Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes

Here the authors characterize structural variations (SVs) in a cohort of individuals with complex genomic rearrangements, identifying breakpoints by employing short- and long-read genome sequencing and investigate their impact on gene expression and the three-dimensional chromatin architecture. They find breakpoints are enriched in inactive regions and can result in chromatin domain fusions.Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements

Continuous crossover from two dimensional to one dimensional electronic properties for metallic silicide nanowires

In a joint experimental and theoretical study on metallic TbSi2 nanowires, we observe a continuous crossover from a two-dimensional (2D) to a quasi-one-dimensional (1D) electronic structure by reduction of the nanowire width. The nanowires were grown by self-organization on vicinal Si(111) substrates denoted by the Miller indices (hhk). Their electronic structure was analyzed by angle-resolved photoemission spectroscopy (ARPES) and calculated using density functional theory (DFT). In ARPES, the TbSi2 nanowires show basically the 2D electronic structure of the TbSi2 film on planar Si(111) with an increasing momentum broadening for decreasing nanowire widths, consistent with Heisenberg's uncertainty principle. In contrast, DFT calculations predict a purely 1D electronic structure for TbSi2 nanowires. Unfolding this 1D electronic structure onto the Brillouin zone of the TbSi2 film leads to a Fermi surface appearing similar to the one of the 2D TbSi2 film, but with an additional 1D contribution from nanowire edges. Such an additional 1D signature is also observed in ARPES for narrow nanowires. These results indicate a continuous transition to a 1D electronic structure for decreasing nanowire widths