scholarly journals A Cell Type-Specific Expression Signature Predicts Haploinsufficient Autism-Susceptibility Genes

2016 ◽  
Vol 38 (2) ◽  
pp. 204-215 ◽  
Author(s):  
Chaolin Zhang ◽  
Yufeng Shen
Keyword(s):  
Susceptibility Genes ◽  
Cell Type ◽  
Specific Expression ◽  
Expression Signature ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific ◽  
Autism Susceptibility

scholarly journals A cell type-specific expression signature predicts haploinsufficient autism-susceptibility genes

2016 ◽  
Author(s):  
Chaolin Zhang ◽  
Yufeng Shen
Keyword(s):  
Cortical Neurons ◽  
Expression Profiles ◽  
Susceptibility Genes ◽  
Large Sample Size ◽  
Cell Type ◽  
Specific Expression ◽  
Expression Signature ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Autism Susceptibility

AbstractRecent studies have identified many genes with rare de novo mutations in autism, but a limited number of these have been conclusively established as disease-susceptibility genes due to lack of recurrence and confounding background mutations. Such extreme genetic heterogeneity severely limits recurrence-based statistical power even in studies with a large sample size. In addition, the cellular contexts in which these genomic lesions confer disease risks remain poorly understood. Here we investigate the use of cell-type specific expression profiles to differentiate mutations in autism patients or unaffected siblings. Using 24 distinct cell types isolated from the mouse central nervous system, we identified an expression signature shared by genes with likely gene disrupting (LGD) mutations detected by exome-sequencing in autism cases. The signature reflects haploinsufficiency of risk genes enriched in transcriptional and post-transcriptional regulators, with the strongest positive associations with specific types of neurons in different brain regions, including cortical neurons, cerebellar granule cells, and striatal medium spiny neurons. Based on this signature, we assigned a D score to all human genes to prioritize candidate autism-susceptibility genes. When applied to genes with only a single LGD mutation in cases, the D score achieved a precision of 40% as compared to the 15% baseline with a minimal loss in sensitivity. Further improvement was made by combining D score and mutation intolerance metrics from ExAC which were derived from orthogonal data sources. The ensemble model achieved precision of 60% and predicted 117 high-priority candidates. These prioritized lists can facilitate identification of additional autism-susceptibility genes.

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Tissue- and Cell Type-Specific Expression of the Long Noncoding RNA Klhl14-AS in Mouse

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Sara Carmela Credendino ◽  
Nicole Lewin ◽  
Miriane de Oliveira ◽  
Swaraj Basu ◽  
Barbara D’Andrea ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Wide Spectrum ◽  
Functional Characterization ◽  
Cell Type ◽  
Specific Expression ◽  
Similar Expression Profile ◽  
Mouse Tissues ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific

lncRNAs are acquiring increasing relevance as regulators in a wide spectrum of biological processes. The extreme heterogeneity in the mechanisms of action of these molecules, however, makes them very difficult to study, especially regarding their molecular function. A novel lncRNA has been recently identified as the most enriched transcript in mouse developing thyroid. Due to its genomic localization antisense to the protein-encoding Klhl14 gene, we named it Klhl14-AS. In this paper, we highlight that mouse Klhl14-AS produces at least five splicing variants, some of which have not been previously described. Klhl14-AS is expressed with a peculiar pattern, characterized by diverse relative abundance of its isoforms in different mouse tissues. We examine the whole expression level of Klhl14-AS in a panel of adult mouse tissues, showing that it is expressed in the thyroid, lung, kidney, testis, ovary, brain, and spleen, although at different levels. In situ hybridization analysis reveals that, in the context of each organ, Klhl14-AS shows a cell type-specific expression. Interestingly, databases report a similar expression profile for human Klhl14-AS. Our observations suggest that this lncRNA could play cell type-specific roles in several organs and pave the way for functional characterization of this gene in appropriate biological contexts.

The role of CpG methylation in cell type-specific expression of the aquaporin-5 gene

2007 ◽  
Vol 353 (4) ◽  
pp. 1017-1022 ◽  
Author(s):  
Johji Nomura ◽  
Akinori Hisatsune ◽  
Takeshi Miyata ◽  
Yoichiro Isohama
Keyword(s):  
Cpg Methylation ◽  
Cell Type ◽  
Aquaporin 5 ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation

1992 ◽  
Vol 12 (2) ◽  
pp. 552-562
Author(s):  
L Pani ◽  
X B Quian ◽  
D Clevidence ◽  
R H Costa
Keyword(s):  
Transcription Factor ◽  
Promoter Activity ◽  
Binding Activity ◽  
Specific Factor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated alpha, beta, and gamma) possess homology in the DNA binding domain and in several additional regions. To understand the cell-type-specific expression of HNF-3 beta, we have defined the regulatory sequences that elicit hepatoma-specific expression. Promoter activity requires -134 bp of HNF-3 beta proximal sequences and binds four nuclear proteins, including two ubiquitous factors. One of these promoter sites interacts with a novel cell-specific factor, LF-H3 beta, whose binding activity correlates with the HNF-3 beta tissue expression pattern. Furthermore, there is a binding site for the HNF-3 protein within its own promoter, suggesting that an autoactivation mechanism is involved in the establishment of HNF-3 beta expression. We propose that both the LF-H3 beta and HNF-3 sites play an important role in the cell-type-specific expression of the HNF-3 beta transcription factor.

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