2013 Fiscal Year Annual Research Report

The genetic and functional study of the rare variants within oxytocin receptore (OXTR) gene in autism spectrum disorder patients and healthy individuals.

Research Project

Project/Area Number	25893290
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	LIU XIAOXI 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (20709216)
Project Period (FY)	2013-08-30 – 2015-03-31
Keywords	Autism spectrum disorder / Oxytocin receptor / OXTR / ASD
Research Abstract	Recent studies on oxytocin (OT) demonstrate that beyond its well-documented functions in labor induction and milk ejection, this nine-amino-acid peptide plays a critical role in regulating a wide range of social behaviors including pair bonding, maternal parenting and social memory). In human genetic studies, common variants especially the ones in the third intron of OXTR have been reported to be associated with ASD. However besides the common variants, rare variants have been not explored yet. To understand the comprehensive genetic landscape of OXTR especially in relationship to ASD. The targeted re-sequencing of OXTR) was carried out in 105 Japanese autism spectrum disorder (ASD) individuals. First Long range PCR were performed to amplify the whole region of OXTR gene. The PCR products of all patients were quantitated and merged into four pools at equal molar amount. Then Next generation sequencing was followed. Finally a total 125 mutations were identified and 26 were regard as novel mutations since they were not registered in 1000 genome project and other public database. Of particular interest, two novel non-synonymous SNPs were identified and confirmed in ASD patients. Bioinformatics analysis suggest these two mutant may have a highly deleterious role and may affect the receptor activation. And these two mutations were not found in another 384 healthy individuals. In conclusion this project reported a number of novel mutations of OXTR in ASD patients. This finding expands our understanding of the contribution of rare variants of OXTR to ASD.
Current Status of Research Progress	Reason 翌年度、交付申請を辞退するため、記入しない。
Strategy for Future Research Activity	翌年度、交付申請を辞退するため、記入しない。