Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 13 of 13 for “"loss-of-function variants"”.
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Modelling fitness and stability of G protein-coupled receptor variants
… receptors (GPCRs) are the molecular targets of more than a third of approved drugs1 used in a wide variety of diseases2. Protein-altering genetic variants have complex effects on the biophysical and functional properties of GPCRs. Understanding the biophysical and functional effects of …
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Integrated approaches to elucidate the genetic architecture of congenital heart defects
… anomalies affecting the heart, are found in 1% of the population and arise during early stages of embryo development. Without surgical and medical interventions, most of the severe CHD cases would not survive after the first year of life. The improved health care for CHD patients has increased …
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Detection, causes and consequences of sex chromosome mosaicism
Sex chromosome mosaicism, including male mosaic loss of chromosome Y (LOY) and female mosaic loss of chromosome X (LOX), is the most common form of clonal haematopoiesis (CH) that can be defined as the age-related clonal expansion of blood cells with somatic mutations. With the decreased cost of …
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INTERNEURON TRANSPLANTS AS A TREATMENT FOR SEIZURES AND SOCIAL DEFICITS IN A MOUSE MODEL OF DRAVET SYNDROME
… deficits in several preclinical rodent models of epilepsy. These studies have generally focused on focal temporal epilepsy models, but less is understood about the efficacy of targeted interneuron transplants in epilepsy models caused by selective interneuron dysfunction, such as Dravet …
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Curation, characterisation and prediction of Drosophila signalling pathway members
… pathways are key to virtually every aspect of the biology of multicellular organisms. Extensive research in Drosophila melanogaster has greatly contributed to the understanding of these pathways, but a central resource distilling the vast literature on the topic has been lacking. At the same …
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The use of whole exome sequencing data to identify candidate genes involved in cancer and benign tumour predisposition
The development of whole exome sequencing has transformed the study of disease predisposition. The sequencing of both large disease sets and smaller rare disease families enables the identification of new predisposition variants and potentially provide clinical insight into disease management. …
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Molecular characterization in human neurons of genes associated with the control of bodyweight and feeding behaviour
… by increasingly abundant transcriptomic studies of murine and human hypothalamus – a brain area known to be a key regulator of food intake. The overarching aim of the project was to shed light on new appetitive control pathways and uncover new potential therapeutic targets to affect obesity. AgRP …
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Genetic and environmental modifiers of iron overload disease. Why do only some patients get serious health outcomes?
… and H63D genotypes. Haemochromatosis is one of the most common genetic conditions in populations of Northern European ancestry, with approximately 1 in 150 individuals carrying the high-risk C282Y homozygous genotype. However, its clinical expression is highly variable, and early symptoms …
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Genetic Determinants of Body Weight and Physical Maturation Across the Life Course
… points to early life as a critical period of heightened susceptibility to factors that alter the risk of later-life non-communicable diseases. Two early life risk factors increasingly recognised as important for adult health are early puberty timing and childhood obesity. Both factors are …
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Biased Constitutive Activity in the Uveal Melanoma Oncogene CYSLTR2 is Unique in CYSLTR2 Germline and Pan-Cancer Human Variome
… from skin cutaneous melanoma. In a subset of cases, the oncogenic driver is an activating mutation in CYSLTR2, the gene encoding the G protein-coupled receptor (GPCR) cysteinylleukotriene receptor 2. The mutant CYSLTR2 encodes for CysLTR2-L129Q receptor, with the substitution of Leu to Gln …
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Population-based genotype-phenotype correlation to stratify incident cases of motor neurone disease in Scotland from 2015-2017
… Motor neurone disease (MND) refers to a spectrum of rapidly progressive neurodegenerative diseases for which there remains no cure. A recognised and crucial barrier to more accurate diagnosis, prognosis and treatment relates to phenotypic heterogeneity. Recent discoveries in the genetic landscape …
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NOVEL INSIGHTS INTO GENETIC AND ENVIRONMENTAL DETERMINANTS SHAPING GNRH NEURON BIOLOGY AND RELATED REPRODUCTIVE DISORDERS
… neuroendocrine system essential for reproductive function in vertebrates. Central to this axis is the secretion of gonadotropin-releasing hormone (GnRH), a neuropeptide that stimulates the release of gonadotropins from the pituitary, driving gametogenesis and sex steroid production. GnRH-secreting …
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Genetic and functional studies in inherited platelet disorders
… and wound healing. Platelet number, volume, and function are genetically regulated, and genome wide association studies have identified more than 1000 loci associated with platelet traits. Common variants, with a minor allele frequency (MAF) ≥1% are associated with mild variation in platelet …