QUT Library advances the use of open public tools to navigate genetic inventions and builds research networks

Many emerging economies are dangling the patent system to stimulate bio-technological innovations with the ultimate premise that these will improve their economic and social growth. The patent system mandates full disclosure of the patented invention in exchange of a temporary exclusive patent right. Recently, however, patent offices have fallen short of complying with such a mandate, especially for genetic inventions. Most patent offices provide only static information about disclosed patent sequences and even some do not keep track of the sequence listing data in their own database. The successful partnership of QUT Library and Cambia exemplifies advocacy in Open Access, Open Innovation and User Participation. The library extends its services to various departments within the university, builds and encourages research networks to complement skills needed to make a contribution in the real world.

Whole-genome sequencing reveals untapped genetic potential in Africa’s indigenous cereal crop sorghum

Sorghum is a food and feed cereal crop adapted to heat and drought and a staple for 500 million of the world’s poorest people. Its small diploid genome and phenotypic diversity make it an ideal C4 grass model as a complement to C3 rice. Here we present high coverage (16–45 × ) resequenced genomes of 44 sorghum lines representing the primary gene pool and spanning dimensions of geographic origin, end-use and taxonomic group. We also report the first resequenced genome of S. propinquum, identifying 8 M high-quality SNPs, 1.9 M indels and specific gene loss and gain events in S. bicolor. We observe strong racial structure and a complex domestication history involving at least two distinct domestication events. These assembled genomes enable the leveraging of existing cereal functional genomics data against the novel diversity available in sorghum, providing an unmatched resource for the genetic improvement of sorghum and other grass species.

Genetic analysis of GRIA2 and GRIA4 genes in migraine

Background Migraine is a brain disorder affecting ∼12% of the Caucasian population. Genes involved in neurological, vascular, and hormonal pathways have all been implicated in predisposing individuals to developing migraine. The migraineur presents with disabling head pain and varying symptoms of nausea, emesis, photophobia, phonophobia, and occasionally visual sensory disturbances. Biochemical and genetic studies have demonstrated dysfunction of neurotransmitters: serotonin, dopamine, and glutamate in migraine susceptibility. Glutamate mediates the transmission of excitatory signals in the mammalian central nervous system that affect normal brain function including cognition, memory and learning. The aim of this study was to investigate polymorphisms in the GRIA2 and GRIA4 genes, which encode subunits of the ionotropic AMPA receptor for association in an Australian Caucasian population. Methods Genotypes for each polymorphism were determined using high resolution melt analysis and the RFLP method. Results Statistical analysis showed no association between migraine and the GRIA2 and GRIA4 polymorphisms investigated. Conclusions Although the results of this study showed no significant association between the tested GRIA gene variants and migraine in our Australian Caucasian population further investigation of other components of the glutamatergic system may help to elucidate if there is a relationship between glutamatergic dysfunction and migraine.

Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect on breast cancer risk

Breast cancer is the cancer that most commonly affects women worldwide. This type of cancer is genetically complex, but is strongly linked to steroid hormone signalling systems. Because microRNAs act as translational regulators of multiple genes, including the steroid nuclear receptors, single nucleotide polymorphisms (SNPs) in microRNAs genes can have potentially wide-ranging influences on breast cancer development. Thus, this study was conducted to investigate the relationships between six SNPs (rs6977848, rs199981120, rs185641358, rs113054794, rs66461782, and rs12940701) located in four miRNA genes predicted to target the estrogen receptor (miR-148a, miR-221, miR-186, and miR-152) and breast cancer risk in Caucasian Australian women. By using high resolution melt analysis (HRM) and polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), 487 samples including 225 controls and 262 cases were genotyped. Analysis of their genotype and allele frequencies indicated that the differences between case and control populations was not significant for rs6977848, rs66461782, and rs12940701 because their p-values are 0.81, 0.93, 0.1 which are all above the threshold value (p=0.05). Our data thus suggests that these SNPs do not affect breast cancer risk in the tested population. In addition, rs199981120, rs185641358, and rs113054794 could not be found in this population, suggesting that these SNPs do not occur in Caucasian Australians.

The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts

Heparan sulfate proteoglycans cooperate with basic fibroblast growth factor (bFGF/FGF2) signaling to control osteoblast growth and differentiation, as well as metabolic functions of osteoblasts. FGF2 signaling modulates the expression and activity of Runt-related transcription factor 2 (Runx2/Cbfa1), a key regulator of osteoblast proliferation and maturation. Here, we have characterized novel Runx2 target genes in osteoprogenitors under conditions that promote growth arrest while not yet permitting sustained phenotypic maturation. Runx2 enhances expression of genes related to proteoglycan-mediated signaling, including FGF receptors (e.g., FGFR2 and FGFR3) and proteoglycans (e.g., syndecans [Sdc1, Sdc2, Sdc3], glypicans [Gpc1], versican [Vcan]). Runx2 increases expression of the glycosyltransferase Exostosin-1 (Ext1) and heparanase, as well as alters the relative expression of N-linked sulfotransferases (Ndst1 = Ndst2 > Ndst3) and enzymes mediating O-linked sulfation of heparan sulfate (Hs2st > Hs6st) or chondroitin sulfate (Cs4st > Cs6st). Runx2 cooperates with FGF2 to induce expression of Sdc4 and the sulfatase Galns, but Runx2 and FGF2 suppress Gpc6, thus suggesting intricate Runx2 and FGF2 dependent changes in proteoglycan utilization. One functional consequence of Runx2 mediated modulations in proteoglycan-related gene expression is a change in the responsiveness of bone markers to FGF2 stimulation. Runx2 and FGF2 synergistically enhance osteopontin expression (>100 fold), while FGF2 blocks Runx2 induction of alkaline phosphatase. Our data suggest that Runx2 and the FGF/proteoglycan axis may form an extracellular matrix (ECM)-related regulatory feed-back loop that controls osteoblast proliferation and execution of the osteogenic program.

Tandem B1 SINE retro-elements may provide a basis for natural antisense transcription in the Magi1 locus of the mouse (Mus musculus)

Transposable elements, which are DNA sequences that can move between different sites in genomes, comprise approximately 40% of the genome of mammals and are emerging as important contributors to biological diversity. Here we report a transcription unit lying within intron 1 of the murine Magi1 (membrane associated guanylate kinase inverted 1) gene that codes for a cell-cell junction scaffolding protein. The transcription unit, termed Magi1OS (Magi1 Opposite Strand), originates from a region with tandem B1 short interspersed nuclear elements (SINEs) and is an antisense gene to Magi1. Mag1OS transcription initiates in a proximal B1 element that shows only 4% divergence from the consensus sequence, indicating that it has been recently inserted into the mouse genome and could be replication competent. Moreover, a chimaeric transcript may result from intra-chromosomal interaction and trans-splicing of the Magi1 antisense transcript (Magi1OS) and Ghrl, which codes for the multifunctional peptide hormone ghrelin. These two genes are 20 megabases apart on chromosome 6 and are transcribed in opposite directions. We propose that the Magi1OS locus may serve as a useful model system to study exaptation and retrotransposition of B1 SINEs, as well as to examine the mechanisms of intra-chromosomal trans-splicing.

Quantitative genetic parameters for body traits at different ages in a cultured stock of giant freshwater prawn (Macrobrachium rosenbergii) selected for fast growth

The aim of the current study was to estimate heritabilities and correlations for body traits at different ages (Weeks 10 and 18 after stocking) in a giant freshwater prawn (Macrobrachium rosenbergii) population selected for fast growth rate in Vietnam. The dataset consisted of 4650 body records (2432 and 2218 records collected at Weeks 10 and 18, respectively) in the full pedigree comprising a total of 18 387 records. Variance and covariance components were estimated using restricted maximum likelihood fitting a multi-trait animal model. Estimates of heritability for body traits (bodyweight, body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width) were moderate and ranged from 0.06 to 0.11 and from 0.11 to 0.22 at Weeks 10 and 18, respectively. Body-trait heritabilities estimated at Week 10 were not significantly lower than at Week 18. Genetic correlations between body traits within age and genetic correlations for body traits between ages were generally high. Our results suggested that selection for high growth rate in GFP can be undertaken successfully before full market size has been reached.

Hybrid genetic algorithm for elimination of severe stress concentration in railhead ends

This paper presents a computational method for eliminating severe stress concentration at the unsupported railhead ends in rail joints through innovative shape optimization of the contact zone, which is complex due to near field nonlinear contact. With a view to minimizing the computational efforts, hybrid genetic algorithm method coupled with parametric finite element has been developed and compared with the traditional genetic algorithm (GA). The shape of railhead top surface where the wheel contacts nonlinearly was optimized using the hybridized GA method. Comparative study of the optimal result and the search efficiency between the traditional and hybrid GA methods has shown that the hybridized GA provides the optimal shape in fewer computational cycles without losing accuracy. The method will be beneficial to solving complex engineering problems involving contact nonlinearity.

A new grouping genetic algorithm for the MapReduce placement problem in cloud computing

MapReduce is a computation model for processing large data sets in parallel on large clusters of machines, in a reliable, fault-tolerant manner. A MapReduce computation is broken down into a number of map tasks and reduce tasks, which are performed by so called mappers and reducers, respectively. The placement of the mappers and reducers on the machines directly affects the performance and cost of the MapReduce computation. From the computational point of view, the mappers/reducers placement problem is a generation of the classical bin packing problem, which is NPcomplete. Thus, in this paper we propose a new grouping genetic algorithm for the mappers/reducers placement problem in cloud computing. Compared with the original one, our grouping genetic algorithm uses an innovative coding scheme and also eliminates the inversion operator which is an essential operator in the original grouping genetic algorithm. The new grouping genetic algorithm is evaluated by experiments and the experimental results show that it is much more efficient than four popular algorithms for the problem, including the original grouping genetic algorithm.

Composite SaaS scaling in cloud computing using a hybrid genetic algorithm

A Software-as-a-Service or SaaS can be delivered in a composite form, consisting of a set of application and data components that work together to deliver higher-level functional software. Components in a composite SaaS may need to be scaled – replicated or deleted, to accommodate the user’s load. It may not be necessary to replicate all components of the SaaS, as some components can be shared by other instances. On the other hand, when the load is low, some of the instances may need to be deleted to avoid resource underutilisation. Thus, it is important to determine which components are to be scaled such that the performance of the SaaS is still maintained. Extensive research on the SaaS resource management in Cloud has not yet addressed the challenges of scaling process for composite SaaS. Therefore, a hybrid genetic algorithm is proposed in which it utilises the problem’s knowledge and explores the best combination of scaling plan for the components. Experimental results demonstrate that the proposed algorithm outperforms existing heuristic-based solutions.

Progress in epithelial-mesenchymal transition research

The field of research of epithelial-mesenchymal transitions, EMT, and its reverse, mesenchymal-epithelial transitions, MET, has expanded very rapidly indeed from its beginnings, heralded by Professor Betty Hay in the 1970s and 1980s. This expansion has involved the realisation that the EMT was not just an interesting phenomenon of early developmental morphogenetic cell behaviour, but bore remarkable resemblance to clinically crucial pathological events in cancer invasion. Not surprisingly, this discipline soon became numerically dominant in the EMT publication field. Simultaneously, the EMT concept has been extended to normal physiological wound healing. Exploration revealed that these resemblances were more than skin deep: the same sets of growth factors, receptors, transcription factors, epigenetic marks and signalling pathways turned up repeatedly in EMTs and METs in a variety of contexts, both pathological and normal. This molecular genetic research in turn uncovered similarities of the EMT signature to that of fibrosis, a set of diseases which is of enormous clinical importance, rivalling that of cancer. Most recently, and more surprisingly, the EMT signature has shown considerable similarity to that found in stem cell and cancer stem cell biology.

Transcriptional regulation of flavonoid biosynthesis in nectarine (Prunus persica) by a set of R2R3 MYB transcription factors

Background Flavonoids such as anthocyanins, flavonols and proanthocyanidins, play a central role in fruit colour, flavour and health attributes. In peach and nectarine (Prunus persica) these compounds vary during fruit growth and ripening. Flavonoids are produced by a well studied pathway which is transcriptionally regulated by members of the MYB and bHLH transcription factor families. We have isolated nectarine flavonoid regulating genes and examined their expression patterns, which suggests a critical role in the regulation of flavonoid biosynthesis. Results In nectarine, expression of the genes encoding enzymes of the flavonoid pathway correlated with the concentration of proanthocyanidins, which strongly increases at mid-development. In contrast, the only gene which showed a similar pattern to anthocyanin concentration was UDP-glucose-flavonoid-3-O-glucosyltransferase (UFGT), which was high at the beginning and end of fruit growth, remaining low during the other developmental stages. Expression of flavonol synthase (FLS1) correlated with flavonol levels, both temporally and in a tissue specific manner. The pattern of UFGT gene expression may be explained by the involvement of different transcription factors, which up-regulate flavonoid biosynthesis (MYB10, MYB123, and bHLH3), or repress (MYB111 and MYB16) the transcription of the biosynthetic genes. The expression of a potential proanthocyanidin-regulating transcription factor, MYBPA1, corresponded with proanthocyanidin levels. Functional assays of these transcription factors were used to test the specificity for flavonoid regulation. Conclusions MYB10 positively regulates the promoters of UFGT and dihydroflavonol 4-reductase (DFR) but not leucoanthocyanidin reductase (LAR). In contrast, MYBPA1 trans-activates the promoters of DFR and LAR, but not UFGT. This suggests exclusive roles of anthocyanin regulation by MYB10 and proanthocyanidin regulation by MYBPA1. Further, these transcription factors appeared to be responsive to both developmental and environmental stimuli.

Analysis of genetically modified red-fleshed apples reveals effects on growth and consumer attributes

Consumers of whole foods, such as fruits, demand consistent high quality and seek varieties with enhanced health properties, convenience or novel taste. We have raised the polyphenolic content of apple by genetic engineering of the anthocyanin pathway using the apple transcription factor MYB10. These apples have very high concentrations of foliar, flower and fruit anthocyanins, especially in the fruit peel. Independent lines were examined for impacts on tree growth, photosynthesis and fruit characteristics. Fruit were analysed for changes in metabolite and transcript levels. Fruit were also used in taste trials to study the consumer perception of such a novel apple. No negative taste attributes were associated with the elevated anthocyanins. Modification with this one gene provides near isogenic material and allows us to examine the effects on an established cultivar, with a view to enhancing consumer appeal independently of other fruit qualities. © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

An ancient duplication of apple MYB transcription factors is responsible for novel red fruit-flesh phenotyp

Anthocyanin accumulation is coordinated in plants by a number of conserved transcription factors. In apple (Malus × domestica), an R2R3 MYB transcription factor has been shown to control fruit flesh and foliage anthocyanin pigmentation (MYB10) and fruit skin color (MYB1). However, the pattern of expression and allelic variation at these loci does not explain all anthocyanin-related apple phenotypes. One such example is an open-pollinated seedling of cv Sangrado that has green foliage and develops red flesh in the fruit cortex late in maturity. We used methods that combine plant breeding, molecular biology, and genomics to identify duplicated MYB transcription factors that could control this phenotype. We then demonstrated that the red-flesh cortex phenotype is associated with enhanced expression of MYB110a, a paralog of MYB10. Functional characterization of MYB110a showed that it was able to up-regulate anthocyanin biosynthesis in tobacco (Nicotiana tabacum). The chromosomal location of MYB110a is consistent with a whole-genome duplication event that occurred during the evolution of apple within the Maloideae family. Both MYB10 and MYB110a have conserved function in some cultivars, but they differ in their expression pattern and response to fruit maturity.

Genetic technologies and the regulation of reproductive decision-making in Australia

This article provides a critical analysis of the current Australian regulatory landscape at the interface between genetics and reproductive decision- making. The authors argue that a comparative analysis with other countries and international law and a contextual examination of the way law regulates concepts such as disease and health, abnormality and normality is necessary before we can develop appropriate policy and legislative responses in this area. Specific genetic testing technologies are considered including prenatal genetic testing, preimplantation genetic diagnosis and inheritable genetic modification. An increasing number of members of the Australian community are using genetic testing technologies when they decide to have a baby. The authors argue that as concepts of disease and health vary among members of the community and the potential to test for traits other than illness increases, a new tension arises between an ethic of individual choice and a role for government in regulating reproductive decision-making.