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Autism spectrum disorders associated with X chromosome markers in French-Canadian males

Molecular Psychiatry volume 11, pages 206–213 (2006)Cite this article

Abstract

It is now well established that genetic factors play an important role in the pathogenesis of autism disorder and converging lines of evidence suggest the implication of the X chromosome. Using a sample of subjects diagnosed with autism spectrum disorders, exclusively composed of males from French-Canadian (FC) origin, we tested markers covering the entire X chromosome using a family-based association study. Our initial analysis revealed the presence of association at two loci: DXS6789 (P=0.026) and DXS8043 (P=0.0101). In a second step, we added support to the association at DXS8043 using additional markers, additional subjects and a haplotype-based analysis (best obtained P-value=0.00001). These results provide support for the existence of a locus on the X chromosome that predisposes the FC to autism spectrum disorders.

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References

  1. DSM-IV. Diagnostic and Statistical Manual of Mental Diseases, 4th edn. American pshychiatric association, 1994.

  2. Tanguay PE . Pervasive developmental disorders: a 10-year review. J Am Acad Child Adolesc Psychiatry 2000; 39: 1079–1095.

    Article  CAS  Google Scholar 

  3. Bristol MM, Cohen DJ, Costello EJ, Denckla M, Eckberg TJ, Kallen R et al. State of the science in autism: report to the National Institutes Health. J Autism Dev Disord 1996; 26: 121–154.

    Article  CAS  Google Scholar 

  4. Fombonne E . Epidemiological trends in rates of autism. Mol Psychiatry 2002; 7 (Suppl 2): S4–6.

    Article  Google Scholar 

  5. Fombonne E . Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003; 33: 365–382.

    Article  Google Scholar 

  6. Lauritsen M, Ewald H . The genetics of autism. Acta Psychiatr Scand 2001; 103: 411–427.

    Article  CAS  Google Scholar 

  7. Muhle R, Trentacoste SV, Rapin I . The genetics of autism. Pediatrics 2004; 113: e472–e486.

    Article  Google Scholar 

  8. Cohen DJ, Volkmar FR . Handbook of autism and pervasive developmental disorders. 2nd edn, John Wiley & Sons Inc.: New York, 1997.

    Google Scholar 

  9. Vincent JB, Melmer G, Bolton PF, Hodgkinson S, Holmes D, Curtis D et al. Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region. Psychiatr Genet 2005; 15: 83–90.

    Article  Google Scholar 

  10. Gauthier J, Bonnel A, St-Onge J, Karemera L, Laurent S, Mottron L et al. NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am J Med Genet B Neuropsychiatr Genet 2005; 132: 74–75.

    Article  Google Scholar 

  11. Vincent JB, Kolozsvari D, Roberts WS, Bolton PF, Gurling HM, Scherer SW . Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. Am J Med Genet B Neuropsychiatr Genet 2004; 129B: 82–84.

    Article  Google Scholar 

  12. Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 2004; 74: 552–557.

    Article  CAS  Google Scholar 

  13. Lam CW, Yeung WL, Ko CH, Poon PM, Tong SF, Chan KY et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet 2000; 37: E41.

    Article  CAS  Google Scholar 

  14. Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML et al. Identification of MeCP2 mutations in a series of females with autistic disorder. Pediatr Neurol 2003; 28: 205–211.

    Article  Google Scholar 

  15. Shibayama A, Cook Jr EH, Feng J, Glanzmann C, Yan J, Craddock N et al. MECP2 structural and 3′-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. Am J Med Genet B Neuropsychiatr Genet 2004; 128: 50–53.

    Article  Google Scholar 

  16. Shinahara K, Saijo T, Mori K, Kuroda Y . Single-strand conformation polymorphism analysis of the FMR1 gene in autistic and mentally retarded children in Japan. J Med Invest 2004; 51: 52–58.

    Article  Google Scholar 

  17. Turner G, Partington M, Kerr B, Mangelsdorf M, Gecz J . Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. Am J Med Genet 2002; 112: 405–411.

    Article  Google Scholar 

  18. Shao Y, Wolpert CM, Raiford KL, Menold MM, Donnelly SL, Ravan SA et al. Genomic screen and follow-up analysis for autistic disorder. Am J Med Genet 2002; 114: 99–105.

    Article  Google Scholar 

  19. Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M, Sponheim E et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805–812.

    Article  CAS  Google Scholar 

  20. Liu J, Nyholt DR, Magnussen P, Parano E, Pavone P, Geschwind D et al. A genomewide screen for autism susceptibility loci. Am J Hum Genet 2001; 69: 327–340.

    Article  CAS  Google Scholar 

  21. Auranen M, Vanhala R, Varilo T, Ayers K, Kempas E, Ylisaukko-Oja T et al. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25–27. Am J Hum Genet 2002; 71: 777–790.

    Article  Google Scholar 

  22. Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003; 73: 886–897.

    Article  CAS  Google Scholar 

  23. Schutz CK, Polley D, Robinson PD, Chalifoux M, Macciardi F, White BN et al. Autism and the X chromosome: No linkage to microsatellite loci detected using the affected sibling pair method. Am J Med Genet 2002; 109: 36–41.

    Article  Google Scholar 

  24. Davignon J, Roy M . Familial hypercholesterolemia in French-Canadians: taking advantage of the presence of a ‘founder effect’. Am J Cardiol 1993; 72: 6D–10D.

    Article  CAS  Google Scholar 

  25. Heyer E, Tremblay M . Variability of the genetic contribution of Quebec population founders associated to some deleterious genes. Am J Hum Genet 1995; 56: 970–978.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Simard LR, Prescott G, Rochette C, Morgan K, Lemieux B, Mathieu J et al. Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French-Canadian population. Hum Mol Genet 1994; 3: 459–463.

    Article  CAS  Google Scholar 

  27. Lord C, Rutter M, Le Couteur A . Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994; 24: 659–685.

    Article  CAS  Google Scholar 

  28. Lord C, Cook EH, Leventhal BL, Amaral DG . Autism spectrum disorders. Neuron 2000; 28: 355–363.

    Article  CAS  Google Scholar 

  29. Berument SK, Rutter M, Lord C, Pickles A, Bailey A . Autism screening questionnaire: diagnostic validity. Br J Psychiatry 1999; 175: 444–451.

    Article  CAS  Google Scholar 

  30. Dudbridge F . Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115–121.

    Article  Google Scholar 

  31. Dudbridge F, Koeleman BP, Todd JA, Clayton DG . Unbiased application of the transmission/disequilibrium test to multilocus haplotypes. Am J Hum Genet 2000; 66: 2009–2012.

    Article  CAS  Google Scholar 

  32. Koeleman BP, Herr MH, Zavattari P, Dudbridge F, March R, Campbell D et al. Conditional ETDT analysis of the human leukocyte antigen region in type 1 diabetes. Ann Hum Genet 2000; 64: 215–221.

    Article  CAS  Google Scholar 

  33. Redolfi E, Montagna C, Mumm S, Affer M, Susani L, Reinbold R et al. Identification of CXorf1, a novel intronless gene in Xq27.3, expressed in human hippocampus. DNA Cell Biol 1998; 17: 1009–1016.

    Article  CAS  Google Scholar 

  34. Schumann CM, Hamstra J, Goodlin-Jones BL, Lotspeich LJ, Kwon H, Buonocore MH et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 2004; 24: 6392–6401.

    Article  CAS  Google Scholar 

  35. Raymond GV BM, Kemper TL . Hippocampus in AD: a Golgi analysis. Acta Neuropathol (Berl) 1996; 91: 117–119.

    Article  CAS  Google Scholar 

  36. Aruga J, Yokota N, Mikoshiba K . Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue. Gene 2003; 315: 87–94.

    Article  CAS  Google Scholar 

  37. Aruga J, Mikoshiba K . Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Mol Cell Neurosci 2003; 24: 117–129.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all the families who made this research possible by participating in our study. Claude Marineau and Dr Lan Xiong for helpful discussions and comments. Thanks to Dominique Verlaan for carefully reading the manuscript. We also thank Daniel Rochefort for technical help. This work was supported by the Canadian Institutes for Health Research.

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Authors and Affiliations

  1. Centre Hospitalier de l'Université de Montréal, Research Centre, Notre Dame Hospital, Montreal, QC, Canada

    J Gauthier, J St-Onge, A Bonnel, D Gariépy, S Laurent, R Najafee, H Lacasse & G A Rouleau

  2. Department of Biology, McGill University, Montreal, QC, Canada

    J Gauthier

  3. Department of Psychiatry, McGill University and Douglas Hospital Research Centre, Montreal, QC, Canada

    R Joober

  4. Department of Medicine, Université de Montréal and Institut de cardiologie de Montréal, Montreal, QC, Canada

    M-P Dubé

  5. Centre de réadaptation en déficience intellectuelle du Bas St-Laurent, Rivière-du-Loup, QC, Canada

    L St-Charles

  6. Department of Psychiatry, McGill University and Montreal Children's Hospital, Montreal, QC, Canada

    É Fombonne

  7. Department of Psychiatry, Université de Montréal and Rivières-des-Prairies Hospital, Montreal, QC, Canada

    L Mottron

  8. Department of Medicine, Université de Montréal, Montreal, QC, Canada

    G A Rouleau

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  1. J Gauthier
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  2. R Joober
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  3. M-P Dubé
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  4. J St-Onge
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  5. A Bonnel
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  6. D Gariépy
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  7. S Laurent
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  8. R Najafee
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  9. H Lacasse
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  10. L St-Charles
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  11. É Fombonne
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  12. L Mottron
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  13. G A Rouleau
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Corresponding author

Correspondence to G A Rouleau.

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Gauthier, J., Joober, R., Dubé, MP. et al. Autism spectrum disorders associated with X chromosome markers in French-Canadian males. Mol Psychiatry 11, 206–213 (2006). https://doi.org/10.1038/sj.mp.4001756

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  • DOI: https://doi.org/10.1038/sj.mp.4001756

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