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Evidence for allelic association on chromosome 3q25–27 in families with autism spectrum disorders originating from a subisolate of Finland

Molecular Psychiatry volume 8, pages 879–884 (2003)Cite this article

Abstract

Recent molecular studies on autism and related disorders have supported a multilocus etiology for the disease spectrum. To maximize genetic and cultural homogeneity, we have focused our molecular studies to families originating from a subisolate of Central Finland. Genealogical studies enabled the identification of a megapedigree comprising of 12 core families with autism and Asperger syndrome (AS). We analyzed two chromosomal regions on Iq and 3q showing highest lod scores in our genome-wide scan, as well as the AUTS1 locus on chromosome 7q. For markers on 3q25–27, more significant association was observed in families from subisolate compared to families from the rest of Finland. In contrast, no clear evidence for association on AUTS1 locus was obtained. The wide interval showing association, in particular, on chromosome 3q suggests a locus for autism spectrum of disorders on this chromosomal region.

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References

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

    Article  PubMed  PubMed Central  Google Scholar 

  2. IMGSAC (International Molecular Genetic Study of Autism Consortium). Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet 2001; 10: 973–982.

  3. Bailey A, Phillips W, Rutter M . Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. Child Psychol Psychiatry Allied Disciplines 1996; 37: 89–126.

    Article  CAS  Google Scholar 

  4. Folstein S, Rutter M . Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18: 297–321.

    Article  CAS  PubMed  Google Scholar 

  5. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G et al. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989; 30: 405–416.

    Article  CAS  PubMed  Google Scholar 

  6. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25: 63–77.

    Article  CAS  PubMed  Google Scholar 

  7. Bailey A, Palferman S, Heavey L, Le Couteur A . Autism: the phenotype in relatives. J Autism Dev Disorders 1998; 28: 369–392.

    Article  CAS  Google Scholar 

  8. Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH et al. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am J Hum Genet 1995; 57: 717–726.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Folstein SE, Rosen-Sheidley B . Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2001; 2: 943–955.

    Article  CAS  PubMed  Google Scholar 

  10. IMGSAC (International Molecular Genetic Study of Autism Consortium). A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium. Hum Mol Genet 1998; 7: 571–578.

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

    Article  CAS  PubMed  Google Scholar 

  12. Barrett S, Beck JC, Bernier R, Bisson E, Braun TA, Casavant TL et al. An autosomal genomic screen for autism. Am J Med Genet 1999; 88: 609–615.

    Article  CAS  PubMed  Google Scholar 

  13. Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D, Hallmayer J et al. A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 1999; 65: 493–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Buxbaum JD, Silverman JM, Smith CJ, Kilifarski M, Reichert J, Hollander E et al. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. Am J Hum Genet 2001; 68: 1514–1520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. IMGSAC (International Molecular Genetic Study of Autism Consortium). A genome wide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p. Am J Hum Genet 2001; 69: 570–581.

  17. 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  PubMed  Google Scholar 

  18. Varilo T, Paunio T, Parker A, Perola M, Meyer J, Terwilliger JD, Peltonen L . The interval of linkage disequilibrium (LD) detected with microsatellite and SNP markers in chromosomes of Finnish populations with different histories. Hum Mol Genet 2003; 12: 51–59.

    Article  CAS  PubMed  Google Scholar 

  19. Nevanlinna HR . The Finnish population structure. A genetic and genealogical study. Hereditas 1972; 71: 195–236.

    Article  CAS  PubMed  Google Scholar 

  20. Nystrom-Lahti M, Sistonen P, Mecklin JP, Pylkkanen L, Aaltonen LA, Jarvinen H et al. Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc Natl Acad Sci USA 1994; 91: 6054–6058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Moisio AL, Sistonen P, Weissenbach J, de la Chapelle A, Peltomaki P . Age and origin of two common MLH1 mutations predisposing to hereditary colon cancer. Am J Hum Genet 1996; 59: 1243–1251.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ehlers S, Gillberg C . The epidemiology of Asperger syndrome. A total population study. J Child Psychol Psychiatry Allied Disciplines 1993; 34: 1327–1350.

    Article  CAS  Google Scholar 

  23. World Health Organization. International Classification of Diseases, 10th edn, Chapter 5. Mental and Behavioural Disorders. Diagnostic Criteria for Research. Geneva: WHO, 1993.

  24. Blin N, Stafford DW . A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res 1976; 3: 2303–2308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. O' Connell JR, Weeks DE . PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.

    Article  CAS  Google Scholar 

  26. Sobel E, Lange K . Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 1996; 58: 1323–1337.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lange K, Weeks D, Boehnke M . Programs for pedigree analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol 1988; 5: 471–472.

    Article  CAS  PubMed  Google Scholar 

  28. Lange K, Cantor R, Horvath S, Perola M, Sabatti C, Sinsheimer JS et al. MENDEL version 4.0: A computer package for the exact genetic analysis of discrete traits in pedigree and population data sets. Am J Hum Genet 2001; 69 (Suppl 4): 505.

    Google Scholar 

  29. Sinsheimer JS, Blangero J, Lange K . Gamete-competition models. Am J Hum Genet 2000; 66: 1168–1172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Goring HH, Terwilliger JD . Linkage analysis in the presence of errors IV: joint pseudomarker analysis of linkage and/or linkage disequilibrium on a mixture of pedigrees and singletons when the mode of inheritance cannot be accurately specified. Am J Hum Genet 2000; 66: 1310–1327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lathrop GM, Lalouel JM, Julier C, Ott J . Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 1984; 81: 3443–3446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cottingham Jr RW, Idury RM, Schaffer AA . Faster sequential genetic linkage computations. Am J Hum Genet 1993; 53: 252–263.

    PubMed  PubMed Central  Google Scholar 

  33. Schaffer AA, Gupta SK, Shriram K, Cottingham Jr RW . Avoiding recomputation in linkage analysis. Hum Hered 1994; 44: 225–237.

    Article  CAS  PubMed  Google Scholar 

  34. Lange K . Mathematical and Statistical Methods for Genetic Analysis, 2nd edn. New York: Springer-Verlag, 2002.

    Book  Google Scholar 

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Acknowledgements

We thank the families for the participation in this study and the child neurologists who referred patients and provided information. Drs Kenneth Lange and Janet Sinsheimer are thanked for their valuable advice concerning the data analysis. Financial support of the Academy of Finland, The Rinnekoti Research Foundation, The Pediatric Research Foundation (Ulla Hjelt Fond), Maud Kuistila Foundation and the Finnish Medical Association is acknowledged. KA is supported by the Cure Autism Now Foundation. These study protocols have been approved by the Ethical Committees of the Hospital for Children and Adolescents of Helsinki University Hospital and National Public Health Institute, Helsinki. Informed consent for genetic studies was obtained from the subjects and/or their parents.

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Authors and Affiliations

  1. Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

    M Auranen, T Varilo, E Kempas, T Ylisaukko-oja, L Peltonen & I Järvelä

  2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland

    M Auranen, T Varilo, E Kempas, T Ylisaukko-oja, L Peltonen & I Järvelä

  3. Unit of Child Neurology, Central Hospital of Central Finland, Jyväskylä, Finland

    R Alen

  4. Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki, Finland

    R Vanhala

  5. Department of Biomathematics, UCLA School of Medicine, LA, USA

    K Ayers

  6. Department of Human Genetics, UCLA School of Medicine, LA, USA

    L Peltonen

  7. Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki, Finland

    I Järvelä

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  1. M Auranen
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  2. T Varilo
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  4. R Vanhala
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  8. L Peltonen
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  9. I Järvelä
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Correspondence to M Auranen.

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Auranen, M., Varilo, T., Alen, R. et al. Evidence for allelic association on chromosome 3q25–27 in families with autism spectrum disorders originating from a subisolate of Finland. Mol Psychiatry 8, 879–884 (2003). https://doi.org/10.1038/sj.mp.4001299

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  • DOI: https://doi.org/10.1038/sj.mp.4001299

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