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 subject:(GCH1). 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. 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


University of Notre Dame

2. Edwin Siu. The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>.

Degree: Biological Sciences, 2011, University of Notre Dame

Mass drug administration, a key malaria control strategy, has been thwarted by the development of drug resistance to nearly all classes of antimalarials in use. Antifolate drugs are antimalarial compounds that target and inhibit the folate pathway necessary for pyrimidine synthesis in the blood stage parasite. Discovering and understanding the evolution of resistance is essential to developing novel treatment regimes and avoiding future treatment failure. Previous studies of P. falciparum malaria parasites derived from the field isolates suggest an association between gch1 copy number variations (CNVs) and resistance to the antimalarial drug pyrimethamine (PYR). However, the actual functional role of this CNV on drug sensitivity and parasite fitness has not been determined. Using the parents and progeny of the genetic cross between clonal parent lines, HB3 and Dd2, we identified a positive correlation between gch1 copy number (CN) and PYR IC50 values and confirmed the phenotypic effect of the gch1 CNV by amplifying the CN in HB3 parasites (a two-fold increase) using the piggyBac transfection system. Our data raise the interesting possibility that the genetic background of resistant parasites, specifically dihydrofolate reductase (DHFR) mutation background, influences the magnitude of effect of gch1 CNV on parasite drug response. Previously, CNVs have been associated with resistance levels in natural parasite populations, however evidence for their direct impact on drug-related traits was lacking. A key outcome of this project was the development of approaches for the continued study of the gch1 CN phenotype. New transfected parasites are already being produced to further explore the role of dhfr background mutations. We have also developed a multiple-reaction monitoring mass- spectroscopy assay to measure changes in flux of the folate biosynthesis pathway caused by the gch1 amplification. This method will enable experiments to determine the mechanism by which gch1 amplification we leads to shifts in drug susceptibility. Advisors/Committee Members: Amanda Hummon, Committee Member, Michael Ferdig, Committee Chair, Jeanne Romero-Severson, Committee Member.

Subjects/Keywords: DHFR; gch1; copy number variation; malaria; Plasmodium falciparum; pfdhfr; GTP-CH; drug resistance; CNV; drug susceptibility; antifolate; pyrimethamine; Plasmodium

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Siu, E. (2011). The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/mp48sb41k33

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Siu, Edwin. “The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>.” 2011. Thesis, University of Notre Dame. Accessed March 08, 2021. https://curate.nd.edu/show/mp48sb41k33.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Siu, Edwin. “The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>.” 2011. Web. 08 Mar 2021.

Vancouver:

Siu E. The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>. [Internet] [Thesis]. University of Notre Dame; 2011. [cited 2021 Mar 08]. Available from: https://curate.nd.edu/show/mp48sb41k33.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Siu E. The Impact of Gene Copy Number on Plasmodium falciparum Antifolate Drug Susceptibility</h1>. [Thesis]. University of Notre Dame; 2011. Available from: https://curate.nd.edu/show/mp48sb41k33

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.