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The PNKD gene is associated with tourette disorder and tic disorder in a multiplex family

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Title
The PNKD gene is associated with tourette disorder and tic disorder in a multiplex family
Name (type = personal)
NamePart (type = family)
Sun
NamePart (type = given)
Nawei
NamePart (type = date)
1985-
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Nawei Sun
Role
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author
Name (type = personal)
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Firestein
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Bonnie L.
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Bonnie L. Firestein
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Advisory Committee
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chair
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Brzustowicz
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Linda
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Linda Brzustowicz
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Advisory Committee
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internal member
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Tischfield
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Jay A.
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Jay A. Tischfield
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Advisory Committee
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internal member
Name (type = personal)
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Heiman
NamePart (type = given)
Gary
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Gary Heiman
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Advisory Committee
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internal member
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Hart
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Ronald
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Ronald Hart
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Advisory Committee
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outside member
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Rutgers University
Role
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degree grantor
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NamePart
Graduate School - New Brunswick
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school
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Text
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theses
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2017
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2017-01
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2017
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xx
Language
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eng
Abstract (type = abstract)
Tourette Disorder (TD) is a highly heritable neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings have been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. In CHAPTER 1, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models, and importantly, review functional analyses that can be performed to evaluate the role(s) that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses, and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. In CHAPTER 2, we reported that a rare heterozygous nonsense mutation at the PNKD gene co-segregating with individuals affected by TD or Tic disorders in a multiplex family was identified by whole exome sequencing. Induced pluripotent stem cells (iPSCs) were generated from one unaffected and two TD affected individuals. Neurons were derived from the iPSCs and biochemical assays were conducted to evaluate possible molecular differences between affected and unaffected. We found that transcript and protein levels of the PNKD long isoform were reduced in neurons derived from the individuals with TD probably due to nonsense-mediated mRNA decay. Additionally, we demonstrated that the PNKD long protein monomer oligomerizes with itself as well as interacts the synaptic active zone protein RIMS1α. Therefore, we concluded that the reduction of the PNKD long protein in the neurons of TD patients in this multiplex family may contribute to TD.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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ETD_7824
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xi, 93 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Tourette syndrome
Subject (authority = ETD-LCSH)
Topic
Movement disorders--Genetic aspects
Note (type = statement of responsibility)
by Nawei Sun
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3251MNS
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
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Sun
GivenName
Nawei
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-01-05 13:06:04
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Name
Nawei Sun
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Affiliation
Rutgers University. Graduate School - New Brunswick
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License
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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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2019-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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