Skip to main content

Advertisement

SpringerLink
Log in

Linkage analyses of chromosomal region 18p11-q12 in dyslexia

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Dyslexia is characterized as a significant impairment in reading and spelling ability that cannot be explained by low intelligence, low school attendance or deficits in sensory acuity. It is known to be a hereditary disorder that affects about 5% of school aged children, making it the most common of childhood learning disorders. Several susceptibility loci have been reported on chromosomes 1, 2, 3, 6, 15, and 18. The locus on chromosome 18 has been described as having the strongest influence on single word reading, phoneme awareness, and orthographic coding in the largest genome wide linkage study published to date (Fisher et al., 2002). Here we present data from 82 German families in order to investigate linkage of various dyslexia-related traits to the previously described region on chromosome 18p11-q12. Using two- and multipoint analyses, we did not find support for linkage of spelling, single word reading, phoneme awareness, orthographic coding and rapid naming to any of the 14 genotyped STR markers. Possible explanations for our non-replication include differences in study design, limited power of our study and overestimation of the effect of the chromosome 18 locus in the original study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • L Abel B Müller-Myhsok (1998) ArticleTitleRobustness and power of the maximum-likelihood-binomial and maximum-likelihood-score methods, in multipoint linkage analysis of affected-sibship data. Am J Hum Genet 63 638–647 Occurrence Handle1:STN:280:DyaK1czkvF2rtQ%3D%3D Occurrence Handle9683590

    CAS  PubMed  Google Scholar 

  • LR Cardon SD Smith DW Fulker WJ Kimberling BF Pennington JC DeFries (1994) ArticleTitleQuantitative trait locus for reading disability on chromosome 6. Science 266 276–279 Occurrence Handle1:CAS:528:DyaK2cXmslemurw%3D Occurrence Handle7939663

    CAS  PubMed  Google Scholar 

  • NH Chapman WH Raskind JB Thomson VW Berninger EM Wijsman (2003) ArticleTitleSegregation analysis of phenotypic components of learning disabilities. II. Phonological decoding. Am J Med Genet 121 60–70

    Google Scholar 

  • NH Chapman RP Igo JB Thomson M Matsushita Z Brkanac T Holzman VW Berninger EM Wijsman WH Raskind (2004) ArticleTitleLinkage analyses of four regions previously implicated in dyslexia: confirmation of a locus on chromosome 15q. Am J Med Genet 15 67–75

    Google Scholar 

  • DeFries JC, Gillis JJ (1993) Genetics of reading disability. In: Plomin R, McClearn GF (eds) Nature, nurture and psychology. APA Books, New Nork, pp 121–145

  • MB Denckla R Rudel (1974) ArticleTitleRapid “automatized” naming of pictured objects, colors, letters and numbers by normal children. Cortex 10 186–202 Occurrence Handle1:STN:280:CSuB1c7hsVw%3D Occurrence Handle4844470

    CAS  PubMed  Google Scholar 

  • Dilling H, Mombour W, Schmidt MH (1991) International classification of mental diseases, ICD-10, german edn. Huber, Bern

  • T Fagerheim P Raeymaekers FE Tonnessen M Pedersen L Tranebjaerg HA Lubs (1999) ArticleTitleA new gene (DYX3) for dyslexia is located on chromosome 2. J Med Genet 36 664–669 Occurrence Handle1:STN:280:DyaK1MvjsFGkug%3D%3D Occurrence Handle10507721

    CAS  PubMed  Google Scholar 

  • SE Fisher JC DeFries (2002) ArticleTitleDevelopmental dyslexia: genetic dissection of a complex cognitive trait. Nat Rev Neurosci 3 767–780 Occurrence Handle10.1038/nrn936 Occurrence Handle1:CAS:528:DC%2BD38XnsVGqtbc%3D Occurrence Handle12360321

    Article  CAS  PubMed  Google Scholar 

  • SE Fisher AJ Marlow J Lamb E Maestrini DF Williams AJ Richardson DE Weeks JF Stein AP Monaco (1999) ArticleTitleA quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia. Am J Hum Genet 64 146–156 Occurrence Handle10.1086/302190 Occurrence Handle1:CAS:528:DyaK1MXht1elsrY%3D Occurrence Handle9915953

    Article  CAS  PubMed  Google Scholar 

  • SE Fisher C Francks AJ Marlow IL MacPhie DF Newbury LR Cardon Y Ishikawa-Brush AJ Richardson JB Talcott J Gayan RK Olson BF Pennington SD Smith JC DeFries JF Stein AP Monaco (2002) ArticleTitleIndependent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat Genet 30 86–91 Occurrence Handle10.1038/ng792 Occurrence Handle1:CAS:528:DC%2BD38XivVCqsQ%3D%3D Occurrence Handle11743577

    Article  CAS  PubMed  Google Scholar 

  • J Gayan SD Smith SS Cherny LR Cardon DW Fulker AM Brower RK Olson BF Pennington JC DeFries (1999) ArticleTitleQuantitative-trait locus for specific language and reading deficits on chromosome 6p. Am J Hum Genet 64 157–164 Occurrence Handle1:CAS:528:DyaK1MXht1elsrc%3D Occurrence Handle9915954

    CAS  PubMed  Google Scholar 

  • JW Gilger IB Borecki JC DeFries BF Pennington (1994) ArticleTitleCommingling and segregation analysis of reading performance in families of normal reading probands. Behav Genet 24 345–355 Occurrence Handle10.1007/BF01067536 Occurrence Handle1:STN:280:ByqD1crltlY%3D Occurrence Handle7993313

    Article  CAS  PubMed  Google Scholar 

  • EL Grigorenko FB Wood MS Meyer LA Hart WC Speed A Shuster DL Pauls (1997) ArticleTitleSusceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. Am J Hum Genet 60 27–39 Occurrence Handle1:CAS:528:DyaK2sXlvFKltQ%3D%3D Occurrence Handle8981944

    CAS  PubMed  Google Scholar 

  • EL Grigorenko FB Wood MS Meyer JE Pauls LA Hart DL Pauls (2001) ArticleTitleLinkage studies suggest a possible locus for developmental dyslexia on chromosome 1p. Am J Med Genet 105 120–129 Occurrence Handle10.1002/1096-8628(20010108)105:1<120::AID-AJMG1075>3.0.CO;2-T Occurrence Handle1:STN:280:DC%2BD3Mzmtlehsw%3D%3D Occurrence Handle11424982

    Article  CAS  PubMed  Google Scholar 

  • EL Grigorenko FB Wood L Golovyan M Meyer C Romano D Pauls (2003) ArticleTitleContinuing the search for dyslexia genes on 6p. Am J Med Genet 118 89–98

    Google Scholar 

  • JK Haseman RC Elston (1972) ArticleTitleThe investigation of linkage between a quantitative trait and a marker locus. Behav Genet 2 3–19 Occurrence Handle10.1007/BF01066731 Occurrence Handle1:STN:280:CSyB3Mzgs1w%3D Occurrence Handle4157472

    Article  CAS  PubMed  Google Scholar 

  • N Kaminen K Hannula-Jouppi M Kestila P Lahermo K Muller M Kaaranen B Myllyluoma A Voutilainen H Lyytinen J Nopola-Hemmi J Kere (2003) ArticleTitleA genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32. J Med Genet 40 340–345 Occurrence Handle10.1136/jmg.40.5.340 Occurrence Handle1:CAS:528:DC%2BD3sXmt1GksLg%3D Occurrence Handle12746395

    Article  CAS  PubMed  Google Scholar 

  • DE Kaplan J Gayan J Ahn TW Won D Pauls RK Olson JC DeFries F Wood BF Pennington GP Page SD Smith JR Gruen (2002) ArticleTitleEvidence for linkage and association with reading disability on 6p21.3–22. Am J Hum Genet 70 1287–1298 Occurrence Handle10.1086/340449 Occurrence Handle1:CAS:528:DC%2BD38XjsFGnsL8%3D Occurrence Handle11951179

    Article  CAS  PubMed  Google Scholar 

  • L Kruglyak MJ Daly MP Reeve-Daly ES Lander (1996) ArticleTitleParametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 58 1347–1363 Occurrence Handle1:CAS:528:DyaK28XjslaktLo%3D Occurrence Handle8651312

    CAS  PubMed  Google Scholar 

  • E Lander L Kruglyak (1995) ArticleTitleGenetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11 241–247 Occurrence Handle10.1038/ng1195-241 Occurrence Handle1:CAS:528:DyaK2MXptlSjs74%3D Occurrence Handle7581446

    Article  CAS  PubMed  Google Scholar 

  • Landerl K, Wimmer H, Moser E (1997) Salzburger Lese- und Rechtschreibtest. Huber, Bern

  • BA Lewis NJ Cox PJ Byard (1993) ArticleTitleSegregation analysis of speech and language disorders. Behav Genet 23 291–297 Occurrence Handle10.1007/BF01082469 Occurrence Handle1:STN:280:ByyA2MnntFI%3D Occurrence Handle8352725

    Article  CAS  PubMed  Google Scholar 

  • FI Lewitter JC DeFries RC Elston (1980) ArticleTitleGenetic models of reading disability. Behav Genet 10 9–30 Occurrence Handle10.1007/BF01067316 Occurrence Handle1:STN:280:Bi6D3sfntlc%3D Occurrence Handle7425998

    Article  CAS  PubMed  Google Scholar 

  • C Marino R Giorda L Vanzin M Nobile ML Lorusso C Baschirotto L Riva M Molteni M Battaglia (2004) ArticleTitleA locus on 15q15-15qter influences dyslexia: further support from a transmission/disequilibrium study in an Italian speaking population. J Med Genet 41 42–46 Occurrence Handle10.1136/jmg.2003.010603 Occurrence Handle1:CAS:528:DC%2BD2cXhs1KhsLg%3D Occurrence Handle14729831

    Article  CAS  PubMed  Google Scholar 

  • DW Morris L Robinson D Turic M Duke V Webb C Milham E Hopkin K Pound S Fernando M Easton M Hamshere N Williams P McGuffin J Stevenson M Krawczak MJ Owen MC O’Donovan J Williams (2000) ArticleTitleFamily-based association mapping provides evidence for a gene for reading disability on chromosome 15q. Hum Mol Genet 22 843–848

    Google Scholar 

  • J Nopola-Hemmi B Myllyluoma T Haltia M Taipale V Ollikainen T Ahonen A Voutilainen J Kere E Widen (2001) ArticleTitleA dominant gene for developmental dyslexia on chromosome 3. J Med Genet 38 658–664 Occurrence Handle10.1136/jmg.38.10.658 Occurrence Handle1:CAS:528:DC%2BD3MXotVemurs%3D Occurrence Handle11584043

    Article  CAS  PubMed  Google Scholar 

  • JR O’Connell DE Weeks (1998) ArticleTitlePedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63 259–266 Occurrence Handle1:STN:280:DyaK1c3pvFyhsA%3D%3D Occurrence Handle9634505

    CAS  PubMed  Google Scholar 

  • M Rabin XL Wen M Hepburn HA Lubs E Feldman R Duara (1993) ArticleTitleSuggestive linkage of developmental dyslexia to chromosome 1p34-p36. Lancet 342 178 Occurrence Handle10.1016/0140-6736(93)91384-X Occurrence Handle1:STN:280:ByyA38zmsVA%3D Occurrence Handle8101276

    Article  CAS  PubMed  Google Scholar 

  • P Royston DG Altman (1994) ArticleTitleRegression using fractional polynomials of continuous covariats: parsimonious parametric modelling. Applied Statistics 43 429–467

    Google Scholar 

  • M Rutter A Caspi D Fergusson LJ Horwood R Goodman B Maughan TE Moffitt H Meltzer J Carroll (2004) ArticleTitleSex differences in developmental reading disability: new findings from 4 epidemiological studies. JAMA 291 2007–2012 Occurrence Handle10.1001/jama.291.16.2007 Occurrence Handle1:CAS:528:DC%2BD2cXjs1aisLY%3D Occurrence Handle15113820

    Article  CAS  PubMed  Google Scholar 

  • G Schulte-Körne (2001a) ArticleTitleAnnotation: Genetics of reading and spelling disorder. J Child Psychol Psychiatry 42 985–997

    Google Scholar 

  • Schulte-Körne G (2001b) Legasthenie und Sprachwahrnehmung. Waxmann, Münster

  • G Schulte-Körne W Deimel K Muller C Gutenbrunner H Remschmidt (1996) ArticleTitleFamilial aggregation of spelling disability. J Child Psychol Psychiatry 37 817–822 Occurrence Handle8923224

    PubMed  Google Scholar 

  • G Schulte-Körne T Grimm MM Nöthen B Müller-Myhsok S Cichon IR Vogt P Propping H Remschmidt (1998) ArticleTitleEvidence for linkage of spelling disability to chromosome 15. Am J Hum Genet 63 279–282 Occurrence Handle10.1086/301919 Occurrence Handle9634517

    Article  PubMed  Google Scholar 

  • G Schulte-Körne W Deimel H Remschmidt (2001) ArticleTitleDiagnosis of reading and spelling disorder. Z Kinder Jugendpsychiatr Psychother 29 113–116 Occurrence Handle11393049

    PubMed  Google Scholar 

  • G Schulte-Körne W Deimel M Jungermann H Remschmidt (2003) ArticleTitleFollow-up of a sample of children with reading-spelling disorders in adulthood. Z Kinder Jugendpsychiatr Psychother 31 267–276 Occurrence Handle14694843

    PubMed  Google Scholar 

  • G Schulte-Körne J Bartling W Deimel H Remschmidt (2004) ArticleTitleVisual evoked potential elicited by coherenty moving dots in dyslexic children. Neurosci Lett 357 207–210 Occurrence Handle15003286

    PubMed  Google Scholar 

  • SE Shaywitz JM Fletcher JM Holahan AE Shneider KE Marchione KK Stuebing DJ Francis KR Pugh BA Shaywitz (1999) ArticleTitlePersistence of dyslexia: the Connecticut Longitudinal Study at adolescence. Pediatrics 104 1351–1359 Occurrence Handle10.1542/peds.104.6.1351 Occurrence Handle1:STN:280:DC%2BD3c%2FlsVOnuw%3D%3D Occurrence Handle10585988

    Article  CAS  PubMed  Google Scholar 

  • Unnewehr S, Schneider S, Margraf J (1995) Kinder-DIPS – Diagnostisches Interview bei psychischen Störungen im Kindes- und Jugendalter. Hogrefe, Göttingen

  • Weiß RH (1998) Grundintelligenztest Skala 2 (CFT 20), 3. Aufl. Hogrefe, Göttingen

  • Weiß RH, Osterland J (1997) Grundintelligenztest Skala 1 (CFT 1). Hogrefe, Göttingen

  • EM Wijsman D Peterson AL Leutenegger JB Thomson KA Goddard L Hsu VW Berninger WH Raskind (2000) ArticleTitleSegregation analysis of phenotypic components of learning disabilities. I. Nonword memory and digit span. Am J Hum Genet 67 631–646 Occurrence Handle10.1086/303044 Occurrence Handle1:STN:280:DC%2BD3cvktFentw%3D%3D Occurrence Handle10924405

    Article  CAS  PubMed  Google Scholar 

  • EG Willcutt BF Pennington SD Smith LR Cardon J Gayan VS Knopik RK Olson JC DeFries (2002) ArticleTitleQuantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/ hyperactivity disorder. Am J Med Genet 114 260–268 Occurrence Handle10.1002/ajmg.10205 Occurrence Handle11920845

    Article  PubMed  Google Scholar 

  • A Ziegler (1999) ArticleTitleSampling strategies for model free linkage analyses of quantitative traits: implications for sib pair studies of reading and spelling disabilities to minimize the total study cost. Eur Child Adolesc Psychiatry 3 35–39

    Google Scholar 

  • A Ziegler IR König W Deimel E Plume MM Nöthen P Propping A Kleensang B Müller-Myhsok A Warnke H Remschmidt G Schulte-Körne (2005) ArticleTitleDevelopmental dyslexia – recurrence risk estimates from a German bi-center study using the single proband sib pair design. Hum Hered 59 136–143 Occurrence Handle10.1159/000085572 Occurrence Handle15867474

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Humangenetik, Lübeck, Germany

    J. Schumacher, P. Propping, M. Manthey & M. Duell

  2. Department of Genomics, Life & Brain Center, Universität Bonn, Lübeck, Germany

    M. M. Nöthen

  3. Institut für Medizinische Biometrie und Statistik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck, Lübeck, Germany

    I. R. König, A. Kleensang, D. Repsilber & A. Ziegler

  4. Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Philipps-Universität Marburg, Marburg, Germany

    M. Preis, H. Remschmidt & G. Schulte-Körne

  5. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany

    E. Plume & A. Warnke

Authors
  1. J. Schumacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. R. König
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Plume
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Propping
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Warnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Manthey
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Duell
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Kleensang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. Repsilber
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Preis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H. Remschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. Ziegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. M. Nöthen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. G. Schulte-Körne
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schumacher, J., König, I., Plume, E. et al. Linkage analyses of chromosomal region 18p11-q12 in dyslexia. J Neural Transm 113, 417–423 (2006). https://doi.org/10.1007/s00702-005-0336-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0336-y

Search

Navigation