1,721,058 research outputs found
Ongoing challenges in the diagnosis of 11p15.5-associated imprinting disorders
No full textThe overgrowth disorder Beckwith–Wiedemann syndrome and the growth restriction disorder Silver–Russell syndrome have been described as ‘mirror’ syndromes, in both their clinical features and molecular causes. Clinically, their nonspecific features, focused around continuous variables of atypical growth, make it hard to set diagnostic thresholds that are pragmatic without potentially excluding some cases. Molecularly, both are imprinting disorders, classically associated with ‘opposite’ genetic and epigenetic changes to genes on chromosome 11p15, but both are associated with somatic mosaicism as well as an increasing range of alternative (epi)genetic changes to other genes, which make molecular diagnosis an increasingly complex process. In this Current Opinion, we explore how the understanding of Beckwith–Wiedemann syndrome and Silver–Russell syndrome has evolved in recent years, stretching the canonical ‘mirror’ designations in different ways for the two disorders and how this is changing clinical and molecular diagnosis. We suggest some possible directions of travel toward more timely and stratified diagnosis, so that patients can access the early interventions that are so critical for good outcome
Beyond the gene roundtable discussion
No full textThis virtual discussion between biomedical researchers and academics in the literary humanities took place in June–July 2013, through the medium of blog and email. The participants are Tim Spector (Genetic Epidemiology), Karen Temple (Medical Genetics), Angelique Richardson (Literary Studies), Deborah J.G. Mackay (Human Genetics) and Peter Garratt (Literary Studies). The conversation was initiated and convened by Mandy Bloomfield (Literary Studies). What develops in the course of the discussion is a sense of the ways in which biomedical researchers working on genetics are discovering new complexities with profound cultural and philosophical implications, whilst those working in the humanities are considering what those implications might be, but from a position on the edges of specialist scientific knowledge and modes of thinking. Perhaps inevitably, we sometimes find we are not speaking quite the same language. And this question of language – of metaphors, varieties of meaning, precision and indeterminacy – crops up time and again in this discussion. Perhaps it is in these frictive edges between disciplines that productive dialogue can happen, and we can learn from the differences between perspectives. For example, in this discussion the ‘nurture–nature’ dichotomy is interrogated in different ways, but with equivalent levels of reflective rigour, by researchers in the biomedical and humanities disciplines alike. What do we really mean by those terms? What are the historical components of this conceptual divide? Is it even possible to separate ‘nurture’ from ‘nature’? If a consensus emerges from this discussion, it is that current research in both the sciences and the humanities is blurring the distinctions between such dichotomous constructions as ‘nature vs. nurture’ in ways that are changing thinking and practices across the disciplines. Whether this takes us to a revaluation of Victorian understandings of organism and environment, or into ever-more complicated relationships between medical practitioners and their patients, we are, as one participant puts it, ‘in for an interesting time'
Human imprinting disorders: Principles, practice, problems and progress
No full textEpigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic ‘imprint’ of the parent from whom they were inherited.Imprinted genes are (as a general rule) expressed from one parental allele only. Some imprinted genes are critical regulators of growth and development, and thus disruption of their normal monoallelic expression causes congenital imprinting disorders, with clinical features impacting growth, development, behaviour and metabolism.Imprinting disorders as a group have characteristics that challenge diagnosis and management, including clinical and molecular heterogeneity, overlapping clinical features, somatic mosaicism, and multi-locus involvement. New insights into the biology and epigenomics of the early embryo offers new clues about the origin and importance of imprinting disorders
Genetic diagnosis of subfertility – the impact of meiosis and maternal effects
No full textDuring reproductive age, approximately one in seven couples are confronted with fertility problems. While the etiology is diverse, including infections, metabolic diseases, hormonal imbalances and iatrogenic effects, it is becoming increasingly clear that genetic factors have a significant contribution. Due to the complex nature of infertility which often hints at a multifactorial cause, the search for potentially causal gene mutations in idiopathic infertile couples has remained difficult. Idiopathic infertility patients with a suspicion of an underlying genetic cause can be expected to have mutations in genes which do not readily affect general health, but are only essential in certain processes connected to fertility. In this review, we specifically focus on genes involved in meiosis, a process which plays a pivotal role in fertility, and genes critical for maternal effect processes. We give an overview of genes which have been linked to infertility, as well as genes which are good candidates. Finally, we propose a phenotypic range in which we expect an optimal diagnostic yield of a meiotic/maternal effect gene panel
Clinical and molecular basis of transient neonatal diabetes mellitus in Brazilian children
No full textWe report a series of patients with transient neonatal diabetes mellitus (TNDM). Paternal uniparental isodisomy of chromosome 6 and heterozygous KCNJ11 and ABC88 mutation were the mutations found. This first reported series of Brazilian patients expands the geographical data on TNDM contributing to better understanding of its pathophysiology
Genetics, molar pregnancies and medieval ideas of monstrous births: the lump of flesh in the King of Tars
No full textThe medieval English romance The King of Tars gives an account of a birth of a lump of flesh. This has been considered as fantastic and monstrous in past literature, the horrific union of a Christian and Saracen. However, while the text certainly speaks to miscegenation, we propose that this lump of flesh is actually a hydatidiform mole. We trace the hydatidiform mole from antiquity, surrounding it with contextual medieval examples, from theology, history and medicine, that also describe abnormal births as lumps of flesh'. By discussing medieval ideas of monsters as a warning sign, we interpret the lump of flesh in terms of abnormal births, seed transmission, parental contribution and sin. Ideas of warning, blame and intervention present themselves as a response to moles both in medieval texts as well as in modern reactions to hydatidiform moles. We explore the epigenetics of hydatidiform moles and relate them to the medieval text. In The King of Tars, the fault for the lump of flesh could reside with either parent; we find that this is also the case in the genetic formation of the hydatidiform mole; we also argue that the epigenetics supports medieval theories of seed transmission.</p
Genomic imprinting disorders: lessons on how genome, epigenome and environment interact
Full text linkGenomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease. Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints. Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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