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RM700Trio

ABSTRACT: Arthrogryposis multiplex congenita in a family of Red cattle

PROVIDER: PRJEB12094 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR1189163.fastq.gz	Fastqsanger.gz
	ERR1189163_1.fastq.gz	Fastqsanger.gz
	ERR1189163_2.fastq.gz	Fastqsanger.gz
	ERR1189164.fastq.gz	Fastqsanger.gz
	ERR1189164_1.fastq.gz	Fastqsanger.gz

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Project description:Background: Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome caused a group of genetic diseases called ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). Patients displayed arthrogryposis multiplex congenita (AMC), central and peripheral nervous system involvement, as well as multiple dysmorphic features. The underlying mechanisms of the complex syndrome remain to be elucidated. Methods: Expression levels of ZC4H2 were knockdown in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed shRNAs against ZC4H2. RNA sequencing (RNA seq) was subsequently applied to study the effects on gene expression profiles. The expression levels of differentially expressed genes were then verified by PCR array and RT-qPCR. Results: neural stem cell-like cells were induced from human induced pluripotent stem cells (hiPSCs), which were confirmed to express biomarkers of Neural stem cells (NSCs) by immunofluorescence. The viability of NSCs were affected through inhibition of ZC4H2 expression after they were infected with lentivirus containing siRNA targeting to ZC4H2 gene. The RNA-seq results showed that the gene expression pattern in NSCs was changed after inhibition of ZC4H2. DEGs were significantly enriched in oxidative phosphorylation and neurodegenerative diseases signaling pathways. Down-regulation of ZC4H2 might affect neural development by affecting the expression of genes related to oxidative phosphorylation signaling pathway. Conclusions: Down-regulation of genes related to the oxidative phosphorylation pathway might be involved in the pathogenity of the disease. Keywords: Female-restricted Wieacker-Wolff Syndrome (WRWF), Wieacker-Wolff Syndrome (WRWFFR), ZC4H2, Arthrogryposis multiplex congenita (AMC), nonsense mutation

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