title: Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region.
abstract: Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify the relevant gene and report the analysis of four adjacent genes localised to a 800 kb region in 7q32 that contains an imprinted domain: PEG1/MEST, COPG2, CPA1 and CPA5-a previously uncharacterised member of the carboxypeptidase gene family. Screening these genes for DNA changes and association analysis using intragenic single nucleotide polymorphisms (SNPs) provided no evidence for an etiological role in IMGSAC families. We also searched for imprinting mutations potentially implicated in autism: analysis of both DNA methylation and replication timing indicated a normal imprinting regulation of the PEG1/COPG2 domain in blood lymphocytes of all patients tested. The analysis of these four genes strongly suggests that they do not play a major role in autism aetiology, and delineates our strategy to screen additional candidate genes in the AUTS1 locus.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: E
authors.initials: E
authors.lastname: Bonora
authors.forename: E
authors.initials: E
authors.lastname: Bacchelli
authors.forename: E R
authors.initials: ER
authors.lastname: Levy
authors.forename: F
authors.initials: F
authors.lastname: Blasi
authors.forename: A
authors.initials: A
authors.lastname: Marlow
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: E
authors.initials: E
authors.lastname: Maestrini
mesh_terms: D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D002268:Carboxypeptidases / Q000235:genetics*; D043422:Carboxypeptidases A; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D020756:Coatomer Protein; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004261:DNA Replication; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C485814:COPG2 protein, human; D020756:Coatomer Protein; D017931:DNA Primers; D011506:Proteins; C103637:mesoderm specific transcript protein; D002268:Carboxypeptidases; C473693:CPA5 protein, human; D043422:Carboxypeptidases A