Biology subjects

Raats, D.

Publications and source records attributed to Raats, D..

3 recordsLinked to original sources

bioRxiv2023

Pre-existing Subclones Determine Radioresistance in Rectal Cancer Organoids

More than half of all cancer patients receive radiation therapy, but resistance is commonly observed. Currently, it is unknown whether resistance to radiation therapy is acquired or inherently present. Here, we employed organoids derived from rectal cancer and single-cell whole genome sequencing to investigate the long-term evolution of subclones in response to radiation. Comparing single-cell whole genome karyotypes between unirradiated and irradiated organoids revealed three patterns of subclonal evolution: (i) subclonal persistence, (ii) subclonal extinction, and (iii) subclonal expansion. Only organoids in which subclonal shifts occurred (i.e., expansion or extinction) became more resistant to radiation. Although radioresistant subclones did not share recurrent copy number alterations that could explain their radioresistance, resistance was associated with reduced chromosomal instability; an association that was also observed in 529 human cancer cell lines. These data suggest resistance to radiation is inherently present and associated with reduced chromosomal instability.

cancer biology↗

bioRxiv2020

Three previously characterized resistances to yellow rust are encoded by a single locus Wtk1

The wild emmer wheat (Triticum turgidum ssp. dicoccoides; WEW) yellow (stripe) rust resistance genes Yr15, YrG303 and YrH52 were discovered in natural populations from different geographic locations. They all localize to chromosome 1B but were thought to be non-allelic based on differences in resistance response. We recently cloned Yr15 as a Wheat Tandem Kinase 1 (WTK1) and showed here that these three resistance loci co-segregate in fine-mapping populations and share identical full-length genomic sequence of functional Wtk1. Independent EMS mutagenized susceptible yrG303 and yrH52 lines carried single nucleotide mutations in Wtk1 that disrupted function. A comparison of the mutations for yr15, yrG303 and yrH52 mutants showed that while key conserved residues were intact, other conserved regions in critical kinase subdomains were frequently affected. Thus, we concluded that Yr15-, YrG303- and YrH52-mediated resistances to yellow rust are encoded by a single locus Wtk1. Introgression of Wtk1 into multiple genetic backgrounds resulted in variable phenotypic responses, confirming that Wtk1-mediated resistance is part of a complex immune response network. WEW natural populations subjected to natural selection and adaptation have potential to serve as a good source for evolutionary studies of different traits and multifaceted gene networks. HighlightWe demonstrate that Yr15, YrG303 and YrH52 resistances are encoded by the Wtk1 locus, but express variable resistance responses to yellow rust in a genetic background dependent manner.

genetics↗

bioRxiv2016

An improved assembly and annotation of the allohexaploid wheat genome identifies complete families of agronomic genes and provides genomic evidence for chromosomal translocations.

Advances in genome sequencing and assembly technologies are generating many high quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimised data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents more than 78% of the genome with a scaffold N50 of 88.8kbp that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNAseq and PacBio full-length cDNAs to identify 104,091 high confidence protein-coding genes and 10,156 non-coding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop. [Supplemental material is available for this article.]

genomics↗