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Regulatory Roles of Long Non-Coding RNA Genes in Cellular Identity and Complex Traits.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Regulatory Roles of Long Non-Coding RNA Genes in Cellular Identity and Complex Traits./
Author:	de Goede, Olivia M.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	168 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
Contained By:	Dissertations Abstracts International83-03B.
Subject:	Infections. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28688366
ISBN:	9798544203728

Regulatory Roles of Long Non-Coding RNA Genes in Cellular Identity and Complex Traits.
de Goede, Olivia M.

Regulatory Roles of Long Non-Coding RNA Genes in Cellular Identity and Complex Traits. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 168 p.

Source: Dissertations Abstracts International, Volume: 83-03, Section: B.

Thesis (Ph.D.)--Stanford University, 2021.

This item must not be sold to any third party vendors.

Genomic research primarily focuses on protein-coding genes, due to their obvious functional relevance and the well-defined relationships between DNA variation and protein sequence. However, most disease-associated variants are not in protein-coding sequences. This has led to much investigation of non-coding variation as it relates to protein-coding gene processing, but there is also a need to examine non-coding transcripts, and their roles in cellular function and trait outcomes. This dissertation contributes to the latter goal through studies of long non-coding RNA (lncRNA) genes, which are genes that produce RNAs >200 nucleotides long that are not translated into proteins. There are several examples of lncRNAs with key regulatory roles in processes such as dosage compensation (XIST), embryonic development (HOTAIR), and the immune response (NEAT1). However, it is still unclear how many lncRNA genes are functional, how many are byproducts of surrounding active gene expression, and how many are just transcriptional noise. The objective of this dissertation is to progress our understanding of non-coding genes through both broad analyses of the interplay between genetic variation and lncRNA expression patterns, followed by focused analyses of the involvement of candidate lncRNAs in immune response and other complex traits. In Chapter 2, I use the Genotype-Tissue Expression (GTEx) version 8 data to establish hallmarks of lncRNA gene expression and regulation and identify lncRNAs with robust complex trait associations. In Chapter 3, I examine the effects of the anti-inflammatory mouse lncRNA NeST on gene expression and chromatin accessibility in murine T cells. Finally, in Chapter 4, I profile lncRNA expression patterns in bulk purified immune cell populations, explore the regulatory patterns of the human NEST gene in these cell types, and evaluate this gene's possible relevance to autoimmune diseases. The findings and approaches described in this dissertation add to the existing annotation of functional lncRNA genes, and can help frame future studies of non-coding gene expression.

ISBN: 9798544203728Subjects--Topical Terms:

1621997
Infections.

Regulatory Roles of Long Non-Coding RNA Genes in Cellular Identity and Complex Traits.
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520 $a Genomic research primarily focuses on protein-coding genes, due to their obvious functional relevance and the well-defined relationships between DNA variation and protein sequence. However, most disease-associated variants are not in protein-coding sequences. This has led to much investigation of non-coding variation as it relates to protein-coding gene processing, but there is also a need to examine non-coding transcripts, and their roles in cellular function and trait outcomes. This dissertation contributes to the latter goal through studies of long non-coding RNA (lncRNA) genes, which are genes that produce RNAs >200 nucleotides long that are not translated into proteins. There are several examples of lncRNAs with key regulatory roles in processes such as dosage compensation (XIST), embryonic development (HOTAIR), and the immune response (NEAT1). However, it is still unclear how many lncRNA genes are functional, how many are byproducts of surrounding active gene expression, and how many are just transcriptional noise. The objective of this dissertation is to progress our understanding of non-coding genes through both broad analyses of the interplay between genetic variation and lncRNA expression patterns, followed by focused analyses of the involvement of candidate lncRNAs in immune response and other complex traits. In Chapter 2, I use the Genotype-Tissue Expression (GTEx) version 8 data to establish hallmarks of lncRNA gene expression and regulation and identify lncRNAs with robust complex trait associations. In Chapter 3, I examine the effects of the anti-inflammatory mouse lncRNA NeST on gene expression and chromatin accessibility in murine T cells. Finally, in Chapter 4, I profile lncRNA expression patterns in bulk purified immune cell populations, explore the regulatory patterns of the human NEST gene in these cell types, and evaluate this gene's possible relevance to autoimmune diseases. The findings and approaches described in this dissertation add to the existing annotation of functional lncRNA genes, and can help frame future studies of non-coding gene expression.
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