Background DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples, 8 although one study that ma...Background DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples, 8 although one study that made use of a PCR-sequence-specific oligonucleotide (SSO) method did observe evidence of significant compatibility in the HLA-DQA1 and DQB1 alleles between patients and aborted fetuses. 9 This study was designed to investigate whether URSA were associated with particular DQ alleles or promoter alleles.Methods Thirty-two patients with URSA and 54 women who had had at least one successful pregnancy were included in this study. HLA-DQ genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DQB1 promoter was detected by the SSO and sequence-specific primer (SSP) methods. The DQA1, DQB1, and DQB1 promoter (QBP) gene frequencies in the patients were compared with the gene frequencies in normal controls. The data were analyzed statistically with the χ 2 and Fisher’s exact tests.Results The results showed that the frequency of DQB1 *0604/0605 was significantly higher and the frequency of DQB1 *0501/0502 was significantly lower in the patient group as compared with the normal controls. In addition, the frequencies of the DQA1 *01-DQB1 *0604/0605 and QBP6.2-DQB1 *0604/0605 haplotypes were overrepresented in the patients relative to the controls. Our results did not show any differences between URSA patients and the controls with regard to DQA1 and QBP allele frequencies. Conclusions Our data suggest that URSA is associated with the HLA-DQB1 coding region, and is not associated with its upstream regulatory region. The DQB1 *0604/0605, DQA1 *01-DQB1 *0604/0605, and QBP6.2-DQB1 *0604/0605 haplotypes may confer susceptibility to URSA, while the DQB1 *0501/0502 allele may protect women from URSA.展开更多
Chromatin accessibility is a highly informative structural feature for understanding gene transcription regulation,because it indicates the degree to which nuclear macromolecules such as proteins and RNAs can access c...Chromatin accessibility is a highly informative structural feature for understanding gene transcription regulation,because it indicates the degree to which nuclear macromolecules such as proteins and RNAs can access chromosomal DNA.Studies have shown that chromatin accessibility is highly dynamic during stress response,stimulus response,and developmental transition.Moreover,physical access to chromosomal DNA in eukaryotes is highly cell-specific.Therefore,current technologies such as DNase-seq,ATAC-seq,and FAIRE-seq reveal only a portion of the open chromatin regions(OCRs)present in a given species.Thus,the genome-wide distribution of OCRs remains unknown.In this study,we developed a bioinformatics tool called Char Plant for the de novo prediction of OCRs in plant genomes.To develop this tool,we constructed a three-layer convolutional neural network(CNN)and subsequently trained the CNN using DNase-seq and ATACseq datasets of four plant species.The model simultaneously learns the sequence motifs and regulatory logics,which are jointly used to determine DNA accessibility.All of these steps are integrated into Char Plant,which can be run using a simple command line.The results of data analysis using Char Plant in this study demonstrate its prediction power and computational efficiency.To our knowledge,Char Plant is the first de novo prediction tool that can identify potential OCRs in the whole genome.The source code of Char Plant and supporting files are freely available from https://github.com/Yin-Shen/Char Plant.展开更多
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 9870 775 )
文摘Background DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples, 8 although one study that made use of a PCR-sequence-specific oligonucleotide (SSO) method did observe evidence of significant compatibility in the HLA-DQA1 and DQB1 alleles between patients and aborted fetuses. 9 This study was designed to investigate whether URSA were associated with particular DQ alleles or promoter alleles.Methods Thirty-two patients with URSA and 54 women who had had at least one successful pregnancy were included in this study. HLA-DQ genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DQB1 promoter was detected by the SSO and sequence-specific primer (SSP) methods. The DQA1, DQB1, and DQB1 promoter (QBP) gene frequencies in the patients were compared with the gene frequencies in normal controls. The data were analyzed statistically with the χ 2 and Fisher’s exact tests.Results The results showed that the frequency of DQB1 *0604/0605 was significantly higher and the frequency of DQB1 *0501/0502 was significantly lower in the patient group as compared with the normal controls. In addition, the frequencies of the DQA1 *01-DQB1 *0604/0605 and QBP6.2-DQB1 *0604/0605 haplotypes were overrepresented in the patients relative to the controls. Our results did not show any differences between URSA patients and the controls with regard to DQA1 and QBP allele frequencies. Conclusions Our data suggest that URSA is associated with the HLA-DQB1 coding region, and is not associated with its upstream regulatory region. The DQB1 *0604/0605, DQA1 *01-DQB1 *0604/0605, and QBP6.2-DQB1 *0604/0605 haplotypes may confer susceptibility to URSA, while the DQB1 *0501/0502 allele may protect women from URSA.
基金supported by the National Natural Science Foundation of China(Grant No.31871269)the Hubei Provincial Natural Science Foundation of China(Grant No.2019CFA014)the Fundamental Research Funds for the Central Universities,China(Grant No.2662019PY069)。
文摘Chromatin accessibility is a highly informative structural feature for understanding gene transcription regulation,because it indicates the degree to which nuclear macromolecules such as proteins and RNAs can access chromosomal DNA.Studies have shown that chromatin accessibility is highly dynamic during stress response,stimulus response,and developmental transition.Moreover,physical access to chromosomal DNA in eukaryotes is highly cell-specific.Therefore,current technologies such as DNase-seq,ATAC-seq,and FAIRE-seq reveal only a portion of the open chromatin regions(OCRs)present in a given species.Thus,the genome-wide distribution of OCRs remains unknown.In this study,we developed a bioinformatics tool called Char Plant for the de novo prediction of OCRs in plant genomes.To develop this tool,we constructed a three-layer convolutional neural network(CNN)and subsequently trained the CNN using DNase-seq and ATACseq datasets of four plant species.The model simultaneously learns the sequence motifs and regulatory logics,which are jointly used to determine DNA accessibility.All of these steps are integrated into Char Plant,which can be run using a simple command line.The results of data analysis using Char Plant in this study demonstrate its prediction power and computational efficiency.To our knowledge,Char Plant is the first de novo prediction tool that can identify potential OCRs in the whole genome.The source code of Char Plant and supporting files are freely available from https://github.com/Yin-Shen/Char Plant.
