Biology subjects

Wu, C.- t.

Publications and source records attributed to Wu, C.- t..

3 recordsLinked to original sources

bioRxiv2018

Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling

Chromosome structure is thought to be crucial for proper functioning of the nucleus. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. We begin by applying Oligopaint probes and the single-molecule localization microscopy methods of OligoSTORM and OligoDNA-PAINT to image 8 megabases of human chromosome 19, discovering that chromosomal regions contributing to compartments can form distinct structures. Intriguingly, our data also suggest that homologous maternal and paternal regions may be differentially organized. Finally, we integrate imaging data with Hi-C and restraint-based modeling using a method called integrative modeling of genomic regions (IMGR) to increase the genomic resolution of our traces to 10 kb.\n\nOne Sentence SummarySuper-resolution genome tracing, contact maps, and integrative modeling enable 10 kb resolution glimpses of chromosome folding.

genetics↗

bioRxiv2017

Ultraconserved elements occupy specific arenas of three-dimensional mammalian genome organization

This study explores the relationships between three-dimensional genome organization and the ultraconserved elements (UCEs), an enigmatic set of DNA elements that show very high DNA sequence conservation between vertebrate reference genomes. Examining both human and mouse genomes, we interrogate the relationship of UCEs to three features of chromosome organization derived from Hi-C studies. Firstly, we report that UCEs are enriched within contact domains and, further, that the UCEs that fall into domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither over- nor under-represented, with those present in loop anchors being enriched for splice sites compared to all UCEs. Finally, as all of the relationships we observed between UCEs and genomic features are conserved in the mouse genome, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.

genomics↗

bioRxiv2017

Structural disruption of genomic regions containing ultraconserved elements is associated with neurodevelopmental phenotypes

The development of the human brain and nervous system can be affected by genetic or environmental factors. Here we focus on characterizing the genetic perturbations that accompany and may contribute to neurodevelopmental phenotypes. Specifically, we examine two types of structural variants, namely, copy number variation and balanced chromosome rearrangements, discovered in subjects with neurodevelopmental disorders and related phenotypes. We find that a feature uniting these types of genetic aberrations is a proximity to ultraconserved elements (UCEs), which are sequences that are perfectly conserved between the reference genomes of distantly related species. In particular, while UCEs are generally depleted from copy number variant regions in healthy individuals, they are, on the whole, enriched in genomic regions disrupted by copy number variants or breakpoints of balanced rearrangements in affected individuals. Additionally, while genes associated with neurodevelopmental disorders are enriched in UCEs, this does not account for the excess of UCEs either in copy number variants or close to the breakpoints of balanced rearrangements in affected individuals. Indeed, our data are consistent with some manifestations of neurodevelopmental disorders resulting from a disruption of genome integrity in the vicinity of UCEs.

genomics↗