Dystrophin expression in heterozygous mdxl+ mice indicates imprinting of X chromosome inactivation by parent-of-origin-, tissue-, strain- and position-dependent factors

1997 ◽  
Vol 195 (2) ◽  
pp. 175-182 ◽  
Author(s):  
R. E. Bittner ◽  
Irene Popoff ◽  
Sigrid Shorny ◽  
Harald Höger ◽  
Franz Wachtler
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Tissue Strain ◽  
Dystrophin Expression ◽  
Parent Of Origin

scholarly journals A brain network basis of Fragile X syndrome behavioral penetrance determined by X chromosome inactivation in female mice

2018 ◽  
Author(s):  
Eric Szelenyi ◽  
Danielle Fisenne ◽  
Joseph E Knox ◽  
Julie A Harris ◽  
James A Gornet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Cell Density ◽  
X Chromosome ◽  
Fragile X ◽  
Mutant Cell ◽  
Autism Spectrum ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Entry Points ◽  
Parent Of Origin

ABSTRACTX-chromosome inactivation (XCI) in females is vital for normal brain function and cognition, as many X-linked genetic mutations lead to mental retardation and autism spectrum disorders, such as the fragile X syndrome (FXS). However, the degree by which XCI regulates disease presentation has been poorly investigated. To study this regulation in the mouse, here we quantified the brainwide composition of active-XC cells at single cell resolution using an X-linked MECP2-EGFP allele with known parent-of-origin. We present evidence that whole-brains, including all regions, on average favor maternal XC-active cells by 20%, or 8 million cells. This bias was conserved in heterozygous FXS mutant mice, which also corresponded to disease penetrance in maternal but not paternal FMR1 null mice. To localize the physical source of behavioral penetrance, brain-wide correlational screens successfully mapped mouse performance to cell densities in putative sensorimotor (e.g. sensory hindbrain, thalamus, globus pallidus) and sociability (e.g. visual/entorhinal cortices, bed nucleus stria terminalis, medial preoptic area) behavioral circuits of the open field sensorimotor and 3-chamber sociability assays, respectively. Overall, 50%/50% healthy/mutant cell density ratios in these sub-networks were required for disease presentation in each behavior. These results suggest female X-linked behavioral penetrance of disease is regulated at the distributed level of mutant cell density in behavioral circuits, which is set by XCI that is subject to parent-of-origin effects. This work provides a novel finding behind the broad and varied behavioral phenotypes commonly featured in female patients debilitated by X-linked mental disorders and may offer new entry points for behavioral therapeutics.

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

scholarly journals X-Linked Emery–Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation with Clinical Phenotypes in Female Carriers

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 919 ◽  
Author(s):  
Viggiano ◽  
Madej-Pilarczyk ◽  
Carboni ◽  
Picillo ◽  
Ergoli ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Fibrous Tissue ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Cardiac Conduction ◽  
Asymptomatic Carriers ◽  
Cardiac Symptoms ◽  
Female Carriers

X-linked Emery–Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers—25 familial and 5 sporadic cases—seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

scholarly journals Loss of p53 Causes Stochastic Aberrant X-Chromosome Inactivation and Female-Specific Neural Tube Defects

Cell Reports ◽  
2019 ◽  
Vol 27 (2) ◽  
pp. 442-454.e5 ◽  
Author(s):  
Alex R.D. Delbridge ◽  
Andrew J. Kueh ◽  
Francine Ke ◽  
Natasha M. Zamudio ◽  
Farrah El-Saafin ◽  
...  
Keyword(s):  
X Chromosome ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Specific

Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

2021 ◽  
Author(s):  
Bianca Pereira Favilla ◽  
Vera Ayres Meloni ◽  
Ana Beatriz Perez ◽  
Danilo Moretti‐Ferreira ◽  
Deise Helena Souza ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation

scholarly journals XChromosome Effect on Maternal Recombination and Meiotic Drive in the Mouse

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
Elena de la Casa-Esperón ◽  
J Concepción Loredo-Osti ◽  
Fernando Pardo-Manuel de Villena ◽  
Tammi L Briscoe ◽  
Jan Michel Malette ◽  
...  
Keyword(s):  
Mouse Chromosome ◽  
X Chromosome ◽  
Meiotic Recombination ◽  
Meiotic Drive ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome 11 ◽  
Genome Wide ◽  
Mouse Chromosome 11 ◽  
Segregation Of Chromosomes

AbstractWe observed that maternal meiotic drive favoring the inheritance of DDK alleles at the Om locus on mouse chromosome 11 was correlated with the X chromosome inactivation phenotype of (C57BL/ 6-Pgk1a × DDK)F1 mothers. The basis for this unexpected observation appears to lie in the well-documented effect of recombination on meiotic drive that results from nonrandom segregation of chromosomes. Our analysis of genome-wide levels of meiotic recombination in females that vary in their X-inactivation phenotype indicates that an allelic difference at an X-linked locus is responsible for modulating levels of recombination in oocytes.

scholarly journals X Chromosome Inactivation in Carriers of Fabry Disease: Review and Meta-Analysis

2021 ◽  
Vol 22 (14) ◽  
pp. 7663
Author(s):  
Emanuela Viggiano ◽  
Luisa Politano
Keyword(s):  
Fabry Disease ◽  
X Chromosome ◽  
Cardiac Involvement ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Corneal Dystrophy ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
The North ◽  
Kidney Involvement

Anderson-Fabry disease is an X-linked inborn error of glycosphingolipid catabolism caused by a deficiency of α-galactosidase A. The incidence ranges between 1: 40,000 and 1:117,000 of live male births. In Italy, an estimate of incidence is available only for the north-western Italy, where it is of approximately 1:4000. Clinical symptoms include angiokeratomas, corneal dystrophy, and neurological, cardiac and kidney involvement. The prevalence of symptomatic female carriers is about 70%, and in some cases, they can exhibit a severe phenotype. Previous studies suggest a correlation between skewed X chromosome inactivation and symptoms in carriers of X-linked disease, including Fabry disease. In this review, we briefly summarize the disease, focusing on the clinical symptoms of carriers and analysis of the studies so far published in regards to X chromosome inactivation pattern, and manifesting Fabry carriers. Out of 151 records identified, only five reported the correlation between the analysis of XCI in leukocytes and the related phenotype in Fabry carriers, in particular evaluating the Mainz Severity Score Index or cardiac involvement. The meta-analysis did not show any correlation between MSSI or cardiac involvement and skewed XCI, likely because the analysis of XCI in leukocytes is not useful for predicting the phenotype in Fabry carriers.

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