DRD2Gene Mutation Detection In Autism And Schizophrenia

Autism is a disorder of neural development characterized by impaired socialinteraction, verbal and non-verbal communication, restricted, repetitive or stereotypedbehavior. The diagnosis require that symptoms become apparent before a child is threeyears old.The prevalence of autism is about0.6%worldwide and is on the rise in recent years.Multiple factors are involved in the etiology of autism such as genetic, perinatal riskfactors, organic brain diseases, and neurological abnormalities. However, it is generallybelieved to be the result of interaction between genetic and environmental factors. Geneticfactors are the main factor in the etiology of autism, and autism is a polygenic disease. Sofar, a lot of autism susceptibility genes with high penetrance have been found.Schizophrenia is a mental disorder characterized by delusions, hallucination; lack ofemotion and motivation and behavioral abnormalities. The lifetime prevalence ofschizophrenia is about1%. Family survey, adoption and twin studies have all shown thatheredity is an important factor in causing the disease, and the heritability of SZ is about80%. Some candidate genes and many chromosomal regions have been found by linkageand association analysis. SZ is the fourth leading cause of disability in the world. Clinicalmanifestations of child and adolescent schizophrenia are more serious, and poor inprognosis.DRD2has been considerd as a susceptibility gene for autism and schizophrenia,DRD2, located on human chromosome11q23.1, contains9exons,a number of introns andshort tandem repeat (STR). DRD2,as a dopamine receptor subtypes, belong to the G proteincoupled receptors, it inhibit the activity of adenylate cyclase, reduce the level of the cAMP.The abnormal regulation of DRD2gene could result in the abnormal expression ofdopamine D2receptors, and the dysfunction of dopamine in certain area of the brain couldlead to mental illness.Objective To screen of exonic mutations of DRD2in autism and schizophrenia patientsMethodsStage1: Mutation screening of exon sequence of DRD2gene in autism.A total of38autism patients were recruited from Shandong Mental HealthCenter(2000-2002), and1095nomal controls were taken from the blood donors ofShandong Blood Center. The normal comtrols were divided into two groups (95and1000).The average age of the cases was5.10±1.61.The male to female ratio was18:1(36/2),and there was no blood relationship between the patients. The average age of the95controlswas26.03±6.84, and the male to female ratio was1.02：1(48/47). The average age of the1000controls was23.08±5.67, and the male to female ratio was1.32：1(569/431). A totalof15pairs of primers covering all of the exon sequences of DRD2gene were applied toamplify the3pooled DNA samples (38cases,95controls and1000controls) by PCR. Thenthe PCR product was diluted as template for COLD-PCR amplification.The high resolutionmelting curve analysis (HRM) was carried out to compare the curve difference between thecase group and the control groups respectively.Stage2: Mutation screening of exon sequence of DRD2gene in child and adolescentonset schizophreniaA total of89child and adolescent onset schizophrenia patients were recruited fromShandong Mental Health Center (2005-2008). A total of1095normal controls were takenfrom the Shandong Blood Center donors, and divided into two groups (95,1000). Theaverage age of the cases was16.14±2.77, and the male to female ratio was1:0.98(45/44).There was no blood relationship between the patients. The average age of the95controlswas26.03±6.84, and the male to female ratio was1.02：1(48/47). The average age of the1000controls was23.08±5.67, and the male to female ratio was1.32：1(569/431). A totalof15pairs of primers covering all of the exon sequences of DRD2gene were applied toamplify the3pooled DNA samples (89cases,95controls and1000controls) by PCR, andthen PCR product was diluted as template for COLD-PCR amplification.The HRM wascarried out to compare the curve difference of case group and control groups respectively.ResultsThe data analysis of the three DNA Pooling samples revealed that exons of DRD2gene was not mutated in autism patients in this study.No mutation was revealed in the DRD2gene in the child and adolescent onsetschizophrenia studied.ConclusionNo exonic mutation was found in the DRD2gene in both of the autism and child andadolescent onset schizophrenia patients in this study.