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Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene

Molecular Psychiatry volume 8, pages 916–924 (2003)Cite this article

Abstract

The results from several genome scans indicate that chromosome 2q21–q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.

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Acknowledgements

We thank all the families who have participated in the study and the professionals who continue to make this study possible. We would like to thank Professor Pasquale Chieco and Professor Vilma Mantovani at the Center for Applied Biomedical Research (CRBA), St Orsola University Hospital, Bologna, for access to DHPLC technology. This study is funded in part by support from Telethon-Italy (E.1007), the National Alliance for Autism Research, Fondazione Cassa di Risparmio in Bologna, Deutsche Forschungsgemeinschaft, the UK Medical Research Council, The Wellcome Trust, APM is a Wellcome Trust Principal Research Fellow.

Electronic-database information

International Molecular Genetic Study of Autism Consortium (IMGSAC), http://www.well.ox.ac.uk/~maestrin/iat.html; Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/; UCSC genome browser, http://genome.ucsc.edu/; Primer 3 Program, http://www.genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi; BLAST search, http://www.ncbi.nlm.nih.gov/BLAST; INSIZER program, http://zeon.well.ox.ac.uk/git-bin/insizer; ESE finder, http://exon.cshl.org/ESE/; dbSNP, http://www.ncbi.nlm.nih.gov/SNP/; SPLICEVIEW program, http://www.itba.mi.cnr.it/webgene/.

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Author notes

  1. E Bacchelli and F Blasi: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Dipartimento di Biologia Evoluzionistica Sperimentale, University of Bologna, Bologna, Italy

    E Bacchelli, F Blasi, M Biondolillo & E Maestrini

  2. The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    J A Lamb, E Bonora, G Barnby & A P Monaco

  3. Genetic and Developmental Psychiatry and Department of Child and Adolescent Psychiatry, Centre for Social, Institute of Psychiatry, London, UK

    J Parr & A J Bailey

  4. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    K S Beyer, S M Klauck & A Poustka

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International Molecular Genetic Study of Autism Consortium (IMGSAC)

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Correspondence to E Maestrini.

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Bacchelli, E., Blasi, F., Biondolillo, M. et al. Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene. Mol Psychiatry 8, 916–924 (2003). https://doi.org/10.1038/sj.mp.4001340

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