Project description:The rice field eel (Monopterus albus) is an economically important freshwater-farmed fish with natural sex reversal characteristics, which results in low egg production and seedling shortage. Limited epigenomic and transcriptomic information during sex reversal hinders research on the reproductive development of Monopterus albus. In this investigation, 9 key stages during sex reversal were collected for multi-omics experiments, including PacBio Iso-seq, RNA-seq and ATAC-seq. Through combined analysis of Iso-seq and RNA-seq, we constructed more accurate transcript annotation than those from NCBI. A total of 37,911 unannotated transcripts were obtained, including transcripts from novel genes and alternative splicing structures, etc. The noteworthy point is that our annotations have more precise polyA locations. In addition, we identified multiple potential cis-regulatory elements with high confidence based on changes in chromatin accessibility by ATAC-seq, providing precise targets for regulating gene expression and thereby modulating gonadal development. In summary, we provides a comprehensive and convenient data resource for studying sex reversal-related mechanisms from multiple perspectives.
Project description:The rice field eel (Monopterus albus) is an economically important freshwater-farmed fish with natural sex reversal characteristics, which results in low egg production and seedling shortage. Limited epigenomic and transcriptomic information during sex reversal hinders research on the reproductive development of Monopterus albus. In this investigation, 9 key stages during sex reversal were collected for multi-omics experiments, including PacBio Iso-seq, RNA-seq and ATAC-seq. Through combined analysis of Iso-seq and RNA-seq, we constructed more accurate transcript annotation than those from NCBI. A total of 37,911 unannotated transcripts were obtained, including transcripts from novel genes and alternative splicing structures, etc. The noteworthy point is that our annotations have more precise polyA locations. In addition, we identified multiple potential cis-regulatory elements with high confidence based on changes in chromatin accessibility by ATAC-seq, providing precise targets for regulating gene expression and thereby modulating gonadal development. In summary, we provides a comprehensive and convenient data resource for studying sex reversal-related mechanisms from multiple perspectives.
Project description:The rice field eel (Monopterus albus) is an economically important freshwater-farmed fish with natural sex reversal characteristics, which results in low egg production and seedling shortage. Limited epigenomic and transcriptomic information during sex reversal hinders research on the reproductive development of Monopterus albus. In this investigation, 9 key stages during sex reversal were collected for multi-omics experiments, including PacBio Iso-seq, RNA-seq and ATAC-seq. Through combined analysis of Iso-seq and RNA-seq, we constructed more accurate transcript annotation than those from NCBI. A total of 37,911 unannotated transcripts were obtained, including transcripts from novel genes and alternative splicing structures, etc. The noteworthy point is that our annotations have more precise polyA locations. In addition, we identified multiple potential cis-regulatory elements with high confidence based on changes in chromatin accessibility by ATAC-seq, providing precise targets for regulating gene expression and thereby modulating gonadal development. In summary, we provides a comprehensive and convenient data resource for studying sex reversal-related mechanisms from multiple perspectives.
Project description:This SuperSeries is composed of the following subset Series: GSE36822: Clonal competition with alternating dominance in multiple myeloma [244kCGH] GSE36823: Clonal competition with alternating dominance in multiple myeloma [44kCGH] GSE36824: Clonal competition with alternating dominance in multiple myeloma [GEP] Refer to individual Series
Project description:Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct a 140 kb int1h inversion frequently found in patients diagnosed with Hemophilia A. With the use of directed molecular evolution, we developed a linked heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from int1h patient derived iPSCs, resulted in prominent correction of the inversion and restored Factor VIII mRNA expression. Our data suggest that the development of designer-recombinases represent an efficient and specific mean towards treatment of large gene inversions causing monogenic diseases.
Project description:A growing list of metazoans undergo programmed DNA elimination (PDE), where a significant amount of DNA is selectively lost from the genome during development. In some nematodes, PDE leads to the removal of the ends of all germline chromosomes. In several species, PDE also eliminates sequences in the interior of the chromosomes, leading to an increased number of somatic chromosomes. The biological significance of these karyotype changes associated with PDE and the origin and evolution of nematode PDE remain largely unknown. Here, we assembled the single pair of germline chromosomes of the horse parasite Parascaris univalens and compared the karyotypes, gene organization within the chromosomes, and PDE features among ascarids. We show that Parascaris converts an XX/XY sex-determination system in the germline into an XX/XO system in the somatic cells. Comparisons of Ascaris, Parascaris, and Baylisascaris chromosomes suggest that PDE existed in the ancestor of these parasites, and their current distinct germline karyotypes were derived from fusion events of the same ancestral smaller chromosomes. PDE resolves these fused germline chromosomes and restores their pre-fusion karyotypes, leading to alterations in genome architecture and gene expression in the somatic cells. Cytological and genomic analyses further reveal the dynamic organization of the Parascaris germline chromosome during meiosis and a potential function for the satellite DNA and the heterochromatin arms. Overall, our results show that chromosome fusion and PDE have been harnessed in these ascarids to shape their karyotypes that could modulate the organization and functions of the genomes.
Project description:A growing list of metazoans undergo programmed DNA elimination (PDE), where a significant amount of DNA is selectively lost from the genome during development. In some nematodes, PDE leads to the removal of the ends of all germline chromosomes. In several species, PDE also eliminates sequences in the interior of the chromosomes, leading to an increased number of somatic chromosomes. The biological significance of these karyotype changes associated with PDE and the origin and evolution of nematode PDE remain largely unknown. Here, we assembled the single pair of germline chromosomes of the horse parasite Parascaris univalens and compared the karyotypes, gene organization within the chromosomes, and PDE features among ascarids. We show that Parascaris converts an XX/XY sex-determination system in the germline into an XX/XO system in the somatic cells. Comparisons of Ascaris, Parascaris, and Baylisascaris chromosomes suggest that PDE existed in the ancestor of these parasites, and their current distinct germline karyotypes were derived from fusion events of the same ancestral smaller chromosomes. PDE resolves these fused germline chromosomes and restores their pre-fusion karyotypes, leading to alterations in genome architecture and gene expression in the somatic cells. Cytological and genomic analyses further reveal the dynamic organization of the Parascaris germline chromosome during meiosis and a potential function for the satellite DNA and the heterochromatin arms. Overall, our results show that chromosome fusion and PDE have been harnessed in these ascarids to shape their karyotypes that could modulate the organization and functions of the genomes.