Search results for "Position effect"
showing 10 items of 16 documents
Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements.
2017
Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly …
Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developme…
2019
BackgroundBalanced chromosomal rearrangements associated with abnormal phenotype are rare events, but may be challenging for genetic counselling, since molecular characterisation of breakpoints is not performed routinely. We used next-generation sequencing to characterise breakpoints of balanced chromosomal rearrangements at the molecular level in patients with intellectual disability and/or congenital anomalies.MethodsBreakpoints were characterised by a paired-end low depth whole genome sequencing (WGS) strategy and validated by Sanger sequencing. Expression study of disrupted and neighbouring genes was performed by RT-qPCR from blood or lymphoblastoid cell line RNA.ResultsAmong the 55 pat…
The Sea Urchin sns5 Insulator Protects Retroviral Vectors From Chromosomal Position Effects by Maintaining Active Chromatin Structure
2009
Silencing and position-effect (PE) variegation (PEV), which is due to integration of viral vectors in heterochromatin regions, are considered significant obstacles to obtaining a consistent level of transgene expression in gene therapy. The inclusion of chromatin insulators into vectors has been proposed to counteract this position-dependent variegation of transgene expression. Here, we show that the sea urchin chromatin insulator, sns5, protects a recombinant gamma-retroviral vector from the negative influence of chromatin in erythroid milieu. This element increases the probability of vector expression at different chromosomal integration sites, which reduces both silencing and PEV. By chr…
The environmental Kuznets curve within European countries and sectors: greenhouse emission, production function and technology
2018
Based on the environmental Kuznets curve (EKC) hypothesis and the technological change and the environment literature, our original contribution consists in analysing within the decomposition model the direct and indirect influence of technological change as well as the energy mix on CO2 emissions. Focusing on the dirtiest sectors of 25 EU countries in the period 1997-2005 and considering the endogeneity issue, we estimate an adjusted EKC relationship comparing a single equation model (univariate model) with a simultaneous equations system (bivariate model). Following Lopez (J Environ Econ Manag 27:163-184, 1994), a second equation is introduced where per capita income is a positive functio…
De novo t(12;17)(p13.3;q21.3) translocation with a breakpoint near the 5' end of the HOXB gene cluster in a patient with developmental delay and skel…
2007
A boy with severe mental retardation, funnel chest, bell-shaped thorax, and hexadactyly of both feet was found to have a balanced de novo t(12;17)(p13.3;q21.3) translocation. FISH with BAC clones and long-range PCR products assessed in the human genome sequence localized the breakpoint on chromosome 17q21.3 to a 21-kb segment that lies <30 kb upstream of the HOXB gene cluster and immediately adjacent to the 3′ end of the TTLL6 gene. The breakpoint on chromosome 12 occurred within telomeric hexamer repeats and, therefore, is not likely to affect gene function directly. We propose that juxtaposition of the HOXB cluster to a repetitive DNA domain and/or separation from required cis-regulatory …
Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structu…
2009
We generated mutant alleles of Drosophila melanogaster in which expression of the linker histone H1 can be down-regulated over a wide range by RNAi. When the H1 protein level is reduced to ∼20% of the level in wild-type larvae, lethality occurs in the late larval – pupal stages of development. Here we show that H1 has an important function in gene regulation within or near heterochromatin. It is a strong dominant suppressor of position effect variegation (PEV). Similar to other suppressors of PEV, H1 is simultaneously involved in both the repression of euchromatic genes brought to the vicinity of pericentric heterochromatin and the activation of heterochromatic genes that depend on their pe…
The Sea Urchin sns5 Chromatin Insulator Improves the Likelihood of Lentiviral Vectors in Erythroid Milieu By Organizing an Independent Chromatin Doma…
2015
Abstract Retroviral vectors are currently the most suitable vehicles for therapeutic gene transfer in hematopoietic stem cells. However, these vectors are known to integrate rather randomly throughout the genome, suffering the so called chromosomal position effects (PE). Such a critical occurrence most probably depends upon the ability of heterochromatin to spread in the inserted vector sequences. Moreover, the use of transgenes imply genotoxicity effects, since the cis-regulatory sequences harbored by the vector can disturb the proper transcription of the resident genes neighboring the integration site, potentially leading to malignant transformation. Due to their enhancer blocker activity…
How Return Affects the Decision to Surrender a Savings Insurance Policy: Detailed Observations on the Reverse Disposition Effect
2020
The disposition effect has been widely studied in academia, while the reverse disposition effect observed in mutual funds has gained relatively little attention. This study examines the reverse disposition effect in detail by using policy-level data from a Finnish life insurer with a considerable sample size. The results show that the Finnish savings policies with a positive return have a surrender rate that is over 30 percent lower than that of policies with a negative return. Tax incentives and expected future returns do not seem to cause this reverse disposition effect directly. Salient information strengthens the reverse disposition effect, and higher policyholder age and surrender fees…
Maintenance of item and order information in verbal working memory
2017
International audience; Although verbal recall of item and order information is well-researched in short-term memory paradigms, there is relatively little research concerning item and order recall from working memory. The following study examined whether manipulating the opportunity for attentional refreshing and articulatory rehearsal in a complex span task differently affected the recall of item- and order-specific information of the memoranda. Five experiments varied the opportunity for articulatory rehearsal and attentional refreshing in a complex span task, but the type of recall was manipulated between experiments (item and order, order only, and item only recall). The results showed …
Temporal stability and representational distinctiveness: Key functions of orthographic working memory
2011
A primary goal of working memory research has been to understand the mechanisms that permit working memory systems to effectively maintain the identity and order of the elements held in memory for sufficient time as to allow for their selection and transfer to subsequent processing stages. Based on the performance of two individuals with acquired dysgraphia affecting orthographic working memory (WM; the graphemic buffer), we present evidence of two distinct and dissociable functions of orthographic WM. One function is responsible for maintaining the temporal stability of letters held in orthographic WM, while the other is responsible for maintaining their representational distinctiveness. T…