Mutation screening of the UBE3A gene in Chinese Han population with autism
Abstract Background 15q11-13 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 variation of UBE3A gene in Chinese Han population with ASD and analyze the genetic association between these variations and ASD. Methods The samples consisted of 192 patients with clinical diagnosis of 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 analyzed the difference of allele and genotype frequencies between case and control groups. Results A 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 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 analyzed the minimum free energy (MFE) of mRNA coded by the different alleles of rs150331504. The result showed that MFE values of the allele T and allele C of rs150331504 were different and indicated that the variant might alter the mRNA secondary structure. We did not detect mutations in other coding regions of UBE3A gene. Conclusions These findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.