Title Information
Title
Observing the natural and heteromorphic organization of the human genome in nanoscale resolution
Type of Resource (primo)
dissertations
Name: Personal
Name Part
Horrell, Jeremy Christian
Role
Role Term: Text
creator
Name: Personal
Name Part
Neretti, Nicola
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Sedivy, John
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Larschan, Erica
Role
Role Term: Text
Reader
Name: Personal
Name Part
Freiman, Richard
Role
Role Term: Text
Reader
Name: Personal
Name Part
Creton, Robbert
Role
Role Term: Text
Reader
Name: Personal
Name Part
Nir, Guy
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. Department of Molecular Biology, Cell Biology and Biochemistry
Role
Role Term: Text
sponsor
Origin Information
Copyright Date
2022
Physical Description
Extent
xiv, 109 p.
digitalOrigin
born digital
Note: thesis
Thesis (Ph. D.)--Brown University, 2022
Genre (aat)
theses
Abstract
The human genome is organized in a hierarchical manner from higher order to lower order structures. At the highest level are chromosome territories that are each separated into functional transcriptionally active and transcriptionally non-active regions. These active, A, and non-active, B, regions are further segmented into self-interacting regions called topologically associating domains. These organizational features of the genome are conserved between almost all organisms. The detection of organization has relied on analysis of DNA sequences through chromosome conformation capture technology, most notably, HiC. The question remains, however, how these organizational structures occur in situ. The development of two technologies in genome targeting and microscopy has allowed for the interrogation of the 3-dimensional genome structure. Collectively, these technologies are known as OligoSTORM where the genome is targeted at super-resolution, beyond the diffraction limit of visible light. Here we use automated microfluidics and OligoSTORM to observe the genome of a human B-lymphocyte with chromosome territory, sub-compartment, and topologically associated domains (TAD) context at nano-scale resolution. This accomplished disambiguation of human homologs to reveal finite structural features that distinguish these homologs one from another in a TAD by TAD manner . In addition, a key finding was the observation of homolog "pairing," later termed homolog kissing, where we observed the close proximity of homologs in a somatic human cell type—to our know, the first in a mammalian cell.
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00859922")
Topic
Chromatin
Subject
Topic
nuclear architecture
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01763322")
Topic
High resolution imaging
Subject
Topic
3d fish
Subject
Topic
Oligopaints
Subject
Topic
stochastic optical reconstruction microscopy
Language
Language Term (ISO639-2B)
English
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20220706