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 20 of 196 for “"missense"”.
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Clustering-Based Methods for Clinical Risk Prediction of Rare Missense Variants
… disease gene. However, there are many other missense variants identified in established disease genes which are more challenging to classify. Improving predictions of such variants has the potential to lead to clinically actionable solutions for individual patients. In this paper, we develop …
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Protein structural and functional consequences of missense mutations in the human cancer genome
… — to evaluate the phenotypical impact of cancer missense mutations in the entire human proteome. We detect interesting patterns and are able to distinguish to some extent the molecular mechanisms that each of the affected genes exert in cancer. Our observations allow us to identify candidate …
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Functional validation of human rare missense variants associated with body fat distribution and cardiometabolic risk
… the power of studies to confidently link rare missense (coding) variants with a range of phenotypes. In collaboration with colleagues in the MRC Epidemiology Unit in Cambridge, we recently identified rare missense variants in ALK7 (p.I195T and p.N150H), CALCRL (p.L87P), PLIN1 (p.L90P) and PDE3B …
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Evaluation of Select Publicly Available in Silico Methods for Predicting Functional Effects of Missense Mutations in the GALNS Gene
… is less than 30 years. More than 200 unique missense mutations have been identified in the GALNS gene, with effects ranging from no change in function (wild-type) to significant reduction in functional effect (severe forms of the disease). Using GALNS as the model gene, we evaluated the …
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The involvement of non-B DNA forming sequences in mediating missense mutations, micro-deletions and micro-insertions in human inherited disease
… and epigenetic marks in mediating germline missense and nonsense mutations, micro-deletions and micro-insertions causing human inherited disease and obtained from Human Gene Mutation Database (HGMD; http://www.hgmd.org) was studied in silico. A novel algorithm with a linear running time has …
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Computational Tools and Analyses for Improved Inference of Variant Effects
… With over 50% of clinically interpreted missense variants classified as “variants of uncertain significance” (VUSes), multiple approaches are needed to improve variant interpretation. Multiplexed assays of variant effect (MAVEs) can experimentally test nearly all possible missense …
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The nanomechanics of polycystin-1: A kidney mechanosensor
… which are targeted by many naturally occurring missense mutations. Nothing is known about the effects of these mutations on the biophysical properties of PKD domains. In addition, PC1 is expressed along the renal tubule, where it is exposed to a wide range of concentration of urea. Urea is known …
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Isoform-Specific Variant and Expression Analysis of Epigenetic Genes in Neurodevelopment and Disease
… Hospital, Reykjavík, Iceland Introduction Missense mutations in epigenetic machinery (EM) genes are frequently associated with neurodevelopmental disorders. Studying the isoform-specific distribution of pathogenic variants and the timing of isoform expression may reveal critical mechanisms …
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An investigation of proteoforms in health and disease using peptide-level readouts
… My thesis work focuses on two proteoform types: missense mutations and phosphorylation. In Chapter 2, I demonstrate the utility of pooled mass spectrometry (MS)-based assays to measure solubility and thermal stability of missense mutations. Using ten disease-causing mutants of the human …
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Modelling fitness and stability of G protein-coupled receptor variants
… could be improved by combining information from missense and loss-of-function variants. I found that 50% of genes in the GPCR superfamily have insufficient expected loss-of-function variants to be ranked in the top quintile of genes by the popular LOEUF metric for human gene essentiality, and …
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Mutation of SLC7A14 Causes Syndromic Hearing Loss
… functions were examined in knockin mice with the missense mutation SLC7A14-p.(Gly330Arg). ABR thresholds, but not DPOAE thresholds, were elevated in the knockin mice at 3.5 months. Additionally, RP patients with the homozygous SLC7A14-p.(Gly330Arg) missense mutation exhibited elevated hearing …
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Impact of Neurodevelopmental Disorder-Associated Clinical Variants on the Catalytic Activity of KMT5B
… in DNA repair and heterochromatin formation. Missense variants found in KMT5B cause a related neurodevelopmental disorder in which patients experience neurodevelopmental phenotypes like developmental delay (DD), intellectual deficits (ID), autism spectrum disorder (ASD), seizures, and motor …
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Functional analysis of KLF2 and its lymphoma-derived mutants
… truncation mutants and 8/10 lymphoma derived missense/ indel mutants showed a loss of NOTCH2 suppression. Interestingly, KLF2 C274Y, C279Y, H292Y, H296Y and S287P mutants displayed enhanced reporter activities, suggesting gain of function. Wild type KLF2 was also found to be capable of …
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Identification and Characterization of Rare Variants in Cholinergic Nicotinic Receptor Genes and their Contribution to Substance Dependence
… risk for nicotine dependence among carriers of missense variants at conserved residues in <italic>CHRNB4</italic> in African Americans and European Americans.</p><p>We next aimed to determine whether rare genetic variation in these genes influence risk for developing alcohol or cocaine …
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3-Methylcrotonyl-CoA: Carboxylase Mangel
… Ein Patient war compound-heterozygot für die Missense-Mutation S535F (1604C>T) und die Nonsense-Mutation V694X (2079delA) im MCCA Gen. Bei einem zweiten Patienten wurde S535F (1604C>T) heterozygot nachgewiesen. Ein Patient mit konsanguinen Eltern war homozygot für die Missense-Mutation S535F …
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Functional consequences of mutations in GRIN2A and GRIN2B associated with mental disorders
… assessment in heterologous systems: four missense mutations affecting residues in or near the subunit pore regions, all of which are associated with epilepsy and intellectual disability. To model the impact of gene disrupting mutations in GRIN2A, a preliminary analysis of the functional …
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P53R245W Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer
… <em>Trp53</em> mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in <em>Trp53</em> result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic …
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Assessing the Clinical Relevance of BRCA1 BRCT Domain Variants of Uncertain Significance
… to BRCA1’s BRCT domain to accurately predict missense VUS pathogenicity and stratify VUSs to prioritize for functional analyses like phosphopeptide binding assays. All BRCA1 BRCT missense variants were collected from the ClinVar database and were analyzed using 50 different in silico tools. …
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Integrated approaches to elucidate the genetic architecture of congenital heart defects
… six de novo loss-of-function and 13 de novo missense variants. Only one gene showed recurrent de novo mutations in NOTCH1, a well known CHD gene that has mostly been associated with left ventricle outflow tract malformations (LVOT). Besides NOTCH1, the de novo analysis identified several …
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In-vivo investigation of resveratrol as a preventive for radiation-induced acute myeloid leukemia
… mouse bone marrow cells. Loss of 1 PU.1 gene and missense mutation of the remaining allele leads to acute myeloid leukemia in CBA mice.
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