Genome-wide microarray analysis in a case-control study reveals elevated level of global copy number burden in autism
Open Access
- Author:
- Yeoh, Kian Hui
- 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
cnv
copy number burden
ASD
microarray
genome
aCGH
array comparative genomic hybridization - Abstract:
- Copy number variations (CNV), or structural genomic variations, have recently been shown to be implicated in and associated with numerous human neurodevelopmental disorders such as autism spectrum disorders (ASD), schizophrenia, epilepsy, mental retardations, developmental delays, bipolar disorder, intellectual disability (ID) and many other human diseases. In this study, we used a custom-design DNA microarray targeted at regions flanked by segmental duplications (SD) to evaluate and compare global copy number burden between 274 autistic (AU) patients and 280 typically developing (TD) individuals from the general population. We found that there was an elevated level of global CNV burden in AU individuals (Mann-Whitney Test, U= 23449, p= 0.00185). Additionally, we showed that total average duplication length in AU individuals was also significantly higher than that of controls (Mann-Whitney Test, U= 28129, p= 0.0109) compared to total average deletion length (Mann-Whitney Test, U= 20804, p=0.432). Interestingly, this differential level of global burden between cases and controls was mostly detected in the genomic backbone or non-hotspot region (Mann-Whitney Test, U=7992, p=0.0128), but not the genomic hotspot regions (Mann-Whitney Test, U=28987, p=0.513) as we originally expected. The data from this case-control study demonstrated an elevated level of copy number changes in autistic individuals, which was primarily represented by large duplication events located in the non-hotspot or genomic backbone regions. The findings from this study also implicated that there may be an alternative mechanism other than non-allelic homologous recombination (NAHR) involved in this significant copy number variation in autism.