| Autism (MIM 209850) is characterized by delayed language development, trouble with social interactions, stereotyped behaviors and interested in a very narrow range of things, which categorize to pervasive developmental disorders. Autism is the most common childhood psychiatric disorders, and its worldwide prevenlance is about 1-6‰.In recent years, researchers has revealed a number of autism susceptibility loci and genes, but the major susceptibility gene is still unclearly. Family-based linkage analysis has revealed several regions associated with autism, of which the chromosome 7q, also known as AUST1, is the most replicated autism susceptibility locus and was also confirmed by meta-analysis. Some genes within this region, such as RELN, MET, FOXP2, CNTNAP2 and EN2 genes has been evident to be candidate genes of autism by association-study, though results of previously study is contradictory. In this study, we are intent to clarify which are the most importance autism susceptibility genes located in the chromosome 7q.In total of 455 Chinese Han patients with autism was employed in this study, all of which were diagnosed according to DSM-IV and signed informed consent. And we also recruited 1097 Chinese Han people as control. Illumina Human CNV-370 microarray was used to genotype all the candidate genes and case-control association study was performed. There are 3 regions in chromosome 7q gained highest repeatability by linkage analysis:7q22,7q31, and 7q35-qter; So we selected 10 candidate genes (NPTX2,LRRN3,GPR85,FOXP2,MET,ST7,WNT2,GRM8,EN2 and CNPY1gene) in the above regions for analysis.Our results indicated that 4 genes were significantly associated with autism, which are the MET gene (rs2237712,χ2=5.845, p=0.0156; rs2237713,χ2=6.1, p=0.0135), ST7 gene (rs7788320,χ2=5.037, p=0.0248; rs7785492,χ2=4.341, p=0.0372), EN2 gene (rs1861958, x2=4.341, p =0.0372) and GRM8 gene (rs2108849,χ2=4.92, p=0.0266; rs1419472, =4.12, p=0.0424; rs11563410,χ2=6.573, p=0.0104; rs1156653,χ2= p=0.0409; rs2283089,χ2=4.377, p=0.0364). In addition, previous studies in our lab has confirmed that CNTNAP2 gene,which located in 7q35-36 are also significantly associated with Chinese Han autistic children. In summary, MET, ST7, GRM8, EN2 and CNTNAP2 gene may be the important autism susceptibility genes which located on chromosome 7q. Schizophrenia (MIM 181500) is one of the most common mental illnesses. It is a severe psychiatric disorder characterized by loss of contact with reality (psychosis), hallucinations, delusions, distorted thinking, strange feelings, diminished motivation and various cognitive impairments that disturbed work and social functioning. Worldwidely, about 1%of the population is affected by schizophrenia. It is a complex, multifactorial disorder that occuring involved of multiple genes and environmental factors. Several schizophrenia susceptibility locus have been mapped to 1p, 1q,4p,6p,7q,8p,13q,22q and many other chromosomal regions, and it is supposed that many genes predisposing to schizophrenia.Human RELN (Reelin) gene located on chromosome 7q22, which encodes a 3461Aa secreted glycoprotein that is essential for neuronal ventrcular migration to form a highly laminated structures in the cerebral cortex, hippocampus and cerebellum during the embryonic CNS development, and it also play important roles in regulating synaptic plasticity throughout the adult CNS. In post-mortem study of schizophrenia, bipolar, autism and lissencephaly individuals showed a significantly decrease of RELN expression in the brain. Researchers raiesd the hypothesis that maybe RELN gene is involved in the pathogenesis of a variety of psychiatric disorders, such as schizophrenia, depression, bipolar disorders and autism. Previously association study indicated that RELN gene maybe one of the susceptibility genes of schizophrenia, but there is no evidences for the correlation of RELN gene and the Chinese Schizophrenia patients.In total of 44 Han Chinese Schizophrenia families was employed in this study, including 244 family members, of which 104 were diagnosed to be schizophrenia according to DSM-IV criteria. There are 2 SNPs within the RELN gene, rs2229864 and rs736707, was genotyping by TaqMan-PCR method and then analyzed by transmission disequilibrium test (TDT). Accroding to our results, the frequency of SNP-rs2229864 C-allele were significantly different between the schizophrenia pedigrees and normal control (x2=7.049, p=0.0079), so did the "TT" haplotype of rs2229864-rs736707 (x2=7.438, p=0.0064). This study shows that RELN gene maybe associated with schizophrenia in Chinese Han population and it is possible to be a schizophrenia susceptibility gene. |
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