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- Title
Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novel Xce allele associated with copy number changes.
- Authors
Sun, Kathie Y.; Oreper, Daniel; Schoenrock, Sarah A.; McMullan, Rachel; Giusti-Rodríguez, Paola; Zhabotynsky, Vasyl; Miller, Darla R.; Tarantino, Lisa M.; Pardo-Manuel de Villena, Fernando; Valdar, William
- Abstract
Female 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 "Po' lya 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.
- Subjects
GENETICS; PHYLOGENY; ANIMAL experimentation; SEX chromosomes; ALLELES; GENETIC polymorphisms; FETAL development; CELL physiology; GENE expression profiling; HAPLOTYPES; PROBABILITY theory; MICE
- Publication
Genetics, 2021, Vol 218, Issue 1, p1
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1093/genetics/iyab034