Ramifications of Copy Number Variants in Autism
Open Access
- Author:
- Khoo, Su Jen
- Area of Honors:
- Biotechnology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Maria Krasilnikova, Thesis Supervisor
Scott Brian Selleck, Thesis Supervisor
David Scott Gilmour, Thesis Honors Advisor
Dr. Wendy Hanna-Rose, Faculty Reader - Keywords:
- Autism
copy number variants (CNV)
DNA micro array
de novo
pathogenic
duplications
deletions - Abstract:
- Autism has emerged as an important childhood concern regarding one’s social and cognitive developmental condition. To date, many uncertainties manifest when questions are raised regarding one single explanation behind this developmental impairment. Various resources have emphasized the roles of environment [10, 83], epigenetics [83] and genetics [3, 4, 6] in determining the potential risk for autism. Symptoms and degree of penetrance of autism varies in every child that is observed in terms of social communication impairments [89], repetitive behavioral patterns [19] and restrained interests [19, 89]. Recent interest in this area of research has inspired collaboration between the Biochemistry and Molecular Biology Department in Pennsylvania State University, Department of Genome Sciences from University of Washington and the Medical Investigation of Neurodevelopmental Disorders (MIND) team from University California Davis. The collaborative work has incorporated a combination of technological advances that include detection of copy number variants (CNVs), implementing high density customized oligonucleotide arrays and clinical assessments to elicit better understanding regarding factors that can lead to autism. The study is comprised of conducting microarray scans on 554 blood DNA samples provided by the MIND Institute, in which 274 samples were obtained from autistic individuals while another 280 originated from normally developing individuals. Results obtained from the microarray analysis enabled investigators to compare the structural variants of individuals and detect dysregulation of genes in respective chromosomal regions that could cause neurological disorders [69]. Additional clinical assessments, primarily the Mullen Scales of Learning and Vineland Adaptive Behavior Scales provided the assessment of individuals’ susceptibility to neurolodevelopmental disorders based on overt phenotypes shown in their socialization and living skills [25]. Eleven significant cases of pathogenic deletion and duplication events found in autistic and normally developing individuals were discussed in this dissertation. These events constituted large affected chromosomal areas in the genome and were further analyzed to cause a loss or gain of genes involved in neurodevelopmental pathways that could possibly lead to autism.