Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"Vanderbilt University" +contributor:("John A. Phillips III"). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Vanderbilt University

1. Shariat, Nikki. Growth Hormone Splicing and Treatment of Disease Using RNA Interference.

Degree: PhD, Biological Sciences, 2008, Vanderbilt University

Splicing is the regulated removal of introns and the concurrent ligation of exons to produce mature mRNA transcripts. Variability in this tightly regulated process is responsible for an extraordinarily diverse proteome from a relatively small mammalian genome. Alternative splicing can lead to differential exon inclusion or exclusion, as can aberrant splicing, and such transcripts therefore differ from constitutively spliced transcripts. Where mistakes in splicing cause disease, the resulting mutant transcripts appear to be ideal targets for RNA interference (RNAi). In the case of inappropriate exon inclusion, small interfering RNAs (siRNAs) can be targeted to specific exons. When exon skipping prevails, siRNAs can be designed complementary to the specific exon-exon junctions that are not present in normal transcripts. The human growth hormone gene, GH-1, nicely illustrates these points. Constitutive splicing of all 5 exons produces the normal hormone but aberrant skipping of exon 3 can lead to the production of a dominant negative isoform and associated Isolated Growth Hormone Deficiency type II (IGHD II). This thesis describes research into understanding the causes of exon 3 skipping and shows that siRNAs targeting the unique exon 2-exon 4 sequence in mutant transcripts can prevent onset of IGHD II in a mouse model. Advisors/Committee Members: John A. Phillips III (committee member), Ronald B. Emeson (committee member), Katherine L. Friedman (committee member), James G. Patton (committee member), Todd R. Graham (Committee Chair).

Subjects/Keywords: Splicing; Exon skipping; Gene therapy  – Methodology; Growth Hormone; RNAi; RNA editing; Somatotropin; Genetic engineering

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Shariat, N. (2008). Growth Hormone Splicing and Treatment of Disease Using RNA Interference. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10630

Chicago Manual of Style (16th Edition):

Shariat, Nikki. “Growth Hormone Splicing and Treatment of Disease Using RNA Interference.” 2008. Doctoral Dissertation, Vanderbilt University. Accessed March 08, 2021. http://hdl.handle.net/1803/10630.

MLA Handbook (7th Edition):

Shariat, Nikki. “Growth Hormone Splicing and Treatment of Disease Using RNA Interference.” 2008. Web. 08 Mar 2021.

Vancouver:

Shariat N. Growth Hormone Splicing and Treatment of Disease Using RNA Interference. [Internet] [Doctoral dissertation]. Vanderbilt University; 2008. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1803/10630.

Council of Science Editors:

Shariat N. Growth Hormone Splicing and Treatment of Disease Using RNA Interference. [Doctoral Dissertation]. Vanderbilt University; 2008. Available from: http://hdl.handle.net/1803/10630


Vanderbilt University

2. Delahanty, Ryan James. Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism.

Degree: PhD, Human Genetics, 2010, Vanderbilt University

TOWARD AN UNDERSTANDING OF THE ROLE OF CHROMOSOME 15Q11-Q13 IN IDIOPATHIC AUTISM RYAN JAMES DELAHANTY Dissertation under the direction of Dr. James S. Sutcliffe The 15q11-q13 region is a genomic interval involved in a growing number of genomic disorders. The genes in the interval are subject to imprinting and parent-of-origin expression effects. Maternal duplication of the 15q11-q13 region is the most frequent chromosomal abnormality associated with autism. Extensive work has indicated that two genes in this interval, UBE3A and GABRB3, show very strong evidence for association with autism. To examine the extent to which these genes may contribute to autism, family-based association studies of UBE3A and GABRB3 were undertaken. Here we have investigated the role of common variants of UBE3A and GABRB3 in autism as well as the an intense investigation of the association of a rare variant, P11S in GABRB3 and its role in autism. In addition, we have investigated MECP2, a gene which when defective causes Rett syndrome, and potentially regulates gene expression of UBE3A and GABRB3. e have used genetic and biochemical methods to investigate two genes in the UBE3A network, ECT2 and GCH1. Finally, we used genotype data and multiplex ligation probe amplification (MLPA) to determine if copy number variation in the form of deletions and duplications in UBE3A and GABRB3 may play a role in the etiology of autism. Our findings indicated that a common allele of MECP2 is associated with autism, which was replicated by another group. We show association with UBE3A and its associated genes ECT2 and GCH1 as well as a relationship between UBE3A and GCH1 gene and protein expression, observed in a model system, and validated in our samples, which may provide guidance and support for a role of UBE3A and its action at the synapse and potential contribution to autism. We show modest association of GABRB3 with autism and epilepsy, but find a single coding variant, P11S, maternally overtransmitted and in such cases dramatically increasing autism risk. Finally, we found little evidence for microdeletions or microduplications in UBE3A and GABRB3 to contribute to autism pathology. The work presented in this thesis expands on earlier findings with regard to the role of GABRB3 and UBE3A in autism and represents an investigation of variants in these and their related genes spanning the spectrum from common variants of modest effect to rare variants of more profound effect. The availability of new technologies to evaluate copy number variation and next generation sequencing will likely uncover a wider role for 15q11-q13 and related loci in autism. The role of more highly penetrant private mutations of this nature is suggested as an avenue for further investigation. Advisors/Committee Members: Lawrence T. Reiter (committee member), John A. Phillips III (committee member), Chun Li (committee member), James Sutcliffe (committee member), Scott Williams (Committee Chair).

Subjects/Keywords: 15q11-q13; association; autism; GABRB3; UBE3A; ECT2; GCH1; CNV; MECP2

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Delahanty, R. J. (2010). Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10492

Chicago Manual of Style (16th Edition):

Delahanty, Ryan James. “Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed March 08, 2021. http://hdl.handle.net/1803/10492.

MLA Handbook (7th Edition):

Delahanty, Ryan James. “Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism.” 2010. Web. 08 Mar 2021.

Vancouver:

Delahanty RJ. Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1803/10492.

Council of Science Editors:

Delahanty RJ. Towards an understanding of the role of chromosome 15q11-q13 in idiopathic autism. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://hdl.handle.net/1803/10492

.