This timely work brings together a group of the nation's leading experts in genetics, medicine, history of science, health, law, philosophy of science, and medical ethics to assess the current state of modern human genetics, and to begin to chart the legal and ethical guidelines needed to prevent the misuse of human genetics from leading to the abuse of human beings. The six sections of the book, read together, map the social policy con tours of modern human genetics. The first (...) part describes the science of the Human Genome Project. The second addresses specific social policy implications, including the relevance of recombinant DNA history, the eugenics legacy, military applications, and issues of race and class in the context of genetic discrimination. Broader philosophical issues, including reductionism and determinism, the concept of disease, and using germline gene therapy to "improve" human beings are discussed in the third part. (shrink)

Neuroethics to date has tended to focus on social and ethical implications of developments in brain science, especially in functional neuroimaging. Within clinical neuroethics, the emphasis has been on ethical issues in clinical neuroscience practice, including informed consent to neuroimaging; the development of ethical research protocols for functional magnetic resonance imaging especially, and especially in children; and the ethical clinical management of incidental findings. Within normative neuroethics, we have witnessed the more philosophical and/or social scientific study of the meanings of (...) developments in neuroscience, including concerns about the impact of neuroimaging on privacy, freedom of thought, moral culpability, and sense of self. In this piece, I argue for an expansion of neuroethical attention to the interface of neuroscience and psychiatry, where brain science meets the clinical sciences of the mind. My particular focus is the development of psychiatric classification systems. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only (...) sharpened the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity (...) with rice of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

“What is a gene?” is an important philosophical question that has been asked over and over. This paper approaches this question by understanding it as the individuation problem of genes, because it implies the problem of identifying genes and identifying a gene presupposes individuating the gene. I argue that there are at least two levels of the individuation of genes. The transgenic technique can individuate “a gene” as an individual while the technique of gene (...) class='Hi'>mapping in classical genetics can only individuate “a gene” as a type or a kind. The two levels of individuation involve different techniques, different objects that are individuated, and different references of the term “gene”. Based on the two levels of individuation, I discuss important philosophical implications including the relationship between individuality and individuation and that between individuals and kinds in experimental contexts. I also suggest a new gene conception, calling it “the transgenic conception of the gene.”. (shrink)

This paper describes one complete and one ongoing empirical study in which philosophical analyses of the concept of the gene were operationalized and tested against questionnaire data obtained from working biologists to determine whether and when biologists conceive genes in the ways suggested. These studies throw light on how different gene concepts contribute to biological research. Their aim is not to arrive at one or more correct 'definitions' of the gene, but rather to map out the variation (...) in the gene concept and to explore its causes and its effects. (shrink)

The properties of DNA -- DNA as universal property -- DNA as intellectual property -- DNA as national property -- DNA as personal property -- DNA as academic property -- DNA as taxable propety.

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 10.3 (2000) 265-281 [Access article in PDF] Scope Note 39 Genes, Patents, and Bioethics-Will History Repeat Itself? Susan Cartier Poland Gene patenting--the very notion sounds absurd! How can anyone claim to have invented the genes with which one is born? To make matters worse, genetic makeup precedes birth, meaning the existence of the invention predates the existence of the inventor. So, do we (...) really own our genes, or do they belong to our parents, or our governments, or a Supreme Being? Ownership is only one bioethical issue involved in gene patenting. But before looking at the issues, some essential and basic terms must be understood, namely genes and patents. Genes In his book On the Origin of Species, published in 1859, the biologist Charles Darwin proposed a theory called "natural selection," whereby living things changed over time or evolved through generations due to competition and variation. By experimenting with the garden pea in the 1860s, Gregor Mendel, a monk and accomplished horticulturalist, provided the mechanism of inheritance supporting the natural selection theory of his contemporary Darwin. That mechanism is the gene, or, as Mendel described it, a discrete "factor." The gene has also been defined as "the fundamental unit of heredity" (United States 1987, p. 157). Each individual has two copies of a gene, one from each parent, but that individual passes down to offspring only one of the two copies. Because of Mendel, the gene has become a scientific concept and the basis of a new scientific field: genetics.David C. Page (2000) of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology explained today's terms for genetics structures using an analogy taken from the home. In his view, the cell is a kitchen, the genome is a shelf in the kitchen, the chromosome is a cookbook on the shelf, the gene is a recipe in the cookbook, and a base-pair (either adenine with thymine or guanine with cytosine) is a single letter in the recipe. A protein, the [End Page 265] working molecule blueprinted by a gene, is a dish ready to eat, and an ingredient in the dish is an amino acid, which is a building block of the protein as specified by a string of base-pairs.Colin Tudge (1993), a British science journalist, would disagree with Page's description of the gene as a recipe. A recipe is like a blueprint: both are directions that precede the work. But a gene is not passive according to Tudge; it actively administers the cell's work, and it also responds to cellular events (Aldridge 1996).The current focus of scientific research and funding is on the gene and the completion of the sequencing of all the genes that comprise the human genome, portrayed in the press as a race between the U.S. government's Human Genome Project and the private corporation Celera Genomics. The real action, however, is at the protein level. The gene only holds the information to produce a protein; it is the three-dimensional shaped protein that does the work. In order to produce energy, eliminate waste, and perform other functions specific to a cell or tissue, proteins must bind, thus creating "biological pathways." Proteins bind (or not) and detach as a function of their shapes, which are determined by their precise chemical composition as spelled out in their genetic code. IBM will spend the next five years making one computer, Blue Gene, that will then take an entire year to come up with the chemical map for only one protein (Gillis 2000). It is estimated that there are about 40,000 proteins in the human body.Despite these overwhelming numbers, modern biology has been able to achieve significant results within the Human Genome Project's 15-year time frame, from 1990 to 2005. The genetic map was completed in 1993; the physical map was completed in 1995; and the genetic sequence is expected to be completed in 2002, with 97 to 99 percent completed as of 26 June 2000. This... (shrink)

Arabidopsis thaliana (Thale cress, Arabidopsis) is an ideal model organism for the molecular genetic analysis of many plant processes. The availability of a complete physical map would greatly facilitate the gene cloning steps in these studies. The small genome size of Arabidopsis makes the construction of such a map a feasible goal. One of the approaches to construct an overlapping library of the Arabidopsis genome takes advantage of the many mapped markers and the availability of Arabidopsis yeast artificial chromosome (...) (YAC) libraries. Mapped molecular markers are used to identify corresponding YAC clones and thereby place them on the genetic map. Subsequently, these YAC clones provide the framework for directed walking experiments aimed at closing the gaps between the YAC contigs. Adopting this strategy, YAC clones comprising about 10% of the genome have been assigned to the top halves of Arabidopsis chromosomes 4 and 5. Extensive walking experiments in a 10 cM interval of chromosome 4 have resulted in two contiguous regions in the megabase size range. (shrink)

For at least a century it has been known that multiple factors play a role in the development of complex traits, and yet the notion that there are genes “for” such traits, which traces back to Mendel, is still widespread. In this paper, we illustrate how the Mendelian model has tacitly encouraged the idea that we can explain complexity by reducing it to enumerable genes. By this approach many genes associated with simple as well as complex traits have been identified. (...) But the genetic architecture of biological traits, or how they are made, remains largely unknown. In essence, this reflects the tension between reductionism as the current “modus operandi” of science, and the emerging knowledge of the nature of complex traits. Recent interest in systems biology as a unifying approach indicates a reawakened acceptance of the complexity of complex traits, though the temptation is to replace “gene for” thinking by comparably reductionistic “network for” concepts. Both approaches implicitly mix concepts of variants and invariants in genetics. Even the basic question is unclear: what does one need to know to “understand” the genetic basis of complex traits? New operational ideas about how to deal with biological complexity are needed. (shrink)

It is somewhat ironic that animals that are the prime choice for detailed genetic analysis, such as the fruit fly and the nematode, have thus far been largely refractory to reverse genetic analysis. Their detailed genetic map, and small genome size have made them subjects of ambitious genome analysis projects, but there is still no strategy to introduce desired changes into their genomes by homologous recombination. Some alternative approaches have recently become available; this review describes possibilities and unsolved problems for (...) reverse genetics in the nematode Caenorhabditis elegans. The transposon Tc1 could prove to be very useful for the isolation of knock out mutants, and possibly also for introduction of more subtle alterations. (shrink)

Wheat is an allopolyploid containing three distinct but genetically related (homoeologous) genomes, A, B and D. Because of polyploid inheritance and large genome size (16×1012 bp), the wheat genome is thought to be intractable to map‐based cloning of agronomic and other genes of interest. We propose a targeted geneti mapping strategy that combines linkage and physical mapping and may facilitate map‐based cloning. High‐density linkage maps are either generated in wheat or in diploid Triticum tauschii, the donor of the (...) D genome to wheat. Molecular marker‐based chromosome maps are constructed, using an array of deletion lines in wheat. The conventional genetic linkage maps are aligned with chromosome maps to construct cytogenetic ladder maps (CLMs). The CLMs allow region‐specific mapping and convert genetic distances into physical distances. The information from CLMs suggests that many genes in wheat are present in clusters that are highly recombiogenic, small, and may be amenable to cloning by chromosome walking. Therefore, the effective genome size of wheat is relatively small in comparison to the whole genome. The utility of using the smaller genome of rice for mapping and homologous gene cloning is discussed. (shrink)

A total of 944 expressed sequence tags generated 2212 EST loci mapped to homoeologous group 1 chromosomes in hexaploid wheat. EST deletion maps and the consensus map of group 1 chromosomes were constructed to show EST distribution. EST loci were unevenly distributed among chromosomes 1A, 1B, and ID with 660, 826, and 726, respectively. The number of EST loci was greater on the long arms than on the short arms for all three chromosomes. The distribution of ESTs along chromosome arms (...) was nonrandom with EST clusters occurring in the distal regions of short arms and middle regions of long arms. Duplications of group 1 ESTs in other homoeologous groups occurred at a rate of 35.5%. Seventy-five percent of wheat chromosome 1 ESTs had significant matches with rice sequences, where large regions of conservation occurred between wheat consensus chromosome 1 and rice chromosome 5 and between the proximal portion of the long arm of wheat consensus chromosome 1 and rice chromosome 10. Only 9.5% of group 1 ESTs showed significant matches to Arabidopsis genome sequences. The results presented are useful for gene mapping and evolutionary and comparative genomics of grasses. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

My aim in this paper is to quickly sketch a teleological approach to the problem of isolating the impact of genes on phenotypic characters. I begin by arguing that it is a mistake to think that there will be only one analysis of genetic input suitable for all theoretical interests. My principle focus is Richard Dawkins' argument for genic selectionism. I argue that a teleological analysis of genetic input is what Dawkins requires to establish the right kind of mapping (...) of gene onto phenotype. This comes at a certain cost, however. Accepting the analysis will threaten Dawkins' claims about the teleogogical priority of gene over phenotype. (shrink)

The revolutionary potential of the CRISPR-Cas9 gene editing technique has created a resurgence in enthusiasm and concern in genetic research perhaps not seen since the mapping of the human genome at the turn of the century. Some such concerns and anxieties revolve around crossing lines between somatic and germline interventions as well as treatment and enhancement applications. Underpinning these concerns, there are familiar concepts of safety, unintended consequences and damage to genetic identity and the creation of designer children (...) through pursuing human enhancement and eugenics. In the policy realm, these morally laden distinctions and anxieties are emerging as the basis for making important and applied measures to respond to the fast-evolving scientific developments. This paper argues that the dominant normative framing for such responses is insufficient for this task. This paper illustrates this insufficiency as arising from a continued reliance on misleading genetic essentialist assumptions that generate groundless speculation and over-reactionary normative responses. This phenomenon is explicit with regard to prospective human genetic enhancements. While many normative theorists and state-of-the-art reports continue to gesture toward the influence of environmental and social influences on a person and their traits and capacities, this recognition does not extend to the substance of the arguments themselves which tend to revert to the debunked genetic determinist framework. Given the above, this paper argues that there is a pressing need for a more central role for sociological input into particular aspects of this “enhancement myth” in order to give added weight, detail and substance to these environmental influences and influence from social structures. (shrink)

On June 26, 2000, President Clinton, together with Francis Collins and Craig Venter, solemnly announced, from the East Room of the White House, that the grand effort to sequence the human genome, the Human Genome Project (HGP), was rapidly nearing its completion. Symbolism abounded. The event was framed as a crucial marker in the history of both humanity and knowledge by explicitly connecting the completion of the HGP with a number of already acknowledged and established scientific highlights. Tensions abounded as (...) well, however, notably between competing metaphors. In the course of the HGP, metaphors had become crucially important in framing and conveying what the HGP was really about. They had proved themselves to be of key importance when it came to defining and explaining the project’s significance for both science and society. Powerful images and metaphors had been deployed in order to secure unprecedented amounts of funding, on the one hand by comparing the HGP to other big technoscientific projects such as space travel, high energy physics, the atomic bomb and a territorial mapping exercise, and on the other hand through the suggestion that, once we have our “blueprint”, “code of codes”, “parts list”, etc. available, cancer genes will no longer have a place to hide. This article sets out to analyze this clash of metaphors, firmly embedded within the HGP but culminating at the press conference, arguing that the June 2000 event is even reminiscent of a somewhat similar event, depicted by a famous altarpiece, ‘The adoration of the Lamb’, on display in Ghent Cathedral and finished more than five centuries before. (shrink)

The author explores the ethics of decision-making and confidentiality in donor insemination through the narrative of her experience having two children with a sperm donor who was later discovered to carry a gene for a serious heart disease, hypertrophic cardiomyopathy. Contrasting individualist and communitarian ethical models, she questions understandings of confidentiality that hamper the construction of a medical family tree, especially when prognosis and treatment depend on the larger familial profile of the disease. She also emphasises that for the (...) patient family the discovery of biological family through the lens of transmitted illness leads to a shift in family identity that goes beyond the purely medical. (shrink)

Following the Second Summit on Human Gene Editing in Hong Kong in 2018, where the birth of two girls with germline genome editing was revealed, the need for a responsible pathway to the clinical application of human germline genome editing has been repeatedly emphasised. This paper aims to contribute to the ongoing discussion on research ethics issues in germline genome editing by exploring key issues related to the initial applications of CRISPR in reproductive medicine. Following an overview of the (...) current discussion on bringing germline genome editing into clinical practice, we outline the specific challenges associated with such interventions and the features that distinguish them from conventional clinical testing of new medical treatments. We then review proposed ethical requirements for initial heritable genome editing, such as the absence of reasonable alternatives, the existence of sufficient and reliable preclinical data, appropriate informed consent, requirements related to safety, and long-term follow-up. (shrink)

Understanding the clinical significance of variants associated with hereditary cancer risk requires access to a pooled data resource or network of resources—a “cancer gene variant commons”—incorporating representative, well-characterized genetic data, metadata, and, for some purposes, pathways to case-level data. Several initiatives have invested significant resources into collecting and sharing cancer gene variant data, but further progress hinges on identifying and addressing unresolved policy issues. This commentary provides insights from a modified policy Delphi process involving experts from a range (...) of stakeholder groups involved in the data-sharing ecosystem. In particular, we describe policy issues and options generated by Delphi participants in five domains critical to the development of an effective cancer gene variant commons: incentives, financial sustainability, privacy and security, equity, and data quality. Our intention is to stimulate wider discussion and lay a foundation for further work evaluating policy options more in-depth and mapping them to those who have the power to bring about change. Addressing issues in these five domains will contribute to a cancer gene variant commons that supports better care for at-risk and affected patients, empowers patient communities, and advances research on hereditary cancers. (shrink)

ESTs or ‘expressed sequence tags’ are DNA sequences read from both ends of expressed gene fragments. The Merck‐WashU EST Project and several other public EST projects are being performed to rapidly discover the complement of human genes, and make them easily accessible. These ESTs are widely used to discover novel members of gene families, to map genes to chromosomes as ‘sequence‐tagged sites’ (STSs), and to identify mutations leading to heritable diseases. Informatic strategies for querying the EST databases are (...) discussed, as well as the strengths and weaknesses of the EST data. There is a compelling need to build on the informatic synthesis of human gene data, and to devise facile methods for determining gene functions. (shrink)

The Affymetrix GeneChip is a popular microarray platform for genome‐wide expression profiling and has been widely used in functional genomics especially in the classification of cancers. Due to the updating of genome data, much of the genome information with which the chips were designed is out‐of‐date and it has been reported that many of the genes/transcripts on the chips differ from their original definition when mapping the probes to the new genome information. Dai et al. have reported that the (...) updated definition can cause as much as 30–50% discrepancy in the genes selected as differentially expressed on a heart tissue expression profiling dataset. Understanding the nature of this difference is therefore very important for the utilization of the data. In this work, with a large cancer dataset as an example, we compared two major definitions and investigated their effects on classification, clustering, discovery of differentially expressed genes and gene‐set‐based analysis. Results show that the two definitions agree well on clustering and classification results but genes and gene sets discovered as differentially expressed or enriched can be very different. Discoveries based on the Affymetrix definition can cover most of those based on the new definition, but tend to have more false positives. BioEssays 28: 739–746, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This paper explores the historical and social context of population genetic research conducted in India by focusing on a study by Reich et al which aimed to reconstruct Indian population history. The paper addresses two themes. First, it considers the agendas and modes of thinking about Indian populations and the caste system on which this study appears to be based. Second, it reflects on the medical implications of this study as they were presented in Reich et al's findings. I suggest (...) that while genetic mapping of Indian populations appears to have inherited many of the problems characteristic of population genetic research conducted in the USA and globally, the specificity of this research in India involves a peculiar interplay of the postcolonial pursuit of genomic sovereignty, desire by the Indian state to become a player in the global realm of biotechnology, and age-old discourses naturalising caste and regional differences. My argument is that, although the study has offered conceptual space for a wide range of interpretations, it has a strong potential not just for naturalising caste and regional differences in India, but also for pathologising them without necessarily bringing tangible healthcare benefits in the foreseeable future. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated (...) loci in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

After ten years of debate Directive 98/44/EG on the legal protection of biotechnological inventions was adopted in 1998. This directive takes decisions on some controversial bioethical and legal issues and offers the European biotech industries more space to develop their inventions, but leaves a number of philosophical and moral issues unresolved. This paper distinguishes between different layers in the debate and maps its modes of argumentation. Major philosophical, ethical and conceptual issues are located. It is argued that further analysis of (...) these issues can help resolve further ethical and legal difficulties as regards patenting of human DNA. As the allegedly special status of genetic material remains unclear, the status of (human) DNA and its relation to the human body and personal identity should be further explored. (shrink)

Mechanisms involved in the regulation of development and its genetic control are receiving ever‐increasing attention in studies of mammalian developmental genetics. The potential success of such studies is strongly enhanced by the availability of suitable systems of analysis. Such a system was identified in a series of radiation‐induced chromosomal deletions at and around the albino (c) locus of the mouse associated with cell type‐specific effects on liver differentiation. Their detailed study has aided the analysis of possible machanisms of cell type‐specific (...) gene expression. As summarized in this review, the experimental results strongly suggest that specific trans‐acting developmental regulatory genes are concerned with the differentiation of hormone‐inducible expression of a cluster of hepatocyte specific structural genes mapping in different parts of the genome. (shrink)

We have achieved a residue‐level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post‐translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to (...) date, systematic high‐throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure‐function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

PURPOSE:To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS:Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS:The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS:In a family (...) with autosomal dominant drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration. (shrink)

Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders dividing them into three categories depending (...) on the information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. (shrink)

Three recent genome‐wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120–180 in mice and (...) ∼100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression. (shrink)

There are a number of ways one could criticize the practice of patenting genes. This chapter argues that computer‐mediated expressions have revealed the false dichotomy in the law of intellectual property and that as new technologies emerge they will continue to pose problems for courts and innovators alike. This is because the range and nature of our expressions is increased with new technologies like computers, nanotechnology, and biotech. Genetic engineering and nanotechnology undermine the distinction between “clearly” patentable inventions and copyrightable (...) works of authorship. Persons carry obligations, rights, moral duties, and are the objects of almost all our ethical and legal considerations. Health care in general has improved to enable us to make more careful predictions about risks and to make choices with greater information. Useful scientific data have emerged from the various “mapping” projects seeking to reveal the intricacies of genomes and phenotypes. (shrink)

The explosion of multiomics data poses new challenges to existing data mining methods. Joint analysis of multiomics data can make the best of the complementary information that is provided by different types of data. Therefore, they can more accurately explore the biological mechanism of diseases. In this article, two forms of joint nonnegative matrix factorization based on the sparse and graph Laplacian regularization method are proposed. In the method, the graph regularization constraint can preserve the local geometric structure of data. (...) L 2,1 -norm regularization can enhance the sparsity among the rows and remove redundant features in the data. First, SG-jNMF1 projects multiomics data into a common subspace and applies the multiomics fusion characteristic matrix to mine the important information closely related to diseases. Second, multiomics data of the same disease are mapped into the common sample space by SG-jNMF2, and the cluster structures are detected clearly. Experimental results show that SG-jNMF can achieve significant improvement in sample clustering compared with existing joint analysis frameworks. SG-jNMF also effectively integrates multiomics data to identify co-differentially expressed genes. SG-jNMF provides an efficient integrative analysis method for mining the biological information hidden in heterogeneous multiomics data. (shrink)