Walter Map was a twelfth-century courtier and royal servant. He was a prolific writer, but De Nugis Curialium is the only surviving work confidently attributed to him. The book is a collection of short stories and anecdotes about the court, religion and history. Map's references demonstrate that he read widely, not only biblical and theological works, but also classical authors such as Horace, Virgil, Ovid and Juvenal. The only surviving manuscript of the work is a fourteenth-century copy once belonging to (...) the monk John Wells of Ramsey Abbey. The Cambridge bibliographer M. R. James would have been attracted to the breadth of Map's referencing, and the author's light-hearted writing style which was intended to entertain. James' 1914 Oxford publication corrected the earlier work of Thomas Wright who published an edition for the Camden Society in 1850. (shrink)

Genome‐wide identification of transcription factor binding sites with the ChIP‐seq method is an extremely important scientific endeavor − one that should ideally be performed for every transcription factor in as many cell types as possible. A major hurdle on the way to this goal is the necessity for a specific, ChIP‐grade antibody for each transcription factor of interest, which is often not available. Here, we describe CETCh‐seq, a recently published method utilizing genome engineering with the CRISPR/Cas9 system (...) to circumvent the need for a specific antibody. Using the CETCh‐seq method, targeted genomic editing results in an epitope‐tagged transcription factor, which is recognized by a well‐characterized, standard antibody, efficacious for ChIP‐seq. We have used CETCh‐seq in human cancer cell lines as well as mouse embryonic stem cells. We find that roughly 60% of transcription factors tagged using CETCh‐seq produce a high quality ChIP‐seq map, a significant improvement over traditional antibody‐based methods. (shrink)

In the future, the Human Genome Project could eventually open the way to perhaps the determination of the complete wiling diagram of the human brain. This kind of progress may move neuroscience forward into the next level of understanding of human neurophysiology, development and behavior. The next crucial step would be to know, exactly what are the function of this genes, and why its lack or alteration causes a certain disease. Although, genomic has in some way contributed to almost (...) every aspects of neurobiology, the results are both significant and troubling.One of the areas, where HGP will contribute to neuroscience is the mapping of qualitative or complex traits. Complex traits like appearence, intelligence and personality are likely to be affected by hundreds or thousands of different genes, rather than one or a few. On the other hand, the complex organisms are not just the simple result of the sum of their genes, nor do genes alone build the different part of organism or influence behaviour by themselves. In spite of the wide variety of misunderstanding, misinterpretation or possible misusing of these new genetic information, this sort of research may eventually lead to useful practical medical results for humans. This information can contribute to work out therapies to treat learning and memory disorders, neurological disorders like Alzheimer's disease, afflicting more and more people in an increasingly ageing population. Genetics believe, there are 3000 to 4000 hereditary diseases. Gene therapy could one day cure some of them, but only when all the details of their genetic basis are known. Biomedicine in the next century will probably have a completely new role in society based on the beginnings inherent in the HGP.There is a general agreement, that modern neuroscience raises important ethical concerns that not have been adequately addressed either by scientists themselves or by the bioethics community. Some scientists interpreted the rapid progress in neuroscience as additional conformation for a materialist account of human nature, resulting in an attack on traditional belief systems. There is a clear tension between the widely held believes and the intellectual views of many scientists. (shrink)

The Human Genome Project is an expensive, ambitious, and controversial attempt to locate and map every one of the approximately 100,000 genes in the human body. If it works, and we are able, for instance, to identify markers for genetic diseases long before they develop, who will have the right to obtain such information? What will be the consequences for health care, health insurance, employability, and research priorities? And, more broadly, how will attitudes toward human differences be affected, morally (...) and socially, by the setting of a genetic “standard”? The compatibility of individual rights and genetic fairness is challenged by the technological possibilities of the future, making it difficult to create an agenda for a “just genetics.” Beginning with an account of the utopian dreams and authoritarian tendencies of historical eugenics movements, this book’s nine essays probe the potential social uses and abuses of detailed genetic information. Lucid and wide-ranging, these contributions will interest bioethicists, legal scholars, and policy makers. Essays: “The Genome Project and the Meaning of Difference,” Timothy F. Murphy “Eugenics and the Human Genome Project: Is the Past Prologue?,” Daniel J. Kevles “Handle with Care: Race, Class, and Genetics,” Arthur L. Caplan “Public Choices and Private Choices: Legal Regulation of Genetic Testing,” Lori B. Andrews “Rules for Gene Banks: Protecting Privacy in the Genetics Age,” George J. Annas “Use of Genetic Information by Private Insurers,” Robert J. Pokorski “The Genome Project, Individual Differences, and Just Health Care,” Norman Daniels “Just Genetics: A Problem Agenda,” Leonard M. Fleck “Justice and the Limitations of Genetic Knowledge,” Marc A. Lappé. (shrink)

We here review primary methods used in quantifying and mapping 5‐hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme‐based detection, and methods involving DNA‐enrichment strategies and the genome‐wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5‐methylcytosine (5mC) by ten‐eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown. We focus in particular on an ultrasensitive single‐molecule imaging technique (...) that can detect and quantify 5hmC from trace samples and thus offer information regarding the distance‐based relationship between 5hmC and 5mC when used in combination with fluorescence resonance energy transfer. (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)

Expectations are high around the world that more research on human genomic variation will improve the utility of “precision medicine” and help address population health disparities through “precision public health”. In large measure, these expectations rest on the premise that researchers will be able to share human DNA samples and genomic data freely and widely across the international scientific community. The human genomics community pioneered polices of early deposit of genomic research data into open databases to facilitate the exchange and (...) use of data during the mapping and sequencing of the human genome in the 1990s, and the success of those policies has made a... (shrink)

During the past decade, it has become apparent that it is within our grasp to understand fully the development and functioning of complex organisms. It is widely accepted that this undertaking must include the elucidation of the genetic blueprint – the genome sequence – of a number of model organisms. As a prelude to the determination of these sequences, clonebased physical maps of the genomes of a number of multicellular animals and plants are being constructed. Yeast artificial chromosome (YAC) (...) vectors, by virtue of their relatively unbiased cloning capabilities and capacity to carry large inserts, have come to play a central role in the construction of these maps. The application of YACs to the physical map of the Caenorhabditis elegans genome has enabled cosmid clone ‘islands’ to be linked together in an efficient manner. The long‐range continuity has improved the linkage between the genetic and physical maps, greatly increasing its utility. Since the genome can be represented by a relatively small number of YACs, it has been possible to make replica filters of genomically ordered YACs available to the community at large. (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 role of gene expression in evolutionary adaptation has been a subject of debate for over 40 years.cis‐regulation of transcription has been proposed to be the primary source of morphological novelty in evolution, though this is based on only a handful of examples. Recently the first genome‐wide studies of gene expression adaptation have been published, giving us an initial global view of this process. Systematic studies such as these will allow a number of key questions currently facing the (...) field of gene expression evolution to be addressed. (shrink)

Higher states of consciousness in which the human mind can transcend the boundaries of logic and reason are envisioned as natural to the experience and potential growth of every human being. So far they have been mostly monitored by electrophysiological methods. In this study we were particularly interested in discovering the molecular transcriptional basis of higher states of consciousness. In addition to phenomenological reports of meditators who participated in this study the generated higher states of consciousness were also EEG recorded. (...) We assessed the whole genome gene expression analysis of long-term meditators in four separate trials and detected significant differential gene expression in association with higher states of consciousness. The number of differently expressed genes as well as high proportion of genes themselves differed between meditators. Despite this, gene ontology enrichment analysis found significant biological and molecular processes shared among meditators’ higher state of consciousness. (shrink)

Madole & Harden's assertion that the effects derived from within-family genome-wide association studies (GWASs) and from randomized controlled trials (RCTs) are equivalent is misleading. GWASs are substantially more “non-unitary, non-uniform, and non-explanatory” than RCTs. While the within-family GWAS bring us closer to identifying genetic causes, whether it will change behavioral genetics into a causal science is an open question.

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)

The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC cytidine (...) deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. “clustered”) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome‐wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators. (shrink)

Polygenic scores (PGSs) have several limitations. They are confounded with environmental effects on behavior and cannot be used to study how mutations affect brain function and behavior. For this, mutations with large effects, which often arise in only one geographical population are needed. Genome-wide association studies (GWASs), commonly used for identifying mutations, have difficulty detecting these mutations. A strategy that overcomes this challenge is discussed.

Whether, and to what degree, do patents granted on human genes cast a shadow of uncertainty over genomics and its applications? Will owners of patents on individual genes or clusters of genes sue those performing whole-genome analyses on human samples for patent infringement? These are related questions that have haunted molecular diagnostics companies and services, coloring scientific, clinical, and business decisions. Can the profusion of whole-genome analysis methods proceed without fear of patent infringement liability?Whole-genome sequencing is proceeding (...) apace. Academic centers have been performing whole-genome and -exome sequencing in research for at least five years, and academic clinical laboratories with national reach have been doing sequencing for clinical applications for almost as long. Companies have also been offering WGS and WES as a clinical service for a few years now. So far as we know, no one has been sued for infringement of “gene patents” for performing WGS. (shrink)

We address Turkheimer’s argument that genome-wide association studies of behaviors and psychiatric traits will fail to produce coherent explanations. We distinguish two major sources of potential i...

The interactions between genetic and environmental risk factors contribute to the aetiology of complex human diseases. Genome‐wide association studies (GWAS) have revealed that most of the genetic variants associated with complex diseases are located in the non‐coding part of the genome, preferentially within enhancers. Enhancers are distal cis‐regulatory elements composed of clusters of transcription factors binding sites that positively regulate the expression of their target genes. The generation of genome‐wide maps for histone marks (e.g., H3K27ac), (...) chromatin accessibility and transcription factor and coactivator (e.g., p300) binding profiles have enabled the identification of enhancers across many human cell types and tissues. Nonetheless, the functional and pathological consequences of the majority of disease‐associated genetic variants located within enhancers seem to be rather minor under normal conditions, thus questioning their medical relevance. Here we propose that, due to the prevalence of enhancer redundancy, the pathological effects of many disease‐associated non‐coding genetic variants might be preferentially (or even only) manifested under environmental stress. (shrink)

RNA binding proteins (RBPs) are key factors for the regulation of gene expression by binding to cis elements, i.e. short sequence motifs in RNAs. Recent studies demonstrate that cooperative binding of multiple RBPs is important for the sequence‐specific recognition of RNA and thereby enables the regulation of diverse biological activities by a limited set of RBPs. Cross‐linking immuno‐precipitation (CLIP) and other recently developed high‐throughput methods provide comprehensive, genome‐wide maps of protein‐RNA interactions in the cell. Structural biology gives detailed (...) insights into molecular mechanisms and principles of RNA recognition by RBPs, but has so far focused on single RNA binding proteins and often on single RNA binding domains. The combination of high‐throughput methods and detailed structural biology studies is expected to greatly advance our understanding of the code for protein‐RNA recognition in gene regulation, as we review in this article. (shrink)

A recent analysis of the genomes of Darwin's finches revealed extensive interspecies allele sharing throughout the history of the radiation and identified a key locus responsible for morphological evolution in this group. The radiation of Darwin's finches on the Galápagos archipelago has long been regarded as an iconic study system for field ecology and evolutionary biology. Coupled with an extensive history of field work, these latest findings affirm the increasing acceptance of introgressive hybridization, or gene flow between species, as a (...) significant contributor to adaptive evolution. Here, we review and discuss these findings in relation to both classical work on Darwin's finches and contemporary work showing similar evolutionary signatures in other biological systems. The continued unification of genomic data with field biology promises to further elucidate the molecular basis of adaptation in Darwin's finches and well beyond. (shrink)

In this article we examine the “phenotype” concept in light of recent technological advances in Genome-Wide Association Studies . By observing the technology and its presuppositions, we put forward the thesis that at least in this case genotype and phenotype are effectively coidentifled one by means of the other. We suggest that the coidentiflcation of genotype-phenotype couples in expression-based GWAS also indicates a conceptual dependence, which we call “co-deñnition.” We note that viewing these terms as codeflned runs against (...) possible expectations, viz., that genotypes and phenotypes could ultimately be expressed independently from one another. In addition, the co-definition of genotypes and phenotypes in this context emphasizes the correlative character of both genotypes and phenotypes in GWAS. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative (...) configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative (...) configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a “layered” approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation.

The prelims comprise: Introduction Monster Mythology The Legal and Ethical Issues Raised by the Human Genome Project Strategies to Regulate Genetic Technology Where do we go from here? Acknowledgments.

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non‐coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals (...) and the in‐depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome‐editing techniques including CRISPR/Cas9. These approaches are also applicable to low‐frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. (shrink)

This paper investigates how environmental structure, given the innate properties of a population, affects the degree to which this population can adapt to the environment. The model we explore involves simple agents in a 2-d world which can sense a local food distribution and, as specified by their genomes, move to a new location and ingest the food there. Adaptation in this model consists of improving the genomic sensorimotor mapping so as to maximally exploit the environmental resources. We vary environmental (...) structure to see its specific effect on adaptive success. In our investigation, two properties of environmental structure, conditioned by the sensorimotor capacities of the agents, have emerged as significant factors in determining adaptive success: (1) the information content of the environment which quantifies the diversity of conditions sensed, and (2) the expected utility for optimal action. These correspond to the syntactic and pragmatic aspects of environmental information, respectively. We find that the ratio of expected utility to information content predicts adaptive success measured by population gain and information content alone predicts the fraction of ideal utility achieved. These quantitative methods and specific conclusions should aid in understanding the effects of environmental structure on evolutionary adaptation in a wide range of evolving systems, both artificial and natural. (shrink)

This paper has been prepared from the perspective of the ESRC Genomics Policy & Research Forum, which has the particular mandate of linking social science research on genomics with ongoing public and policy debates. It is intended as a contribution to discussions about the future agenda for social scientific analyses of genomics. Given its scope, this paper is necessarily painted with a broad brush. It is presented in the hope that it can serve both as a useful reference for those (...) less familiar with the themes and foci of UK-based social science research about genomics and, for those more engaged in the field, as a foundation for discussions about the future social sciences agenda in this area. This paper has four parts. The first identifies the boundaries of the topic. It is suggested that the boundaries of genomics are properly regarded by social scientists as soft rather than hard, and as encompassing far more than genomics as narrowly understood. In the second part, the UK context for social science research is briefly described before proceeding to part three, which offers a survey of the major areas and patterns of research. This is organised by reference to the themes of globalisation, governance and regulation, and refers to 129 current or recently completed projects (surveyed during the winter of 2005) that address these themes. Part four proposes some appropriate areas for future research, drawing on and advancing what has been achieved thus far. Social scientific analyses of the nature and consequences of genomic science, it is claimed, have been crucially framed by the institutionalising of non-scientific considerations under the heading of ELSA/elsi (Ethical, Legal and Social Aspects/implications). It is suggested that an understanding of the limitations and consequences of this framing provides a vital starting point in considering future research agendas. (shrink)

While the 1970's have been called the environmental years, the 1990's could be seen as the genome years. As the challenge to map and to sequence the human genome mobilized the scientific community, risks and benefits of information and uses that would derive from this project have also raised ethical issues at the international level. The particular interest of the 1997 UNESCO Declaration relies on the fact that it emphasizes both the scientific importance of genetics and the appropriate (...) reinforcement of human rights in this area. It considers the human genome, at least symbolically, as the common heritage of humanity. (shrink)

Genome editing, for instance by CRISPR-Cas, is a major advancement of the last 10 years in medicine but questions ethically our practices. In particular, human embryo heritable genome editing is a source of great controversy. We explored how this ethical question was debated in the literature from PubMed database, in a period of 4 years (2016–2020) around the announcement of the ‘CRISPR babies’ Chinese experiment in November 2018. We evaluated the weight of the arguments for and against this (...) topic, through an analysis of reviews published on this question. The most important arguments come from the technical perspective: safety issues and benefits, putative long-term effects on the future generations and the need to assess this aspect. Next, foreseeable clinical benefits and the alternatives to these methods are discussed. The number of people that would benefit from such techniques is also considered. However, social and anthropological issues are addressed in a more disparate way. Parenthood and desire for children are sometimes overlooked. Few authors mention social justice, stigmatisation and equality of access. Consent and information are more clearly addressed, as well as the question of the relationship between generations. Finally, the effects on the nature of humankind or human species are far from being consensual; the risks of enhancement, eugenics and transhumanism are raised. We conclude that the risks associated with the immaturity of the technique were at the forefront of the ethical debate on human embryo heritable genome editing. Their consequences were seen as more immediate and easier to handle than those of sociological or anthropological projections, which are more speculative in nature. (shrink)

The completion of the chimpanzee genome will greatly help us determine which genetic changes are unique to humanity. Chimpanzees are our closest living relative, and a recent study has made considerable progress towards decoding the genome of our sister taxon.1 Over 75,000 common chimpanzee (Pan troglodytes) bacterial artificial chromosome end sequences were aligned and mapped to the human genome. This study shows the remarkable genetic similarity (98.77%) between humans and chimpanzees, while highlighting intriguing areas of potential difference. (...) If we wish to understand the genetic basis of humankind, the completion of the chimpanzee genome deserves high priority. BioEssays 24:490–493, 2002. © 2002 Wiley Periodicals, Inc. (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 most enigmatic feature of polytene chromosomes is their banding pattern, the genetic organization of which has been a very attractive puzzle for many years. Recent genome‐wide protein mapping efforts have produced a wealth of data for the chromosome proteins of Drosophila cells. Based on their specific protein composition, the chromosomes comprise two types of bands, as well as interbands. These differ in terms of time of replication and specific types of proteins. The interbands are characterized by their (...) association with “active” chromatin proteins, nucleosome remodeling, and origin recognition complexes, and so they have three functions: acting as binding sites for RNA pol II, initiation of replication and nucleosome remodeling of short fragments of DNA. The borders and organization of the same band and interband regions are largely identical, irrespective of the cell type studied. This demonstrates that the banding pattern is a universal principle of the organization of interphase polytene and non‐polytene chromosomes.Editor's suggested further reading in BioEssaysCaught in the act: Rapid, symbiont‐driven evolution AbstractFunction and evolution of sex determination mechanisms, genes and pathways in insects Abstract. (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)

DNA copy number variation (CNV) represents a considerable source of human genetic diversity. Recently,1 a global map of copy number variation in the human genome has been drawn up which reveals not only the ubiquity but also the complexity of this type of variation. Thus, two human genomes may differ by more than 20 Mb and it is likely that the full extent of CNV still remains to be discovered. Nearly 3000 genes are associated with CNV. This high degree (...) of variability with regard to gene copy number between two individuals challenges definitions of normality. Many CNVs are located in regions of complex genomic structure and this currently limits the extent to which these variants can be genotyped by using tagging SNPs. However, some CNVs are already amenable to genome‐wide association studies so that their influence on human phenotypic diversity and disease susceptibility may soon be determined. BioEssays 29:311–313, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

In 1996, President Clinton offered a promissory vision for human genetics when he said: “I think it won't be too many years before parents will be able to go home from the hospital with their newborn babies with a genetic map in their hands that will tell them, here's what your child's future will likely be like.”The rapid evolution of genetic sequencing technologies has advanced that vision. In October 2006, the cost of sequencing an entire human genome was $10.4 (...) million; by 2014 the cost had decreased a thousand fold. The term next generation sequencing describes a variety of laboratory methods that allow efficient determination of the precise order of nucleotides in a DNA sequence. The papers in this issue of the Journal of Law, Medicine & Ethics focus on “clinical NGS,” which refers to rapid DNA sequencing using second-, third- and fourth-generation sequencing technologies to perform genome-wide sequencing of multiple genes or alleles for clinical prognostic, diagnostic, and therapeutic purposes. (shrink)