Abstract
Background15q11–13 region is one of the most complex chromosomal regions in the human genome. UBE3A is an important candidate gene of autism spectrum disorder (ASD), which located at the 15q11–13 region and encodes ubiquitin-protein ligase E3A. Previous studies about UBE3A gene and ASD have shown inconsistent results and few studies were performed in Chinese population. This study aimed to detect the genetic mutations of UBE3A gene in Chinese Han population with ASD and analyze genetic association between these variants and ASD.MethodsThe samples consisted of 192 patients with autism according to the DSM-IV diagnostic criteria and 192 healthy controls. We searched for mutations at coding sequence (CDS) regions and their adjacent non-coding regions of UBE3A gene using the high resolution melting (HRM) and Sanger sequencing methods. We further increased sample size to validate the detected variants using HRM and conducted association analysis between case and control groups.ResultsA known single nucleotide polymorphism (T > C, rs150331504) located at the CDS4 and a known 5 bp insertion/deletion variation (AACTC+/−, rs71127053) located at the intron region of the upstream 288 bp of the CDS2 of UBE3A gene were detected using Sanger sequencing method. The ASD samples of case group were 391 for rs71127053, 384 for rs150331504 and 384 healthy controls, which were used to make an association analysis. The results of association analysis suggested that there were no significant difference about the allele and genotype frequencies of rs71127053 and rs150331504 between case and control groups after extending the sample size. Besides, rs150331504 is a synonymous mutation and we compared the secondary structure and minimum free energy (MFE) of mRNA harboring the allele T or C of rs150331504 using RNAfold software. We found that the centroid secondary structure apparently differs along with the polymorphisms of rs150331504 T > C, the results suggested that this variant might change the secondary structure of mRNA of UBE3A gene. We did not detect mutations in other coding regions of UBE3A gene.ConclusionsThese findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.
Highlights
Autism is a childhood-onset neurodevelopmental disorder characterized by impaired social interactions and communication, restricted interests and repetitive behaviors, the onset of autism is usually before 3 years old
We found that the centroid secondary structure apparently differs along with the polymorphisms of rs150331504 T > C, the results suggested that this variant might change the secondary structure of mRNA of UBE3A gene and influence its biological functions
In this study, we investigated the role of UBE3A gene in autism spectrum disorder (ASD) by comprehensive screening for coding sequence regions and their adjacent non-coding regions of UBE3A gen for mutations
Summary
Autism is a childhood-onset neurodevelopmental disorder characterized by impaired social interactions and communication, restricted interests and repetitive behaviors, the onset of autism is usually before 3 years old. Manual of Mental Disorders (DSM-5) removed delayed language development from the list of diagnose criteria, autism covered a host of diseases such as Asperger’s disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified and redefined itself as autism spectrum disorder (ASD) [1]. Along with changes in diagnosis criteria and improved understanding and awareness about this disease, the prevalence of ASD increased in the past decade according to the report of Centers for Disease Control and. The estimated prevalence of ASD in Chinese population ranged from 2.8 to 29.5 per 10, 000 persons according to a review that summarized the findings in Chinese population from several areas [4]. Multiple twin and family studies have confirmed that genetic factors play an important role in the development of ASD and the heritability is about 90% [7]. Recent genetic studies have found that hundreds of genetic variants, including common and rare variants, contributing to the occurrence of ASD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
