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GSE12454
Mus musculus
13 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.
Publication Title
The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation while Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching, and caused airway dilation similar to those seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be explained by the reduced expression of Shh in lung endoderm, a transcriptional target of YY1, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the critical requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.
Publication Title
Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
NextSeq 500
Description
10X-based scRNA-seq data human fetal kidneys at 5 different ages Overall design: w9, w11, w13, w16 and w18 human fetal kidneys
Publication Title
Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We report a highly-penetrant form of obesity, initially observed in 31 heterozygous carriers of a 593kb or larger deletion at 16p11.2 from amongst subjects ascertained for cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16053 individuals from 8 European cohorts; such deletions was absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (p = 6.4x10-8, OR = 43). These findings highlight a promising strategy for identifying missing heritability in obesity and other complex traits, in which insights from rare extreme cases can be used to elucidate the basis for more common phenotypes.
Publication Title
A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
Sample Metadata Fields
Specimen part, Disease
View Samples