12 fingers or one, it’s how you play? Genetic discrimination in the Australian workforce

For quite some time, debate has raged about what the human race can and should do with its knowledge of genetics. We are now nearly 60 years removed from the work of Watson and Crick who determined the structure of deoxyribonucleic acid (DNA), yet our opinions as how best to employ scientific knowledge of the human genome, remain as diverse and polarised as ever. Human judgment is often shaped and coloured by popular media and culture, so it should come as no surprise that box office movies such as Gattaca (1997) continue to play a role in informing public opinion on genetics. In order to perform well at the box office, movies such as Gattaca take great liberty in sensationalising (and even distorting) the implications that may result from genetic screening and testing. If the public’s opinion on human genetics is strongly derived from the box office and popular media, then it is no wonder that the discourse on human genetics is couched in the polar parlances of future utopias or future dystopias. When legislating in an area like genetic discrimination in the workforce, we must be mindful of not overplaying the causal link between genetic predisposition towards a disability and an employee’s ability to perform the inherent requirements of their job. Genetic information is ultimately about people, it is not about genes. Genetic discrimination is ultimately about actions, it is not about the intrinsic value of genetic information.

Blast atlas: a virtual observatory for genomes

Following the completion of the draft Human Genome in 2001, genomic sequence data is becoming available at an accelerating rate, fueled by advances in sequencing and computational technology. Meanwhile, large collections of astronomical and geospatial data have allowed the creation of virtual observatories, accessible throughout the world and requiring only commodity hardware. Through a combination of advances in data management, data mining and visualization, this infrastructure enables the development of new scientific and educational applications as diverse as galaxy classification and real-time tracking of earthquakes and volcanic plumes. In the present paper, we describe steps taken along a similar path towards a virtual observatory for genomes – an immersive three-dimensional visual navigation and query system for comparative genomic data.

Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

The genetics of cutaneous melanoma

Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.

Challenges to environmental toxicology and epidemiology : where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today’s settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene–environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

Review : alternative splicing (AS) of genes as an approach for generating protein complexity

Prior to the completion of the human genome project, the human genome was thought to have a greater number of genes as it seemed structurally and functionally more complex than other simpler organisms. This along with the belief of “one gene, one protein”, were demonstrated to be incorrect. The inequality in the ratio of gene to protein formation gave rise to the theory of alternative splicing (AS). AS is a mechanism by which one gene gives rise to multiple protein products. Numerous databases and online bioinformatic tools are available for the detection and analysis of AS. Bioinformatics provides an important approach to study mRNA and protein diversity by various tools such as expressed sequence tag (EST) sequences obtained from completely processed mRNA. Microarrays and deep sequencing approaches also aid in the detection of splicing events. Initially it was postulated that AS occurred only in about 5%; of all genes but was later found to be more abundant. Using bioinformatic approaches, the level of AS in human genes was found to be fairly high with 35-59%; of genes having at least one AS form. Our ability to determine and predict AS is important as disorders in splicing patterns may lead to abnormal splice variants resulting in genetic diseases. In addition, the diversity of proteins produced by AS poses a challenge for successful drug discovery and therefore a greater understanding of AS would be beneficial.

Library Research Support in developing, testing and promoting an open cyberinfrastructure

QUT Library continues to rethink research support with eResearch as a primary driver. The support to the development of the Lens, an open global cyberinfrastructure, has been especially important in the light of technology transfer promotion, and partly in the response to researchers’ needs in following the innovation landscapes not only within the scientific but also patent literature. The Lens http://www.lens.org/lens/ project makes innovation more efficient, fair, transparent and inclusive. It is a joint effort between Cambia http://www.cambia.org.au and Queensland University of Technology (QUT). The Lens serves more than 84 million patent documents in the world as open, annotatable digital public goods that are integrated with scholarly and technical literature along with regulatory and business data. Users can link from search results to visualization and document clusters; from a patent document description to its full-text; from there, if applicable, the sequence data can also be found. Figure 1 shows a BLAST Alignment (DNA) using the Lens. A unique feature of the Lens is the ability to embed search and BLAST results into blogs and websites, and provide real-time updates to them. PatSeq Explorer http://www.lens.org/lens/bio/patseqexplorer allows users to navigate patent sequences that map onto the human genome and in the future, many other genomes. PatSeq Explorer offers three level views for the sequence information and links each group of sequences at the chromosomal level to their corresponding patent documents in the Lens. By integrating sequence and patent search and document clustering capabilities, users can now understand the big and small details on the true extent and scope of genetic sequence patents. QUT Library supported Cambia in developing, testing and promoting the Lens. This poster demonstrates QUT Library’s provision of best practice and holistic research support to a research group and how QUT Librarians have acquired new capabilities to meet the needs of the researchers beyond traditional research support practices.

Women's health in the global village

As we stand at the beginning of the 21st century and behold the world before us, it seems that we are living in a time of profound change. Everywhere we look change seems afoot, demolishing our traditional securities and hastily building new ones in their place. Modern medical science has been an integral part of this change. It is not possible to ignore the advances of modern medicine nor the realities of scientific uncertainties for they are part of the shared context of our lives today. I In the past 50 years we have witnessed the discovery of DNA and more recently the mapping of the human genome, the birth of the world's first in-vitro fertilisation baby, followed by thousands worldwide in the period since, the discovery of human stem cells and the birth of Dolly the cloned sheep in Scotland. Furthermore, the processes of globalisation have ensured that an event that occurs on one side of the globe becomes an item on the evening news on the other side, creating the impression that all change takes place on our doorstep. Some of these events have provoked deep angst in the community, sparking public debate over the ethics of science and the boundaries to be imposed by law. All of these developments have changed the realm of the possible. While these advances in medical science spark debate in the developed countries, in less developed countries high rates of infectious diseases and infant and maternal mortality and the challenges of access to adequate food and clean water are priorities, highlighting international differences in health care. This article explores these differences through an analysis of globalisation and reproduction. It seeks to analyse both the meaning of globalisation and the impact of globalising trends on health laws and policies as regulators of women's health within the global village.

Exploring the scope of gene patents through new levels of transparency

As the global intellectual property (IP) system grows and now impacts virtually all citizens, it is crucial that the means to understand these rights and their teachings, as well as their implications and scope become global public goods. To do so requires not only that the primary data is available freely and openly in a standardized and re-useable form, but that tools to visualize, analyse and model that data are similarly open and free public goods, adaptable to diverse needs and uses; this we call ‘transparency’.

Computational micromodel for epigenetic mechanisms

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach.

The future for genetic studies in reproduction

Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies(GWAS) have revolutionized gene discovery forcommontraits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases.GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.

After the gold rush: Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. ’For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: ’There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as ’novelty', ’inventive step', and ’utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the ’Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

Japonica rice: Intellectual property, scientific publishing and data-sharing

This article examines a series of controversies within the life sciences over data sharing. Part 1 focuses upon the agricultural biotechnology firm Syngenta publishing data on the rice genome in the journal Science, and considers proposals to reform scientific publishing and funding to encourage data sharing. Part 2 examines the relationship between intellectual property rights and scientific publishing, in particular copyright protection of databases, and evaluates the declaration of the Human Genome Organisation that genomic databases should be global public goods. Part 3 looks at varying opinions on the information function of patent law, and then considers the proposals of Patrinos and Drell to provide incentives for private corporations to release data into the public domain.

The genographic project: Traditional knowledge and population genetics

This article considers the debate over patent law, informed consent, and benefit-sharing in the context of biomedical research in respect of Indigenous communities. In particular, it focuses upon three key controversies over large-scale biology projects, involving Indigenous populations. These case studies are representative of the tensions between research organisations, Indigenous communities, and funding agencies. Section two considers the aims and origins of the Human Genome Diversity Project, and criticisms levelled against the venture by Indigenous peak bodies and anti-biotechnology groups, such as the Rural Advancement Foundation International. It examines the ways in which the United Nations Educational, Scientific, and Cultural Organization (UNESCO) grappled with questions of patent law, informed consent, and benefit sharing in relation to population genetics. Section three focuses upon the ongoing litigation in Tilousi v. Arizona State University, and the Havasupai Tribe v. Arizona State University. In this matter, the Havasupai tribe from the Grand Canyon in the United States brought legal action against the Arizona State University and its researchers for using genetic data for unauthorised purposes - namely, genetic research into schizophrenia, migration, and inbreeding. The litigation raises questions about informed consent, negligence, and larger matters of human rights. Section four explores the legal and ethical issues raised by the Genographic Project. It considers the aims and objectives of the venture, and the criticisms levelled against it by Indigenous communities, and anti-biotechnology groups. It examines the response of the United Nations Permanent Forum on Indigenous Issues to the Genographic Project. It charts the debate over the protection of traditional knowledge in various international fora. The conclusion recommends a number of measures to better regulate large-scale biology projects involving the participation of Indigenous communities.

Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. 'For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: 'There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as 'novelty', 'inventive step', and 'utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the 'Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.