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You searched for +publisher:"Vanderbilt University" +contributor:("James Sutcliffe"). Showing records 1 – 3 of 3 total matches.

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Vanderbilt University

1. Campbell, Nicholas George. Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism.

Degree: PhD, Neuroscience, 2014, Vanderbilt University

Autism spectrum disorder (ASD) is a neuropsychiatric condition with a range of deficits in social reciprocity and communication, and patterns of rigid-compulsive behaviors. ASD prevalence is estimated at approximately 1 in 100 individuals, with substantial evidence for a largely genetic etiology of complex architecture. The work described here is based on the principle that genes involved in the etiology of ASD will converge onto shared biological systems, and those systems will inform investigation into the pathogenesis of ASD. The purpose of this work was to test the hypothesis that genes encoding monoamine regulation networks harbor genetic variants associated with ASD. In part this was driven by the phenomenon of “hyperserotonemia” in a third of ASD cases. Genes in monoamine networks were thus analyzed for presence of ASD associated variation, and downstream functional studies of two such proteins, the adenosine A3 receptor (a regulator of the serotonin transporter) as well as the dopamine transporter, were revealed novel abnormalities. In conclusion, the results are highly supportive that both a genetic and functional liability exists within the broad context of monoamine dysfunction and ASD. Advisors/Committee Members: Randy Blakely (committee member), James Sutcliffe (committee member), Thomas Morgan (committee member), Karoly Mirnics (Committee Chair).

Subjects/Keywords: serotonin; dopamine; genetics; neuroscience; autism

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

APA (6th Edition):

Campbell, N. G. (2014). Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12167

Chicago Manual of Style (16th Edition):

Campbell, Nicholas George. “Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed March 06, 2021. http://hdl.handle.net/1803/12167.

MLA Handbook (7th Edition):

Campbell, Nicholas George. “Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism.” 2014. Web. 06 Mar 2021.

Vancouver:

Campbell NG. Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1803/12167.

Council of Science Editors:

Campbell NG. Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/12167


Vanderbilt University

2. Gorrindo, Phillip. Translational investigations of gastrointestinal comorbidities in children with autism.

Degree: PhD, Neuroscience, 2011, Vanderbilt University

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders. Although research on ASDs has implicated multiple genes in pathogenesis, etiology for the majority of cases remains unknown. In the context of profound etiological and phenotypic complexity, one strategy to seek insight into risk and pathogenesis is to stratify a heterogeneous population based on a prominent feature, resulting in increased homogeneity within population strata. One such feature is gastrointestinal dysfunction (GID), which is present in a subpopulation of individuals with ASDs. A previous report demonstrated signal enrichment for an ASD risk variant in the MET gene specifically in individuals with co-occurring ASD and GID (ASD-GID), suggesting shared genetic risk for both the nervous and gastrointestinal systems due to pleiotropic expression of MET. The objectives of the current studies were to examine relationships between proposed causes of GID and GID outcomes in ASD; to investigate clinical and biological features specific to ASD-GID; and to study the biological roles played by Met in the gastrointestinal system of conditional knockout mice. Children with ASDs, with and without GID, as well as children with GID only, donated a blood sample and were assessed for language and social function, dietary habits and GID status. Met conditional null mice, lacking Met signaling capacity in the GI epithelium, were assessed for repair ability in response to acute epithelial injury. In children with ASDs, no association was found between dietary habits or medication status, and GID outcome. A significant fraction of children with ASD-GID had no expressive language, and had greater social impairment, compared to children with ASD only or GID only. Prevalence of the MET risk variant was increased in the ASD groups. The possibility that children with ASD-GID are more severely impacted is supported by data demonstrating significant elevation of a marker of oxidative stress specifically in this group. In the animal model studies, Met conditional null mice demonstrated impaired healing capacity in response to GI injury. These findings have important implications both for improving clinical care of children with ASDs and co-occurring GID, and for further understanding risk and pathogenesis in a subpopulation of individuals with ASDs. Advisors/Committee Members: James Sutcliffe (committee member), Nancy Brown (committee member), Pat Levitt (committee member), Karoly Mirnics (Committee Chair).

Subjects/Keywords: autism; genetics; gastrointestinal; autism spectrum disorder

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

APA (6th Edition):

Gorrindo, P. (2011). Translational investigations of gastrointestinal comorbidities in children with autism. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14811

Chicago Manual of Style (16th Edition):

Gorrindo, Phillip. “Translational investigations of gastrointestinal comorbidities in children with autism.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed March 06, 2021. http://hdl.handle.net/1803/14811.

MLA Handbook (7th Edition):

Gorrindo, Phillip. “Translational investigations of gastrointestinal comorbidities in children with autism.” 2011. Web. 06 Mar 2021.

Vancouver:

Gorrindo P. Translational investigations of gastrointestinal comorbidities in children with autism. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1803/14811.

Council of Science Editors:

Gorrindo P. Translational investigations of gastrointestinal comorbidities in children with autism. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/14811


Vanderbilt University

3. 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

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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 06, 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. 06 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 06]. 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

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