scholarly journals ATR16 Syndrome: Mechanisms Linking Monosomy to Phenotype

2019 ◽  
Author(s):  
Christian Babbs ◽  
Jill Brown ◽  
Sharon W. Horsley ◽  
Joanne Slater ◽  
Evie Maifoshie ◽  
...  
Keyword(s):  
Genetic Background ◽  
Position Effect ◽  
Distal Region ◽  
Copy Number Variations ◽  
Chromosome 16 ◽  
Developmental Abnormalities ◽  
Telomere Position Effect ◽  
Wide Range ◽  
Genetic Background Effects ◽  
Critical Regions

AbstractBackgroundSporadic deletions removing 100s-1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual’s clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 34 patients with simple deletions of ∼177 to ∼2000 kb affecting one allele of the well characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised precise deletion extent and screened for genetic background effects, telomere position effect and compensatory up regulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller terminal chromosome 16 deletions (∼400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes, however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by sporadic copy number variations, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but also depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling.

scholarly journals ATR-16 syndrome: mechanisms linking monosomy to phenotype

2020 ◽  
Vol 57 (6) ◽  
pp. 414-421 ◽  
Author(s):  
Christian Babbs ◽  
Jill Brown ◽  
Sharon W Horsley ◽  
Joanne Slater ◽  
Evie Maifoshie ◽  
...  
Keyword(s):  
Genetic Background ◽  
Position Effect ◽  
Distal Region ◽  
Chromosome 16 ◽  
Developmental Abnormalities ◽  
Telomere Position Effect ◽  
Contiguous Gene ◽  
Wide Range ◽  
Genetic Background Effects ◽  
Critical Regions

BackgroundDeletions removing 100s–1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual’s clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 41 patients with simple deletions of ~177 to ~2000 kb affecting one allele of the well-characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised deletion extents and screened for genetic background effects, telomere position effect and compensatory upregulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller distal chromosome 16 deletions (~400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes; however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by CNVs, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling.

scholarly journals Polymorphic Iterable Sequential Effect Systems

2021 ◽  
Vol 43 (1) ◽  
pp. 1-79
Author(s):  
Colin S. Gordon
Keyword(s):  
Algebraic Structure ◽  
Position Effect ◽  
Type Systems ◽  
Sequential Effect ◽  
Prior Work ◽  
Sequential Effects ◽  
Wide Range ◽  
The Relationship ◽  
Categorical Semantics

Effect systems are lightweight extensions to type systems that can verify a wide range of important properties with modest developer burden. But our general understanding of effect systems is limited primarily to systems where the order of effects is irrelevant. Understanding such systems in terms of a semilattice of effects grounds understanding of the essential issues and provides guidance when designing new effect systems. By contrast, sequential effect systems—where the order of effects is important—lack an established algebraic structure on effects. We present an abstract polymorphic effect system parameterized by an effect quantale—an algebraic structure with well-defined properties that can model the effects of a range of existing sequential effect systems. We define effect quantales, derive useful properties, and show how they cleanly model a variety of known sequential effect systems. We show that for most effect quantales, there is an induced notion of iterating a sequential effect; that for systems we consider the derived iteration agrees with the manually designed iteration operators in prior work; and that this induced notion of iteration is as precise as possible when defined. We also position effect quantales with respect to work on categorical semantics for sequential effect systems, clarifying the distinctions between these systems and our own in the course of giving a thorough survey of these frameworks. Our derived iteration construct should generalize to these semantic structures, addressing limitations of that work. Finally, we consider the relationship between sequential effects and Kleene Algebras, where the latter may be used as instances of the former.

scholarly journals Studies of Flows Through N-Sequential Orifices

1983 ◽  
Vol 105 (3) ◽  
pp. 297-302 ◽  
Author(s):  
R. C. Hendricks ◽  
T. T. Stetz
Keyword(s):  
Mass Flux ◽  
Critical Mass ◽  
Pressure Profile ◽  
Profile Data ◽  
Axial Pressure ◽  
Reduced Pressure ◽  
Wide Range ◽  
Good For ◽  
Critical Regions ◽  
Reduced Temperature

Critical mass flux and axial pressure profile data for fluid nitrogen are presented for N = 20, 15, 10, and 7 N-sequential-orifice-inlet configurations uniformly spaced at 15.5 cm. These data correlate well over a wide range in reduced temperature (0.7 < Tr, 0 < ambient) and reduced pressure (to Pr = 2) and are in general agreement with previous studies of one to four inlets. Experimental and theoretical agreement is good for liquid and gas critical mass flux, but inconclusive in the near-thermodynamic critical regions.

Diverse developmental mutants revealed in an activation-tagged population of poplarThis article is one of a selection of papers published on the Special Issue of Poplar Research in Canada.

2007 ◽  
Vol 85 (11) ◽  
pp. 1071-1081 ◽  
Author(s):  
Edward J. Harrison ◽  
Michael Bush ◽  
Jonathan M. Plett ◽  
Daniel P. McPhee ◽  
Robin Vitez ◽  
...  
Keyword(s):  
Large Scale ◽  
Insertional Mutagenesis ◽  
Hybrid Poplar ◽  
Activation Tagging ◽  
Developmental Abnormalities ◽  
Endogenous Gene ◽  
Developmental Mutants ◽  
Poplar Trees ◽  
Wide Range ◽  
Mutant Lines

We have produced the largest population of activation-tagged poplar trees to date, approximately 1800 independent lines, and report on phenotypes of interest that have been identified in tissue culture and greenhouse conditions. Activation tagging is an insertional mutagenesis technique that results in the dominant upregulation of an endogenous gene. A large-scale Agrobacterium -mediated transformation protocol was used to transform the pSKI074 activation-tagging vector into Populus tremula × Populus alba hybrid poplar. We have screened the first 1000 lines for developmental abnormalities and have a visible mutant frequency of 2.4%, with alterations in leaf and stem structure as well as overall stature. Most of the phenotypes represent new phenotypes that have not previously been identified in poplar and, in some cases, not in any other plant either. Molecular analysis of the T-DNA inserts of a subpopulation of mutant lines reveal both single and double T-DNA inserts with double inserts more common in lines with visible phenotypes. The broad range of developmental mutants identified in this pilot screen of the population reveals that it will be a valuable resource for gene discovery in poplar. The full value of this population will only be realized as we screen these lines for a wide range of phenotypes.

scholarly journals Genetic background effects on age-related hearing loss associated with Cdh23 variants in mice

2012 ◽  
Vol 283 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Kelly L. Kane ◽  
Chantal M. Longo-Guess ◽  
Leona H. Gagnon ◽  
Dalian Ding ◽  
Richard J. Salvi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genetic Background ◽  
Age Related ◽  
Genetic Background Effects ◽  
Age Related Hearing Loss

scholarly journals A Rare Case of a Symptomatic Tumor Found in the Groin Area: An Atypical Location Unexposed to the Known Causes

2015 ◽  
Vol 8 (3) ◽  
pp. 536-539
Author(s):  
Ellen Toyonaga ◽  
Hiroo Hata ◽  
Chihiro Nakayama ◽  
Erina Homma ◽  
Toshiyuki Miyashita ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Early Onset ◽  
Rare Case ◽  
Gorlin Syndrome ◽  
Developmental Abnormalities ◽  
Wide Range ◽  
First Onset ◽  
Hereditary Condition

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The syndrome consists of early-onset and/or multiple BCC. Herein we report a rare NBCCS case in which the first BCC onset occurred in the groin area. To the best of our knowledge, there have been no reports of first-onset BCC in the groin area in an NBCCS patient of any race.

scholarly journals The impact of genetic background and cell lineage on the level and pattern of gene expression in position effect variegation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Sidney H. Wang ◽  
Sarah C. R. Elgin
Keyword(s):  
Genetic Variants ◽  
Genetic Background ◽  
Position Effect ◽  
Cell Lineage ◽  
Inbred Lines ◽  
Position Effect Variegation ◽  
Fourth Chromosome ◽  
Heterochromatin Formation ◽  
Effect Variegation ◽  
The Impact

Abstract Background Chromatin-based transcriptional silencing is often described as a stochastic process, largely because of the mosaic expression observed in position effect variegation (PEV), where a euchromatic reporter gene is silenced in some cells as a consequence of juxtaposition with heterochromatin. High levels of variation in PEV phenotypes are commonly observed in reporter stocks. To ascertain whether background mutations are the major contributors to this variation, we asked how much of the variation is determined by genetic variants segregating in the population, examining both the level and pattern of expression using the fruit fly, Drosophila melanogaster, as the model. Results Using selective breeding of a fourth chromosome PEV reporter line, 39C-12, we isolated two inbred lines exhibiting contrasting degrees of variegation (A1: low expression, D1: high expression). Within each inbred population, remarkable similarity is observed in the degree of variegation: 90% of the variation between the two inbred lines in the degree of silencing can be explained by genotype. Further analyses suggest that this result reflects the combined effect of multiple independent trans-acting loci. While the initial observations are based on a PEV phenotype scored in the fly eye (hsp70-white reporter), similar degrees of silencing were observed using a beta-gal reporter scored across the whole fly. Further, the pattern of variegation becomes almost identical within each inbred line; significant pigment enrichment in the same quadrant of the eye was found for both A1 and D1 lines despite different degrees of expression. Conclusions The results indicate that background genetic variants play the major role in determining the variable degrees of PEV commonly observed in laboratory stocks. Interestingly, not only does the degree of variegation become consistent in inbred lines, the patterns of variegation also appear similar. Combining these observations with the spreading model for local heterochromatin formation, we propose an augmented stochastic model to describe PEV in which the genetic background drives the overall level of silencing, working with the cell lineage-specific regulatory environment to determine the on/off probability at the reporter locus in each cell. This model acknowledges cell type-specific events in the context of broader genetic impacts on heterochromatin formation.

Sign in / Sign up

Export Citation Format

Share Document