Clinical research on Angelman syndrome in the United Kingdom: Observations on 82 affected individuals

Clinical information has been obtained on 82 Angelman syndrome (AS) families in the UK. Each patient was examined by the author and a detailed clinical history taken. The findings of this study are presented. © 1993 Wiley-Liss, Inc.     

Genetic polymorphism of orosomucoid (ORM) in populations of the United Kingdom,Indian subcontinent,and Cambodia

Summary The genetic variation of the human serum orosomucoid (ORM) was investigated by isoelectric focusing (IEF) followed by immunofixation in 15 different populations from East Midlands (United Kingdom), India, Sri Lanka, and Cambodia. Statistically significant differences were observed between various Asiatic and British populations, however differences within Asiatic and European populations were minor. The distribution ofORM1 alleles in populations investigated to date suggests an interesting east-west geographical cline. There is a suggestion that present day wide polymorphism at theORM1 locus may be influenced by selection.     

Understanding and improving the experience of claiming social security for mental health problems in the west of Scotland: A participatory social welfare study

A growing body of literature links claimant interactions with the UK social security system and negative psychological consequences. Psychologists for social change developed a framework to outline proposed mechanisms of psychological impact from austerity. This codesigned study aimed to make an informed comment on areas of dis(agreement) between the Austerity Ailments framework and how people claiming for mental health problems describe their own experiences. In line with the participatory social welfare design of the study, qualitative analysis was performed by both claimants and academics. The overall findings indicate that existing framework mostly captured claimant experiences. However, some aspects of the claimant experience (particularly social aspects) were not well captured. Claimants were keen to utilise this study as an opportunity to gather claimant ideas on how to improve the system. Therefore, we report their suggestions that may be useful for those designing and improving social welfare systems     

Strategies for translational research in the United Kingdom

In the United Kingdom, many foundations and institutions and the government have made substantial investments in translational research. We examine the structures that surround this support and consider some of the results of this prodigious push toward enhancing translational research pursuits and thus improved clinical medicine.     

Suicidal function of DNA methylation in age-related genome disintegration

This article is dedicated to the 60th anniversary of 5-methylcytosine discovery in DNA. Cytosine methylation can affect genetic and epigenetic processes, works as a part of the genome-defense system and has mutagenic activity; however, the biological functions of this enzymatic modification are not well understood. This review will put forward the hypothesis that the host-defense role of DNA methylation in silencing and mutational destroying of retroviruses and other intragenomic parasites was extended during evolution to most host genes that have to be inactivated in differentiated somatic cells, where it acquired a new function in age-related self-destruction of the genome. The proposed model considers DNA methylation as the generator of 5mC > T transitions that induce 40–70% of all spontaneous somatic mutations of the multiple classes at CpG and CpNpG sites and flanking nucleotides in the p53, FIX, hprt, gpt human genes and some transgenes. The accumulation of 5mC-dependent mutations explains: global changes in the structure of the vertebrate genome throughout evolution; the loss of most 5mC from the DNA of various species over their lifespan and the Hayflick limit of normal cells; the polymorphism of methylation sites, including asymmetric mCpNpN sites; cyclical changes of methylation and demethylation in genes. The suicidal function of methylation may be a special genetic mechanism for increasing DNA damage and the programmed genome disintegration responsible for cell apoptosis and organism aging and death.     

Cytopathology in the United Kingdom: 1854 to the present

The paper traces the history of cytopathology in the U.K. from the time of the pioneers in the last century to the 1930s and continues with the development of cervical and breast screening, with reference to training and quality control, to the present time. Diagn. Cytopathol. 2000;22:203-206.     

Services to Bioengineering in the United Kingdom

In this paper, the resources available to the bioengineering profession are outlined. Information about the organisations that provide services to bioengineers, as well as indications as to how one might go about tapping them, is given.     

Bidirectional genomic exchange between Helicobacter pylori strains from a family in Coventry,United Kingdom

The human gastric pathogen Helicobacter pylori is characterised by a high mutation rate and frequent recombination during mixed infection, which result in extensive genetic diversity and rapid allelic diversification. Mixed infections are believed to be much more common in regions with a high H. pylori prevalence than in industrialised countries. To better understand the genomic flexibility of H. pylori in a low prevalence region, we used 454 sequencing technology to investigate whole genome sequences of H. pylori strains isolated from members of three generations of a family living in Coventry, UK. The genomes of four H. pylori strains isolated from a grandfather, two of his sons and one grandson were sequenced. Three of these genomes showed a high overall sequence similarity, suggesting a recent common ancestor. The genomes differed by 316–336 SNPs, and recombination events (imports) resulted in 170–251 clusters of polymorphisms (CNPs). Imports were particularly frequent in genes encoding Helicobacter outer membrane proteins, suggesting an adaptation of the strains to their individual host. The fourth strain differed substantially from these three highly related strains but still shared long fragments of identical sequence, which most likely reflect imports from the highly related family variants. The data show extensive bidirectional exchange of DNA between the strains isolated from the family members, illustrating both the convergence and divergence effect that recombination can lead to. Detailed analysis of the distribution of SNPs and imports permits to draw up a complex scenario of the transmission history involving infection with at least two, and probably more separate strains. This complexity and the resulting high frequency of recombination were unexpected for an industrialised country where the prevalence of H. pylori infection has strongly declined in recent decades.     

Comparative research on leukemia and related diseases: An introduction to a scientific approach

 Publication in this journal of the abstracts of the Nineteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases in Mannheim/Heidelberg led editor and publisher to suggest an article introducing comparative research in leukemia and related diseases. Our survey briefly summarizes the history of this symposium, as it evolved from a meeting on animal leukemia virus into one dealing with viral and genetic aspects of human and animal leukemia and related diseases. The scientific evolution of the Abelson murine leukemia virus with its abl oncogene in the 1970s to what currently appears as the most reliable marker for human chronic myeloid leukemia is merely one example.     

GISH technology in plant genome research

Genomic in situ hybridization, a modification of fluorescence in situ hybridization technology, is one of the most exciting and versatile research tools to be developed in recent years. It has enabled plant chromosome and genome research to progress at phenomenal rate and its potential is far from exhausted. Genomic in situ hybridization has applications in characterization of genomes and chromosomes in hybrid polyploids, hybrid plants, partial allopolyploids, polyhaploids and recombinant breeding lines; and in the localization, and detection of amount of introgressed alien chromatin. Genomic in situ hybridization has also given new insights into somaclonal variation, the origin of B chromosomes, control of chromosome pairing and other aspects of chromosome evolution. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field.     

SV40 DNA replication: From the A gene to a nanomachine

Duplication of the simian virus 40 (SV40) genome is the best understood eukaryotic DNA replication process to date. Like most prokaryotic genomes, the SV40 genome is a circular duplex DNA organized in a single replicon. This small viral genome, its association with host histones in nucleosomes, and its dependence on the host cell milieu for replication factors and precursors led to its adoption as a simple and powerful model. The steps in replication, the viral initiator, the host proteins, and their mechanisms of action were initially defined using a cell-free SV40 replication reaction. Although our understanding of the vastly more complex host replication fork is advancing, no eukaryotic replisome has yet been reconstituted and the SV40 paradigm remains a point of reference. This article reviews some of the milestones in the development of this paradigm and speculates on its potential utility to address unsolved questions in eukaryotic genome maintenance.     

The impact of human gene patents on genetic testing in the United Kingdom

PurposeThis article reports the results of an empirical study examining the impact of human gene patents on the development and delivery of genetic tests in the public sector in the United Kingdom.MethodsSemi-structured qualitative interviews.ResultsThe study found that, despite the potential for gene patents to have significant negative consequences for genetic testing, in fact, human gene patents have little or no impact on practice for those developing genetic tests in the public sector in the United Kingdom. This is not because patents are managed optimally; rather, gene patents are essentially ignored. This article reports the factors that motivate this behavior.ConclusionsAt least insofar as there seems to be no apparent problem of lack of patient access, there is no significant public health problem. However, there is divergence between the legal and the practical situation. Complacency about the lack of impact of patents on access to diagnostics is risky, and concerns about patents should be addressed proactively, rather than reactively. Genet Med 2011:13(4):320–324.     

From genome to proteome: developing expression clone resources for the human genome

Human Molecular Genetics (2006) 15,     

Newborn screening research sponsored by the NIH: From diagnostic paradigms to precision therapeutics

Newborn screening (NBS) is a successful public health initiative that effectively identifies pre-symptomatic neonates so that treatment can be initiated before the onset of irreversible morbidity and mortality. Legislation passed in 2008 has supported a system of state screening programs, educational resources, and an evidence-based review process to add conditions to a recommended universal newborn screening panel (RUSP). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, has promoted NBS research to advance legislative goals by supporting research that will uncover fundamental mechanisms of disease, develop treatments for NBS disorders, and promote pilot studies to test implementation of new conditions. NICHD's partnerships with other federal agencies have contributed to activities that support nominations of new conditions to the RUSP. The NIH's Newborn Sequencing In Genomic Medicine and Public Health (NSIGHT) initiative funded research projects that considered how genomic sequencing could be integrated into NBS and its ethical ramifications. Recently, the workshop, “Gene Targeted Therapies: Early Diagnosis and Equitable Delivery,” has explored the possibility of expanding NBS to include genetic diagnosis and precision, gene-based therapies. Although hurdles remain to realize such a vision, broad engagement of multiple stakeholders is essential to advance genomic medicine within NBS.     

Exchanging information: current United Kingdom developments in the infrastructure to support post-mortem imaging

Through joint working across the Home Office, Ministry of Justice and Department of Health the United Kingdom (UK) has developed a single programme of research and development in the field of less invasive autopsy, forensic and mass fatality imaging. By supporting research and development within these fields the UK has developed an outline for a national core training programme in this field along with the development of the National Forensic Image Management System (FiMag). This symposium paper is a brief overview of this development.