scholarly journals Skewed X inactivation in genetically diverse mice is associated with recurrent copy number changes at the Xce locus

2020 ◽  
Author(s):  
Kathie Y Sun ◽  
Daniel Oreper ◽  
Sarah A Schoenrock ◽  
Rachel McMullan ◽  
Paola Giusti-Rodríguez ◽  
...  
Keyword(s):  
X Chromosome ◽  
Copy Number ◽  
Sequence Data ◽  
Large Population ◽  
Inbred Strains ◽  
Individual Variability ◽  
Urn Model ◽  
Allelic Series ◽  
Specific Expression ◽  
Copy Number Changes

ABSTRACTFemale mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176 kb candidate interval. A series of functional Xce alleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function-structure basis and location of the Xce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross strains. Using published sequence data and applying a Bayesian “Pólya urn” model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts on average contain 20-30 cells contributing to brain. Second, NOD/ShiLtJ has a novel and unique functional allele, Xcef, that is the weakest in the Xce allelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within the Xce. Copy number variation is common at the Xce locus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weak Xce alleles.

Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novelXceallele associated with copy number changes

Genetics ◽  
2021 ◽  
Author(s):  
Kathie Y Sun ◽  
Daniel Oreper ◽  
Sarah A Schoenrock ◽  
Rachel McMullan ◽  
Paola Giusti-Rodríguez ◽  
...  
Keyword(s):  
X Chromosome ◽  
Copy Number ◽  
Sequence Data ◽  
Large Population ◽  
Inbred Strains ◽  
Individual Variability ◽  
Urn Model ◽  
Allelic Series ◽  
Specific Expression ◽  
Copy Number Changes

AbstractFemale mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176-kb candidate interval. A series of functional Xce alleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function structure basis and location of the Xce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross (CC) strains. Using published sequence data and applying a Bayesian “Pólya urn” model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts contain on average 20–30 cells contributing to brain. Second, CC founder strain NOD/ShiLtJ has a novel and unique functional allele, Xceg, that is the weakest in the Xce allelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within the Xce. Copy number variation is common at the Xce locus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weak Xce alleles.

scholarly journals A Functional Chromatin Domain Does Not Resist X Chromosome Inactivation: Silencing of cLys Correlates with Methylation of a Dual Promoter-Replication Origin

2002 ◽  
Vol 22 (13) ◽  
pp. 4667-4676 ◽  
Author(s):  
Suyinn Chong ◽  
Joanna Kontaraki ◽  
Constanze Bonifer ◽  
Arthur D. Riggs
Keyword(s):  
X Chromosome ◽  
Copy Number ◽  
Cpg Island ◽  
Regulatory Elements ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromatin Domain ◽  
Specific Expression ◽  
Position Effects ◽  
Chicken Lysozyme

ABSTRACT To investigate the molecular mechanism(s) involved in the propagation and maintenance of X chromosome inactivation (XCI), the 21.4-kb chicken lysozyme (cLys) chromatin domain was inserted into the Hprt locus on the mouse X chromosome. The inserted fragment includes flanking matrix attachment regions (MARs), an origin of bidirectional replication (OBR), and all the cis-regulatory elements required for correct tissue-specific expression of cLys. It also contains a recently identified and widely expressed second gene, cGas41. The cLys domain is known to function as an autonomous unit resistant to chromosomal position effects, as evidenced by numerous transgenic mouse lines showing copy-number-dependent and development-specific expression of cLys in the myeloid lineage. We asked the questions whether this functional chromatin domain was resistant to XCI and whether the X inactivation signal could spread across an extended region of avian DNA. A generally useful method was devised to generate pure populations of macrophages with the transgene either on the active (Xa) or the inactive (Xi) chromosome. We found that (i) cLys and cGas41 are expressed normally from the Xa; (ii) the cLys chromatin domain, even when bracketed by MARs, is not resistant to XCI; (iii) transcription factors are excluded from lysozyme enhancers on the Xi; and (iv) inactivation correlates with methylation of a CpG island that is both an OBR and a promoter of the cGas41 gene.

scholarly journals Copy Number Changes on the X Chromosome in Women with and without Highly Skewed X-Chromosome Inactivation

2012 ◽  
Vol 136 (4) ◽  
pp. 264-269 ◽  
Author(s):  
V. Jobanputra ◽  
B. Levy ◽  
A. Kinney ◽  
S. Brown ◽  
M. Shirazi ◽  
...  
Keyword(s):  
X Chromosome ◽  
Copy Number ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Copy Number Changes ◽  
Skewed X Chromosome Inactivation

Screening of subtle copy number changes in Aicardi syndrome patients with a high resolution X chromosome array-CGH

2007 ◽  
Vol 50 (5) ◽  
pp. 386-391 ◽  
Author(s):  
Saliha Yilmaz ◽  
Hervé Fontaine ◽  
Karène Brochet ◽  
Marie-José Grégoire ◽  
Marie-Dominique Devignes ◽  
...  
Keyword(s):  
High Resolution ◽  
X Chromosome ◽  
Copy Number ◽  
Array Cgh ◽  
Aicardi Syndrome ◽  
Copy Number Changes

scholarly journals Copy number variant detection in inbred strains from short read sequence data

2009 ◽  
Vol 26 (4) ◽  
pp. 565-567 ◽  
Author(s):  
J. T. Simpson ◽  
R. E. McIntyre ◽  
D. J. Adams ◽  
R. Durbin
Keyword(s):  
Copy Number ◽  
Sequence Data ◽  
Copy Number Variant ◽  
Inbred Strains ◽  
Short Read ◽  
Short Read Sequence ◽  
Variant Detection ◽  
Copy Number Variant Detection

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%).

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

scholarly journals Whole-genome sequencing from the New Zealand Saccharomyces cerevisiae population reveals the genomic impacts of novel microbial range expansion

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Peter Higgins ◽  
Cooper A Grace ◽  
Soon A Lee ◽  
Matthew R Goddard
Keyword(s):  
Saccharomyces Cerevisiae ◽  
New Zealand ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Range Expansion ◽  
Copy Number ◽  
Small Scale ◽  
Whole Genome ◽  
Copy Number Changes ◽  
The Impact

Abstract Saccharomyces cerevisiae is extensively utilized for commercial fermentation, and is also an important biological model; however, its ecology has only recently begun to be understood. Through the use of whole-genome sequencing, the species has been characterized into a number of distinct subpopulations, defined by geographical ranges and industrial uses. Here, the whole-genome sequences of 104 New Zealand (NZ) S. cerevisiae strains, including 52 novel genomes, are analyzed alongside 450 published sequences derived from various global locations. The impact of S. cerevisiae novel range expansion into NZ was investigated and these analyses reveal the positioning of NZ strains as a subgroup to the predominantly European/wine clade. A number of genomic differences with the European group correlate with range expansion into NZ, including 18 highly enriched single-nucleotide polymorphism (SNPs) and novel Ty1/2 insertions. While it is not possible to categorically determine if any genetic differences are due to stochastic process or the operations of natural selection, we suggest that the observation of NZ-specific copy number increases of four sugar transporter genes in the HXT family may reasonably represent an adaptation in the NZ S. cerevisiae subpopulation, and this correlates with the observations of copy number changes during adaptation in small-scale experimental evolution studies.

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