A Study Of SYNGAP1 Gene And UPF3B Gene With Mental Retardation In Qinba Mountain Area

Mental retardation (retardation, MR), effected by certain genetic factors, is a human mental disorder. Qinba mountain region located at the interspace of Shaanxi, Sichuan, Gansu and Hubei province, is one of the main impoverished regions of China and is also a high-risk area for the mental retardation disease. So, revealing the genectic causes of local mental retardation disease is significant from practical and theoretical points of role. In present study, the SYNGAP1 gene and UPF3B gene were selected as candidate genes, and the 13 SNPS sites were selected as genetic markers, to study the relationship between polymorphism of the above genes and MR risk in the Chinese Han population of Qinba mountain region.SYNGAP1 gene encoding protein is a special GTP active protein expressed in brain. It acts by inhibiting the activity of Ras protein, which therefore controls its downstream signaling pathways. SYNGAP1 gene encoding protein also participates in the process of neural synaptic plasticity as an important member of protein complex for the NMDA receptors. UPF3B genetic encoding protein participates in outer nuclear transport process of mRNA and nonsense codon mediated mRNA degradation (NMD) process. In view of the important function of the SYNGAP1 gene and UPF3B gene to human, it is hypothesized that the polymorphism of the two genes may correlate with MR susceptibility of Chinese Han population of Qinba mountain region. A study based on the nuclear pedigree for 456 samples from Chinese Han population of Qinba mountain region was performed, using thirteen SNPs sites in the two genes, with the aim to investigate the relationship between their polymorphism and MR susceptibility.The PCR-SSCP, PCR-RFLP and sequencing methods were used in the genotyping of the markers. Later, the nuclear pedigree datas were treated with Microsoft Excel 2007. The Hardy-Weinberg equilibrium (HWE), linkage disequilibrium (LD) block structure and TDT analysis were performed by Haploview 4.1. The HRR and HHRR analysis were performed by UNPHASE 3.13, and statistical power analysis was performed using the G*Power 2.0 program.In the study of SYNGAP1 genes, the results show that the eight markers are all in HWE balance; Linkage disequilibrium (LD) analysis revealed that the rs75045763-rs453590 and rs411136-rs12204193-rs2247385 were in strong LD, separately; The TDT analysis show that the marker rs10807124 was over-transmission from parents to MR offspring (P= 0.0071);HRR analysis and HHRR analysis of rs10807124 also shows positive results (PHRR=0.0067, PHHRR=0.0148); The other seven markers on SYNGAP1 gene are shows negativeresults in HHRR, TDT and HRR analysis (P>0.05);haplotype analysis shows that the polymorphism of the two blocks are not association with the MR in Qinba mountains.In the study of UPF3B genes, the results show that the five markers are all in HWE balance; Linkage disequilibrium (LD) analysis revealed that the rs2496207-rs2285552 were in strong LD; The result shows that all five markers polymorphism are not association with the MR in Qinba mountains in TDT analysis, HRR analysis, HHRR analysis and haplotype analysis (P>0.05).The resultes indicate SYNGAP1 gene polymorphism closely correlated with MR risk in Chinese Han population of Qinba mountain region, it was supposed that mutation on this gene lead to MR disease in Qinba mountain region; UPF3B gene polymorphism showed negative correlation with MR desease in Chinese Han population of Qinba mountain region, and mutation on this gene is not a major genetic reason for MR desease. And detail studies are still needed in future.