Work

Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals

Year: 2015

Type: article

Abstract: The oxytocin receptor (OXTR) gene has been implicated as a risk gene for autism spectrum disorder (ASD)—a neurodevelopmental disorder with essential features of impairments in social communication and reciprocal interaction. The genetic associations between common variations in OXTR and ASD have been reported in multiple ethnic populations. However, little is known about the distribution of rare variations within OXTR in ASD patients. In this study, we resequenced the full length of OXTR in 105 ASD individuals using an approach that combined the power of next-generation sequencing technology, long-range PCR and DNA pooling. We demonstrated that rare variants with minor allele frequency as low as 0.05% could be reliably detected by our method. We identified 28 novel variants including potential functional variants in the intron region and one rare missense variant (R150S). We subsequently performed Sanger sequencing and validated five novel variants located in previously suggested candidate regions in ASD individuals. Further sequencing of 312 healthy subjects showed that the burden of rare variants is significantly higher in ASDs compared with healthy individuals. Our results support that the rare variation in OXTR gene might be involved in ASD. People harboring rare variants in the receptor gene for the hormone oxytocin may be at higher risk of autism spectrum disorder (ASD). Oxytocin is synthesized in the brain, and recent studies indicate it plays a vital role in social behaviors. For this reason, the dysfunction of the oxytocin receptor gene (OXTR) has been implicated in the development of ASD. Katsushi Tokunaga and Tsukasa Sasaki at the University of Tokyo, with scientists across Japan, have developed a method for pinpointing rare OXTR variants. This highly sensitive method, incorporating next-generation sequencing, enabled the team to uncover 28 novel variants in 105 ASD sufferers. They further examined top candidate regions of OXTR in additional 312 healthy individuals, and found ASD individuals carries a higher burden of rare variants compared with the healthy individuals. Further research with a larger sample size is needed.

Source: Human Genome Variation

DOI: 10.1038/hgv.2015.24