ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population

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dc.contributor.advisorO'Ryan, Colleenen_ZA
dc.contributor.advisorRoden, Lauraen_ZA
dc.contributor.authorDe Waal, Margarethaen_ZA
dc.date.accessioned2017-01-23T07:46:04Z
dc.date.available2017-01-23T07:46:04Z
dc.date.issued2016en_ZA
dc.description.abstractAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by behavioural and social impairments. ASD shows evidence of a genetic aetiology, with a large body of research linking ASD to polymorphisms in several different genes and gene families, including those involved in circadian rhythm generation and melatonin biosynthesis. Sleep disorders are highly comorbid with ASD in both children and adults, and range from sleep onset delay, phase shift and sleep disruption. These parasomnias can have a significant impact on the quality of life for persons with ASD and their families, and sleep deprivation can feed into the behavioural deficits in ASD. Melatonin supplementation is often prescribed to assist in alleviating the above mentioned sleep dysfunction. Melatonin is a hormone in the circadian clock system, and is a biochemical signal for darkness to synchronise peripheral cells to the master oscillator. Clinical trials reported that melatonin supplementation at night assists in sleep initiation. However both the mode of action of supplemental melatonin, as well as whether melatonin deficiency is common in ASD, remains unclear. Furthermore, any research on ASD is often hamstrung by the heterogeneous nature of the disorder, necessitating clear phenotyping. This study examines single nucleotide polymorphisms (SNPs) in the gene acetylserotonin methyl transferase (ASMT), which encodes an enzyme in melatonin biosynthesis, in a South African ASD cohort (n=28) and controls (n=6). All participants completed and Autism Diagnostic Observation Schedule-2 assessment that allowed partitioning of the ASD individuals into ASD endophenotypes, to reduce phenotyping heterogeneity. This study found SNPs previously associated with ASD in the promoter and intronic region. Additionally, this study found novel SNPs, and a SNP in a putative transcription factor binding site not previously associated with ASD. The associations found between SNPs and ASD endophenotypes, together with the positions of the SNPs, suggest a potential link between ASMT polymorphisms and ASD symptom severity. Further research, using language assessment tools as well as quantitative measures of melatonin and sleep disruption, may establish the role of melatonin in language impairment in ASD.en_ZA
dc.identifier.apacitationDe Waal, M. (2016). <i>ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology. Retrieved from http://hdl.handle.net/11427/22888en_ZA
dc.identifier.chicagocitationDe Waal, Margaretha. <i>"ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology, 2016. http://hdl.handle.net/11427/22888en_ZA
dc.identifier.citationDe Waal, M. 2016. ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - De Waal, Margaretha AB - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by behavioural and social impairments. ASD shows evidence of a genetic aetiology, with a large body of research linking ASD to polymorphisms in several different genes and gene families, including those involved in circadian rhythm generation and melatonin biosynthesis. Sleep disorders are highly comorbid with ASD in both children and adults, and range from sleep onset delay, phase shift and sleep disruption. These parasomnias can have a significant impact on the quality of life for persons with ASD and their families, and sleep deprivation can feed into the behavioural deficits in ASD. Melatonin supplementation is often prescribed to assist in alleviating the above mentioned sleep dysfunction. Melatonin is a hormone in the circadian clock system, and is a biochemical signal for darkness to synchronise peripheral cells to the master oscillator. Clinical trials reported that melatonin supplementation at night assists in sleep initiation. However both the mode of action of supplemental melatonin, as well as whether melatonin deficiency is common in ASD, remains unclear. Furthermore, any research on ASD is often hamstrung by the heterogeneous nature of the disorder, necessitating clear phenotyping. This study examines single nucleotide polymorphisms (SNPs) in the gene acetylserotonin methyl transferase (ASMT), which encodes an enzyme in melatonin biosynthesis, in a South African ASD cohort (n=28) and controls (n=6). All participants completed and Autism Diagnostic Observation Schedule-2 assessment that allowed partitioning of the ASD individuals into ASD endophenotypes, to reduce phenotyping heterogeneity. This study found SNPs previously associated with ASD in the promoter and intronic region. Additionally, this study found novel SNPs, and a SNP in a putative transcription factor binding site not previously associated with ASD. The associations found between SNPs and ASD endophenotypes, together with the positions of the SNPs, suggest a potential link between ASMT polymorphisms and ASD symptom severity. Further research, using language assessment tools as well as quantitative measures of melatonin and sleep disruption, may establish the role of melatonin in language impairment in ASD. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population TI - ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population UR - http://hdl.handle.net/11427/22888 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22888
dc.identifier.vancouvercitationDe Waal M. ASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African population. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/22888en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMolecular and Cell Biologyen_ZA
dc.titleASMT gene polymorphisms are associated with Autism Spectrum Disorder (ASD) symptom severity in a South African populationen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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