmids harboring a single direct repeat cloned either with or without the LEE 026 integrase gene were found to insert within the chromosomal pheU locus of E. coli K-12 strains with equal efficiency, suggesting that an endogenous P4-like integrase can substitute for this activity. An integrase with strong homology to the LEE 026 integrase was detected on the K-12 chromosome associated with the leuX tRNA locus at 97 min. Strains deleted for this integrase demonstrated a reduction in the insertion frequency of plasmids harboring only the DR into the pheU locus. These results provide strong evidence that LEE-harboring elements are indeed mobile and suggest that closely related integrases present on the chromosome of E. coli strains contribute to the dynamics of PAI mobility.

Genetic manipulation of blood group carbohydrates alters development and pathfinding of primary sensory axons of the olfactory systems

Primary sensory neurons in the vertebrate olfactory systems are characterised by the differential expression of distinct cell surface carbohydrates. We show here that the histo-blood group H carbohydrate is expressed by primary sensory neurons in both the main and accessory olfactory systems while the blood group A carbohydrate is expressed by a subset of vomeronasal neurons in the developing accessory olfactory system. We have used both loss-of-function and gain-of-function approaches to manipulate expression of these carbohydrates in the olfactory system. In null mutant mice lacking the alpha(1,2)fucosyltransferase FUT1, the absence of blood group H carbohydrate resulted in the delayed maturation of the glomerular layer of the main olfactory bulb. In addition, ubiquitous expression of blood group A on olfactory axons in gain-of-function transgenic mice caused mis-routing of axons in the glomerular layer of the main olfactory bulb and led to exuberant growth of vomeronasal axons in the accessory olfactory bulb. These results provide in vivo evidence for a role of specific cell surface carbohydrates during development of the olfactory nerve pathways. (c) 2006 Elsevier Inc. All rights reserved.

Significant patterns of population genetic structure and limited gene flow in a threatened macropodid marsupial despite continuous habitat in southeast Queensland, Australia

Many endangered species worldwide are found in remnant populations, often within fragmented landscapes. However, when possible, an understanding of the natural extent of population structure and dispersal behaviour of threatened species would assist in their conservation and management. The brush-tailed rock-wallaby (Petrogale penicillata), a once abundant and widespread rock-wallaby species across southeastern Australia, has become nearly extinct across much of the southern part of its range. However, the northern part of the species' range still sustains many small colonies closely distributed across suitable habitat, providing a rare opportunity to investigate the natural population dynamics of a listed threatened species. We used 12 microsatellite markers to investigate genetic diversity, population structure and gene flow among brush-tailed rock-wallaby colonies within and among two valley regions with continuous habitat in southeast Queensland. We documented high and signifcant levels of population genetic structure between rock-wallaby colonies embedded in continuous escarpment habitat and forest. We found a strong and significant pattern of isolation-by-distance among colonies indicating restricted gene flow over a small geographic scale (< 10 km) and conclude that gene flow is more likely limited by intrinsic factors rather than environmental factors. In addition, we provide evidence that genetic diversity was significantly lower in colonies located in a more isolated valley region compared to colonies located in a valley region surrounded by continuous habitat. These findings shed light on the processes that have resulted in the endangered status of rock-wallaby species in Australia and they have strong implications for the conservation and management of both the remaining 'connected' brush-tailed rock-wallaby colonies in the northern parts of the species' range and the remnant endangered populations in the south.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the A phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. in this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Migraine With Aura and Migraine Without Aura Are Not Distinct Entities: Further Evidence From a Large Dutch Population Study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [0CI} .27 -.59), similar to IHS-based migraine diagnosis (h(2) = .49, 95% Cl .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h(2) = .33, 95% Cl .00-.60), but not the LCA-based classification (h(2) = .51, 95% Cl. 23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

Genetic and Cultural Transmission of Smoking Initiation: An Extended Twin Kinship Model

Background Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. Results Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype–environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age × gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. Conclusions This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.

Genetic structure and male-mediated gene flow in the ghost bat (Macroderma gigas)

The Australian ghost bat is a large, opportunistic carnivorous species that has undergone a marked range contraction toward more mesic, tropical sites over the past century. Comparison of mitochondrial DNA (mtDNA) control region sequences and six nuclear microsatellite loci in 217 ghost bats from nine populations across subtropical and tropical Australia revealed strong population subdivision (mtDNA phi(ST) = 0.80; microsatellites URST = 0.337). Low-latitude (tropical) populations had higher heterozygosity and less marked phylogeographic structure and lower subdivision among sites within regions (within Northern Territory [NT] and within North Queensland [NQ]) than did populations at higher latitudes (subtropical sites; central Queensland [CQ]), although sampling of geographically proximal breeding sites is unavoidably restricted for the latter. Gene flow among populations within each of the northern regions appears to be male biased in that the difference in population subdivision for mtDNA and microsatellites (NT phi(ST) = 0.39, URST = 0.02; NQ phi(ST) = 0.60, URST = -0.03) is greater than expected from differences in the effective population size of haploid versus diploid loci. The high level of population subdivision across the range of the ghost bat contrasts with evidence for high gene flow in other chiropteran species and may be due to narrow physiological tolerances and consequent limited availability of roosts for ghost bats, particularly across the subtropical and relatively arid regions. This observation is consistent with the hypothesis that the contraction of the species' range is associated with late Holocene climate change. The extreme isolation among higher-latitude populations may predispose them to additional local extinctions if the processes responsible for the range contraction continue to operate.

The neural correlates of reading impairment in adults with developmental dyslexia:evidence from fMRI between group analyses and an fMRI multiple-case study

The goal of this project was to investigate the neural correlates of reading impairment in dyslexia as hypothesised by the main theories – the phonological deficit, visual magnocellular deficit and cerebellar deficit theories, with emphasis on individual differences. This research took a novel approach by: 1) contrasting the predictions in one sample of participants with dyslexia (DPs); 2) using a multiple-case study (and between-group comparisons) to investigate differences in BOLD between each DP and the controls (CPs); 3) demonstrating a possible relationship between reading impairment and its hypothesised neural correlates by using fMRI and a reading task. The multiple-case study revealed that the neural correlates of reading in dyslexia in all cases are not in agreement with the predictions of a single theory. The results show striking individual differences - even, where the neural correlates of reading in two DPs are consistent with the same theory, the areas can differ. A DP can exhibit under-engagement in an area in word, but not in pseudoword reading and vice versa, demonstrating that underactivation in that area cannot be interpreted as a ‘developmental lesion’. Additional analyses revealed complex results. Within-group analyses between behavioural measures and BOLD showed correlations in the predicted regions, areas outside ROI, and lack of correlations in some predicted areas. Comparisons of subgroups which differed on Orthography Composite supported the MDT, but only for Words. The results suggest that phonological scores are not a sufficient predictor of the under-engagement of phonological areas during reading. DPs and CPs exhibited correlations between Purdue Pegboard Composite and BOLD in cerebellar areas only for Pseudowords. Future research into reading in dyslexia should use a more holistic approach, involving genetic and environmental factors, gene by environment interaction, and comorbidity with other disorders. It is argued that multidisciplinary research, within the multiple-deficit model holds significant promise here.