Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

SMC1A served as a potential therapeutic target to regulate malignant phenotypes of cervical cancer

Introduction:Structural maintenance of chromosome 1A(SMC1A)is a crucial compound of the cohesin complex.It has been reported to regulate the epithelial-mesenchymal transition(EMT)process in multiple cancers.Objectives:The present study aims to further clarify the role of SMC1A in cervical cancer.Methods:We analyzed data from four datasets and confirmed that SMC1A showed high expression in cervical cancer samples and was related to poor prognosis of patients with cervical cancer.Cell proliferation of SiHa and C-33A with knockdown of SMC1A was assessed using CCK-8 and colony formation assay.The migration and invasion were estimated by wound healing assay and Transwell assay separately.The effect of SMC1A on the chemosensitivity of cisplatin and paclitaxel in cervical cancer cells was detected by flow cytometry assay.Results:Results of the immunohistochemistry(IHC)assay confirmed that the expression of SMC1A was increased in tumor tissues.The cell viability was remarkably suppressed in SiHa and C-33A by knocking down the expression of SMC1A.The increase of E-cadherin expression and decrease of N-cadherin and Snail expression verified that inhibition of SMC1A suppressed the EMT process of cervical cancer cells.Further,cell migration,and invasion were significantly repressed by the absence of SMC1A.Cisplatin and paclitaxel are effective chemotherapeutic agents used in the treatment of cervical cancer.Silencing of SMC1A remarkably promoted the apoptosis induced by cisplatin and paclitaxel,revealing that the chemotherapy resistance to cisplatin and paclitaxel in cervical cancer could reduce by knocking down SMC1A.Further,metastasis associated with colon cancer 1(MACC1)was identified as the downstream factor of SMC1A.Its upregulation reversed the proliferation and the EMT process induced by SMC1A silencing.Conclusion:Therefore,our study concluded that SMC1A serves as a therapeutic molecular target to regulate the malignant phenotypes of cervical cancer.

Transcriptional Features of Cattle Visceral and Subcutaneous Adipose Tissues: A Study of RNA-seq

Visceral and subcutaneous are the two major types of bovine adipose tissues, and they show metabolic and functional differences according to their distribution, exploring the transcriptional features of visceral and subcutaneous adipose tissues is necessary. In the present study, we conducted RNA-seq analysis to compare the transcriptome between visceral (great omental) and subcutaneous (backfat) adipose tissues from Chinese Simmental cattle and validate them by qRT-PCR. We found that 5864 genes were differentially expressed between two tissues, including 2979 up-regulated and 2885 down-regulated in visceral adipose tissue. Functional analysis revealed a variety of differentially expressed genes (DEGs) involved in lipid metabolism and immune response processes. This may provide valuable information to further our understanding of the complexity of gene regulation governing the physiology of different fat depots. This work highlighted potential genes regulating lipid metabolism and immune responses;it may contribute to a better understanding of the metabolic and functional differences between visceral and subcutaneous adipose tissues.

Ancient origin and complex evolution of porcine endogenous retroviruses

Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in silico mined 14 pig genomes and other available 304 mammalian genomes,which led to the documentation of 185 full-length PERVs or PERV-like sequences.Notably,we found that lesser Egyptian jerboa(Jaculus jaculus),rock hyrax(Procavia capensis)and eight Muridae species all harbored ancestral PERV-like sequences,indicative of ancient cross-species transmission events from none-porcine species to pigs.We also revealed that 11 genomic rearrangement events were mediated via PERVs,during the process of porcine evolution.In conclusion,these new findings help us to understand the complex evolution of the modern PERVs.

Systematic Analysis of 42 Autographa Californica Multiple Nucleopolyhedrovirus Genes Identifies An Additional Six Genes Involved in the Production of Infectious Budded Virus

Baculoviruses have been widely used as a vector for expressing foreign genes.Among numerous baculoviruses,Autographa californica multiple nucleopolyhedrovirus(AcMNPV)is the most frequently used and it encodes 155 open reading frames(ORFs).Here,we systematically investigated the impact of 42 genes of AcMNPV on the production of infectious budded viruses(BVs)by constructing gene-knockout bacmids and subsequently conducting transfection and infection assays.The results showed that among the 39 functionally unverified genes and 3 recently reported genes,36 are dispensable for infectious BV production,as the one-step growth curves of the gene-knockout viruses were not significantly different from those of the parental virus.Three genes(ac62,ac82 and ac106/107)are essential for infectious BV production,as deletions thereof resulted in complete loss of infectivity while the repaired viruses showed no significant difference in comparison to the parental virus.In addition,three genes(ac13,ac51 and ac120)are important but not essential for infectious BV production,as gene-knockout viruses produced significantly lower BV levels than that of the parental virus or repaired viruses.We then grouped the 155 AcMNPV genes into three categories(Dispensable,Essential,or Important for infectious BV production).Based on our results and previous publications,we constructed a schematic diagram of a potential mini-genome of AcMNPV,which contains only essential and important genes.The results shed light on our understanding of functional genomics of baculoviruses and provide fundamental information for future engineering of baculovirus expression system.