The biological function of lupus genetic dark matter has been revealed
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Last Update: 2021-01-13
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Source: Internet
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Author: User
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According to Shen Nan
SLE is a chronic autoimmune disease that is more common in women and can cause damage to multiple organs, and can be life-threatening, according to Professor
of the Institute of Rheumatology at Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine. However, the cause of the disease is unknown and there is currently no effective cure. Numerous studies have suggested that genetic and environmental factors are closely related to the occurrence of the disease, for example, in people with SLE disease, identical twins are far more likely to develop the disease than identical twins. Therefore, the study of the genomic function that determines genetics will help to reveal the pathogenesis of SLE and develop new prevention and treatment methods.
in the human genome, non-coding sequences account for 99%, but these non-coding sequences are not insequenced. Enhancers, for example, as part of a non-coding sequence, determine which cells a gene can express and the fate of cell differentiation. Interestingly, most of the genetic susceptible points of lupus found in the genetics are located in non-coding regions and in enhanced sub-regions. Based on these findings, the researchers speculate that disease susceptibility points located in enhanced subregions may act as a label for which disease susceptibility points in the genome are functional and which regulatory regions can participate in the development of SLE incidence.
this end, the researchers used genetics, oscloological histology, high-volume sequencing technology and other multi-group technology to determine the potential regulatory function of disease susceptibility points. At the same time, the use of 3D genomics, gene editing technology in the cell line, different generations of immune cells and humanized mice to edit the disease susceptible points, found that the gene-located rs2431697 is located in the enhancer through special dyeing Chromosome 3D structure in single-nucleocyte nate heterosexual participation in regulating miR-146a expression, and different allele differences affect the binding of transcription factors and chromosomal opening state, fine-tuning lupus disease-caused gene expression. More importantly, the researchers found that further importation of exostopic blood cells from lupus patients through crispr activation systems could target enhancers acting on the genetic susceptible site to specifically raise the level of miR-146a in monocytes, effectively blocking abnormal activation of interferon pathflytes in lupus patients.
experts say the study demonstrates a strategy for screening susceptibility points and functional regulatory elements for functional diseases, and linkes genetic variations in the risk of autoimmune diseases to the causes of autoimmune diseases, providing new directions and targets for the treatment of autoimmune diseases. (Source: Huang Xin, China Science Journal)
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