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Computational prediction and experimental verification of gene regulatory elements in neuronal development

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Computational prediction and experimental verification of gene regulatory elements in neuronal development
Identifier
ETD_2784
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056292
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biomedical Engineering
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Genetic regulation
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Electroporation
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Neurons--Growth
Abstract (type = abstract)
Completion of the human genome sequence along with other species allows for greater understanding of the biochemical mechanisms and processes that govern healthy as well as diseased states. Non-coding regions have been shown to play a critical role as gene regulatory elements. Enhancers that regulate transcription processes have been found in intergenic regions. Many regulatory elements found in non-coding regions are highly conserved across different species. While current sequence based computational methods are continuously improving in accuracy and scope, determining the time and tissue specific function of gene regulatory elements remain largely elusive. The goal of this dissertation is to identify novel gene regulatory elements involved in neuronal development using a combined approach which utilizes both computational prediction and experimental verification. We describe a method for utilizing genomes, annotations, computational tools, expression data, and molecular genetics methods to predict gene regulatory elements and confirm the function of these elements. In particular, the non-coding regions of homologous and functionally related genes are analyzed to identify highly conserved regions predicted to have gene regulatory function. To facilitate in the acquisition of desired sequences, a web tool was created to retrieve non-coding sequences based on annotations. Using multiple pair-wise alignments of non-coding sequence, over 502 conserved regions have been identified, at least 3 of which are well characterized, known enhancer elements. Previous studies utilized transgenic animals to experimental confirm the function of conserved regions. These animals are time consuming and expensive to generate. In contrast this study uses in ovo and in vivo electroporation of a plasmid DNA reporter construct for the confirmation of function. By transfecting the plasmid DNA reporter constructs into an animal model, enhancer function can be confirmed by the expression pattern of the reporter gene. Ten novel enhancers have been experimentally verified of which 2 have been characterized for the purpose of this study. Identification of novel gene regulatory elements allows for a better understanding of the mechanisms of gene regulation which may lead to the eventual control of gene expression. This has important implications and applications ranging from directing stem cell differentiation to designing new sequence based therapeutics.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
ix, 108 p. : ill.
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application/pdf
InternetMediaType
text/xml
Note
Supplementary File: Figure 1
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Supplementary File: Figure 23
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Supplementary File: Table 8
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Sung Tae Doh
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Doh
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Sung Tae
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1980-
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author
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Sung Tae Doh
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Cai
NamePart (type = given)
Li
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chair
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Advisory Committee
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Li Cai
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NamePart (type = family)
Androulakis
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Ioannis
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internal member
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Advisory Committee
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Ioannis Androulakis
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Kim
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Sobin
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internal member
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Advisory Committee
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Sobin Kim
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Rasin
NamePart (type = given)
Mladen-Roko
Role
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outside member
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Advisory Committee
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Mladen-Roko Rasin
Name (ID = NAME-6); (type = personal)
NamePart (type = family)
Xiang
NamePart (type = given)
Meng-qing
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Meng-qing Xiang
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010-10
Place
PlaceTerm (type = code)
xx
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3WD40B9
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Doh
GivenName
Sung Tae
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-07-21 17:00:31
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Sung Tae Doh
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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application/pdf
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application/x-tar
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