The Correlation between Gene Expression and DNA Methylation Levels of RAS p21 Protein Activator 3 (RASA3) Gene in Saudi Autistic Children
Aisha Alrofaidi
*
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Rawan Saeed Alghamdi
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Mona Alharbi
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Khloud Algothmi
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Reem Farsi
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Najla Alburae
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Magdah Ganash
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Fatemah Basingab
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Sheren Azhari
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Heba Alkhatabi
King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia.
Aisha Elaimi
King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia.
Manal Shaabad
King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia.
Ashraf Dallol
King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia.
Amany Alqosaibi
Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Mohammed Jan
King Abdulaziz University, College of Medicine, Jeddah, Saudi Arabia.
Hesham Aldhalaan
Center for Autism Research at King Faisal Specialist Hospital and Research Center (KFSH&RC), Saudi Arabia.
Safiah Alhazmi
Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
*Author to whom correspondence should be addressed.
Abstract
The potential role of DNA methylation pattern in autism has been provided by revealing the differences in methylation level of multiple genes which are significantly associated with their expression and implicated in ASD pathogenesis. RASA3 is a member of GTPase-activating proteins, RASA3 is highly expressed in brain tissues and can be deregulated by different epigenetic mechanisms. Many studies reported that differentially expressed RASA3 is correlated with its aberrant methylation. Accordingly, this has been suggested that deferentially expression of RASA3 may be correlated with its methylation levels which could play a role in ASD which brought our attention to identify differentially-expressed genes that could be associated with their methylation level of ASD in Saudi population, by performing comparative gene expression of RASA3 then investigate its relation to methylation level.
This study was conducted on 18 Saudi autistic children as well as their healthy-control siblings. Relative expression of a candidate gene (RASA3) was measured using RT-qPCR. Furthermore, MethyLight assay was performed to estimate methylation level and evaluate its impact on RASA3 expression. Interestingly, RASA3 expression has found to be dysregulated in ASD cases. In contrast, MethyLight assay result showed no differences in the methylation patterns among ASD cases in the candidate region. However, it remains an open question whether these dysregulations of RASA3 expression could be a biomarker for early screening/detection of some cases which may also suggest a role for RasGAPs in autistic brain function.
Keywords: DNA methylation, Autism, ASD, RASA3