Project description:BackgroundSilver arowana (Osteoglossum bicirrhosum) is a basal fish species with sexual monomorphism, while its sex determination mechanism has been poorly understood, posing a significant challenge to its captive breeding efforts.ResultsWe constructed two high-quality chromosome-level genome assemblies for both female and male silver arowana, with scaffold N50 values over 10 Mb. Combining re-sequencing data of 109 individuals, we identified a female-specific region, which was localized in a non-coding region, i.e., around 26-kb upstream of foxl2 gene (encoding forkhead box L2). Its strong interaction with the neighboring foxl2 on the same chromosome suggests foxl2 as a candidate sex-related gene in silver arowana. We subsequently propose a complex gene network in the sex determination process of silver arowana, with foxl2 acting as the central contributor. Transcriptome sequencing of gonads support our hypothesis that the regulation of foxl2 can be influenced by the spatial proximity of the female-specific fragment, thereby promoting ovarian function or inhibiting testicular function to stimulate gonadal differentiation. Furthermore, we found the sex chromosomes to be homomorphic with a potentially recent origin, as a linkage disequilibrium analysis proved minor recombination suppression.ConclusionsThese results taken together serve as a crucial foundation for conducting extensive investigations on the evolution and differentiation of sex-determining mechanisms, as well as the emergence and development of sex chromosomes in various fishes.
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:The South American arowanas (Osteoglossiformes, Osteoglossidae, Osteoglossum) are emblematic species widely distributed in the Amazon and surrounding basins. Arowana species are under strong anthropogenic pressure as they are extensively exploited for ornamental and food purposes. Until now, limited genetic and cytogenetic information has been available, with only a few studies reporting to their genetic diversity and population structure. In the present study, cytogenetic and DArTseq-derived single nucleotide polymorphism (SNP) data were used to investigate the genetic diversity of the two Osteoglossum species, the silver arowana O. bicirrhosum, and the black arowana O. ferreirai. Both species differ in their 2n (with 2n = 54 and 56 for O. ferreirai and O. bicirrhosum, respectively) and in the composition and distribution of their repetitive DNA content, consistent with their taxonomic status as different species. Our genetic dataset was coupled with contemporary and paleogeographic niche modeling, to develop concurrent demographic models that were tested against each other with a deep learning approach in O. bicirrhosum. Our genetic results reveal that O. bicirrhosum colonized the Tocantins-Araguaia basin from the Amazon basin about one million years ago. In addition, we highlighted a higher genetic diversity of O. bicirrhosum in the Amazon populations in comparison to those from the Tocantins-Araguaia basin.
Project description:The naked mole-rat (NMR; Heterocephalus glaber) has recently gained considerable attention in the scientific community for its unique potential to unveil novel insights in the fields of medicine, biochemistry, and evolution. NMRs exhibit unique adaptations that include protracted fertility, cancer resistance, eusociality, and anoxia. This suite of adaptations is not found in other rodent species, suggesting that interrogating conserved and accelerated regions in the NMR genome will find regions of the NMR genome fundamental to their unique adaptations. However, the current NMR genome assembly has limits that make studying structural variations, heterozygosity, and non-coding adaptations challenging. We present a complete diploid naked-mole rat genome assembly by integrating long-read and 10X-linked read genome sequencing of a male NMR and its parents, and Hi-C sequencing in the NMR hypothalamus (N=2). Reads were identified as maternal, paternal or ambiguous (TrioCanu). We then polished genomes with Flye, Racon and Medaka. Assemblies were then scaffolded using the following tools in order: Scaff10X, Salsa2, 3d-DNA, Minimap2-alignment between assemblies, and the Juicebox Assembly Tools. We then subjected the assemblies to another round of polishing, including short-read polishing with Freebayes. We assembled the NMR mitochondrial genome with mitoVGP. Y chromosome contigs were identified by aligning male and female 10X linked reads to the paternal genome and finding male-biased contigs not present in the maternal genome. Contigs were assembled with publicly available male NMR Fibroblast Hi-C-seq data (SRR820318). Both assemblies have their sex chromosome haplotypes merged so that both assemblies have a high-quality X and Y chromosome. Finally, assemblies were evaluated with Quast, BUSCO, and Merqury, which all reported the base-pair quality and contiguity of both assemblies as high-quality. The assembly will next be annotated by Ensembl using public RNA-seq data from multiple tissues (SRP061363). Together, this assembly will provide a high-quality resource to the NMR and comparative genomics communities.