Project description:Interventions: Genomic test CANCERPLEX-JP OncoGuide NCC oncopanel system FndationONe CDx genome profile GUARDANT360 MSI Analysis System BRACAnalysis
Primary outcome(s): Development of genome database
Study Design: Single arm Non-randomized
Project description:The mammalian genome is spatially segregated into euchromatin-associated A and heterochromatin-associated B compartments that replicate early, and late in S-phase respectively. The molecular links connecting higher-order genome organization with replication timing, however, remain unclear. Here, we show that H2Bub (histone H2B lysine 120 monoubiquitination), a transcription-coupled epigenetic mark enriched over the gene body, regulates early replication. Furthermore, enforced recruitment of H2Bub promotes early replication in cis. Consistent with these observations, genetic ablation of RNF20, an E3 ubiquitin ligase that mediates H2Bub deposition, leads to reduced firing of early replication origins and suppression of cellular and embryonic growth. We also find a role of H2Bub for promoting proximal chromatin contacts at the gene body, and in gene rich A compartments, indicating that H2Bub may connect replication timing with higher-order genome organization. Surprisingly, H2Bub-marked regions in the genome coincide with SINEs (short interspersed nuclear elements). SINE retrotransposon enrichment in transcribed gene bodies correlates with H2Bub levels, indicating that these elements may direct H2Bub deposition at chromatin. Indeed, ectopic insertion of SINEs promotes local recruitment H2Bub. Taken together, our results suggest an unexpected role for SINE retrotransposons in linking higher-order genome organization with replication timing via targeting of the transcription-coupled epigenetic mark H2Bub.
Project description:The skin commensal yeast Malassezia is associated with several skin disorders. To establish a reference resource, we sought to determine the complete genome sequence of Malassezia sympodialis and identify its protein-coding genes. A novel genome annotation workflow combining RNA sequencing, proteomics, and manual curation was developed to determine gene structures with high accuracy.
Project description:<p>The section <em>Oleifera</em> (Theaceae) has attracted attention for the high levels of unsaturated fatty acids found in its seeds. Here, we report the chromosome-scale genome of the sect. <em>Oleifera</em> using diploid wild <em>Camellia lanceoleosa</em> with a final size of 3.00 Gb and an N50 scaffold size of 186.43 Mb. Repetitive sequences accounted for 80.63% and were distributed unevenly across the genome. <em>Camellia lanceoleosa</em> underwent a whole-genome duplication event approximately 65 million years ago (65 Mya), prior to the divergence of <em>C</em>. <em>lanceoleosa</em> and <em>Camellia sinensis</em> (approx. 6-7 Mya). Syntenic comparisons of these two species elucidated the genomic rearrangement, appearing to be driven in part by the activity of transposable elements. The expanded and positively selected genes in <em>C</em>. <em>lanceoleosa</em> were significantly enriched in oil biosynthesis, and the expansion of homomeric <em>acetyl-coenzyme A carboxylase</em> (<em>ACCase</em>) genes and the seed-biased expression of genes encoding heteromeric ACCase, diacylglycerol acyltransferase, glyceraldehyde-3-phosphate dehydrogenase and stearoyl-ACP desaturase could be of primary importance for the high oil and oleic acid content found in <em>C. lanceoleosa</em>. Theanine and catechins were present in the leaves of <em>C</em>. <em>lanceoleosa</em>. However, caffeine can not be dectected in the leaves but was abundant in the seeds and roots. The functional and transcriptional divergence of genes encoding SAM-dependent <em>N</em>-methyltransferases may be associated with caffeine accumulation and distribution. Gene expression profiles, structural composition and chromosomal location suggest that the late-acting self-incompatibility of <em>C. lanceoleosa</em> is likely to have favoured a novel mechanism co-occurring with gametophytic self-incompatibility. This study provides valuable resources for quantitative and qualitative improvements and genome assembly of polyploid plants in sect. <em>Oleifera</em>.</p>