Whole Genome CNV Analysis Of Autism And Study On A Case With 15q11.2-q13 Microduplication

Background Autism is a severe childhood neurodevelopmental disorder characterized by impairment of social and communication skills, repetitive and stereotypical behaviors,restricted range of interests and an onset before 3 years of age.Males are affected by autism approximately 4 times more frequently than females.Prevalence estimate of this disease is about 0.3‰～1‰.Autism is a complex disease with high heritability.Cytogenetics study showed that it has a high incidence of chromosome abnormality.Many related loci have been identified by large samples,twin pairs and trios study.Also,several genes are suspected to participate in the process of disease occurring.However,the etiology of autism is still unknown.The study in the last two years shows that CNVs might be related to autism.Objective Investigate the copy number variations(CNVs) in Chinese Han autism patients and identify possible susceptibility locus.Methods 32 autism cases of Chinese Han population were genotyped by Human CNV370-Duo beadarray.Results were analyzed using beadstudio software to identify CNVs.The karyotype of one subject with large repeated region was analyzed by G-binding and N-binding technology.Based on the target gene,BAC clone was selected from BAC library and validated the microduplication by FISH.Results The date of genotyping were analysed by BeadStudio 3.3.7 software.The call rates of all samples are above 99.0%,most of which are 99.8%.Whole genome CNVs was analysed by cnv Partition v 1.2.1. software.227 CNVs were discovered,of which a 8Mb microduplication in the region 15q11.2-q13 was found in a autism patient.Karyotype of the patient was identified as 47,XY,+mar by G-banding,N-banding,and the additional minichromosome was confirmed to be the replication of the region 15q11.2-q13 by FISH.Conclusions 1.227 CNVs were found in 32 autism patients by CNVs analysis,of which one,a microreplication in 15q11.2-q13,may be associated with autism,and the other 226 are polymorphisms.2. Karyotype was identified as 47,XY,+mar by G-banding,N-banding in the patient harbor the potent autism-associated CNV.The results of FISH showed that the additional chromatin is the replication of the region 15q11.2-q13.