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Analysis of reelin as a candidate gene for autism

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 relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.

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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 thank John Broxholme for help in bioinformatic analysis, Pat Scudder and Tatjana Kraus for technical support, Elena Maestrini, Gabrielle Barnby, Elena Bacchelli, Yvonne Jones and Robert Esnouf for helpful discussions and critical comments on the manuscript. The DNA samples of German control individuals were collected by Laura Diedrichs. This study is funded in part by support from the UK Medical Research Council, The Wellcome Trust, BIOMED 2 (CT-97-2759), EC Fifth Framework (QLG2-CT-1999-0094), Telethon—Italy (E.1007), the Janus Korczak Foundation, Deutsche Forschungsgemeinschaft, Foundation France Télécom, Conseil Régional Midi-Pyrénées, Danish Medical Research Council, Sofiefonden, the Beatrice Surovell Haskells Fund for Child Mental Health Research of Copenhagen, the Danish Natural Science Research Council (9802210), the National Institute of Child Health and Development (5-P01-HD-35482-02) and the National Institutes of Health (MO1 RR06022 GCRC NIH, NIH K05 MH01196, K02 MH01389). EB is funded by a University of Oxford Graduate Prize Studentship and 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/

Primer 3 Program, http://www.genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi

BLAST search, http://www.ncbi.nlm.nih.gov/BLAST

PromoterInspector Program, http://gsf.de/biodv

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Correspondence to A J Bailey or A P Monaco.

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Bonora, E., Beyer, K., Lamb, J. et al. Analysis of reelin as a candidate gene for autism. Mol Psychiatry 8, 885–892 (2003). https://doi.org/10.1038/sj.mp.4001310

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Keywords

  • autism
  • candidate genes
  • brain development
  • reelin
  • mutation screening

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