Advertisement

Behavior Genetics

, Volume 41, Issue 1, pp 43–49 | Cite as

Familial Dyslexia in a Large Swedish Family: A Whole Genome Linkage Scan

  • Idor SvenssonEmail author
  • Staffan Nilsson
  • Jan Wahlström
  • Margareta Jernås
  • Lena M. Carlsson
  • Erland Hjelmquist
ORIGINAL RESEARCH

Abstract

There is a compelling body of evidence that developmental dyslexia runs in families and seems to be highly inheritable. Several investigations during the last two decades have shown possible locations of genes that might be involved in dyslexia, including regions of chromosomes 1, 2, 3, 6, 11, 13, 15 and 18. In addition, six candidate genes (KIAA0319, DYX1C1, DCDC2, ROBO1, MRPL19 and C2ORF3) seem to be related to dyslexia. The present study carried out a whole genome scan in a six-generation pedigree. In addition to literacy skills the assessment included cognitive skills and records concerning the history of reading and writing ability. Thirty-five percent were regarded as dyslexic in the family. A linkage analysis using both a quantitative and a qualitative approach has been performed. No evidence was obtained to support the hypothesis that the transmission of dyslexia in this pedigree is due to a highly penetrant major gene, and previous linkage findings were not replicated; however, power in this small study was not adequate to confirm linkage of genes with small to moderate effects. The results were discussed in relation to diagnostic procedures and sample characteristics.

Keywords

Dyslexia Heredity Linkage Chromosomes Genes 

References

  1. Almasy L, Blangero J (1998) Multipoint quantitative trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211CrossRefPubMedGoogle Scholar
  2. Anthoni H, Zucchelli M, Matsson H et al (2007) A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia. Hum Mol Genet 16:667–677CrossRefPubMedGoogle Scholar
  3. Barr L, Couto M (2007) Molecular genetics of reading. In Grigorenko E, Naples AJ (eds) Single word reading: behavioural and biological perspectives. Psychology Press, pp 255–281Google Scholar
  4. Bates TC, Luciano M, Castles A, Coltheart M, Wright MJ, Martin NG (2007) Replication of reported linkage for dyslexia and spelling and suggestive evidence for novel regions on chromosomes 4 and 17. Eur J Hum Genet 15:194–203CrossRefPubMedGoogle Scholar
  5. Brkanac Z, Chapman NH, Matsushita MM, Chun L, Nielsen K, Cochrane E et al (2007) Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia. Am J Med Genet B 144b:556–560CrossRefGoogle Scholar
  6. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC (1994) Quantitative trait locus for reading disability on chromosome 6. Science 266:276–279CrossRefPubMedGoogle Scholar
  7. Cope NA, Hill G, Moskvina V, Stevensen J, Holmans P, Owen MJ et al (2005a) Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. Am J Hum Genet 76:581–591CrossRefPubMedGoogle Scholar
  8. Cope NA, Hill G, van den Bree M, Harold D, Moskvina V, Green EK et al (2005b) No support for association between dyslexia susceptibility 1 candidate 1 and developmental dyslexia. Mol Psychiatry 10:237–238CrossRefPubMedGoogle Scholar
  9. de Kovel CGF, Franke B, Hol FA, Lebrec JJP, Maassen B, Brunner H et al (2008) Confirmation of dyslexia susceptibility loci on chromosomes 1p and 2p, but not 6p in a Dutch sib-pair collection. Am J Med Genet B 147b:294–300CrossRefGoogle Scholar
  10. DeFries JC, Gillis JJ (1993) Genetics of reading disabilities. In: Plomin R, McClearn G (eds) Nature, nurture, and psychology. APA Press, Washington, DC, pp 121–145CrossRefGoogle Scholar
  11. Fagerheim T, Raeymaekers P, Tønnessen FE, Pedersen M, Tranebjærg L, Lubs HA (1999) A new gene (DYX3) for dyslexia is located on chromosome 2. J Med Genet 36:664–669PubMedGoogle Scholar
  12. Field LL, Kaplan BJ (1998) Absence of linkage of phonological coding dyslexia to chromosome 6p23–p21.3 in a large data set. Am J Hum Genet 63:1448–1456CrossRefPubMedGoogle Scholar
  13. Fisher SE, DeFries JC (2002) Developmental dyslexia: genetic dissection of a complex cognitive trait. Nat Neurosci 3:767–780Google Scholar
  14. Fisher SE, Smith SD (2001) Progress towards the identification of genes influencing developmental dyslexia. In: Fawcett AJ (ed) Dyslexia: theory and good practice. Whurr, London, pp 39–64Google Scholar
  15. Fisher SE, Marlow AJ, Lamb J, Maestrini E, Williams DF, Richardson AJ et al (1999) A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia. Am J Hum Genet 64:146–156CrossRefPubMedGoogle Scholar
  16. Fisher SE, Francks C, Marlow AJ, MacPhie L, Newbury DF, Cardon LR et al (2002) Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat Genet 30:86–91CrossRefPubMedGoogle Scholar
  17. Frost J, Madsbjerg S, Niedersøe J, Olofsson Å, Sørensen PM (2005) Semantic and phonological skills in predicting reading development: from 3–16 years of age. Dyslexia 11:79–92CrossRefPubMedGoogle Scholar
  18. Gathercole SE (2006) Nonword repetition and word learning: the nature of the relationship. Appl Psycholinguist 27:513–543Google Scholar
  19. Gayán J, Olson RK (2003) Genetic and environmental influences on individual differences in printed word recognition. J Exp Child Psychol 84:97–123CrossRefPubMedGoogle Scholar
  20. Grigorenko EL (2001) Developmental dyslexia: an update on genes, brains, and environments. J Child Psychol Psychiatry 42:91–125CrossRefPubMedGoogle Scholar
  21. Grigorenko EL (2005) A conservative meta-analysis of linkage and linkage-association studies of developmental dyslexia. Sci Stud Read 9:285–316CrossRefGoogle Scholar
  22. Grigorenko EL, Wood FB, Meyer MS, Hart LA, Speed WC, Shuster A et al (1997) Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. Am J Hum Genet 60:27–39PubMedGoogle Scholar
  23. Grigorenko EL, Wood FB, Meyer MS, Pauls JED, Hart LA, Pauls DL (2001) Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p. Am J Med Genet 105:120–129CrossRefPubMedGoogle Scholar
  24. Grigorenko EL, Ngorosho D, Jukes M, Bundy D (2006) Reading in able and disabled readers from around the word: same or different? An illustration from a study of reading-related processes in a Swahili sample of siblings. J Res Read 29:104–123CrossRefGoogle Scholar
  25. Grigorenko E, Naples A, Chang J, Romano C, Ngorosho D, Kungulilo S, Jukes M, Bundy D (2007) Back to Africa: tracing dyslexia genes in East Africa. Read Writ Interdiscip J 20:27–49CrossRefGoogle Scholar
  26. Gudbjartsson DF, Thorvaldsson T, Kong A, Gunnarsson G, Ingolfsdottir A (2005) Allegro version 2. Nat Genet 37:1015–1016CrossRefPubMedGoogle Scholar
  27. Hallgren B (1950) Specific dyslexia (“congenital word blindness”): a clinical and genetic study. Acta Psychiatr Neurol 65:2–289Google Scholar
  28. Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, Eklund R, Nopola-Hemmi J, Kääriäinen H et al (2005) The axon guidance receptorgene ROBO1 is a candidate gene for developmental dyslexia. PLoS Genet 1:467–474Google Scholar
  29. Høien T, Lundberg I (2001) Dyslexia: from theory to intervention. Kluwer Academic Publishers, Dordrecht, NLGoogle Scholar
  30. Hsiung GY, Kaplan BJ, Petryshen TL, Lu S, Field LL, Stein CM et al (2004) A dyslexia susceptibility locus (DYX7) linked to dopamine D4 receptor (DRD4) region on chromosome 11p15.5. Am J Med Genet 125:112–119CrossRefGoogle Scholar
  31. Kaplan DE, Gayán J, Ahn J, Won T-W, Pauls D, Olson RK et al (2002) Evidence for linkage and association with reading disability on 6p21.3–22. Am J Hum Genet 70:1287–1298CrossRefPubMedGoogle Scholar
  32. Lubs HA, Rabin M, Feldman E, Jallad BJ, Kushch A, Gross-Glenn K (1993) Familial dyslexia: genetic and medical findings in eleven three generation families. Ann Dyslexia 43:47–60CrossRefGoogle Scholar
  33. McGrath LM, Smith SD, Pennington BF (2006) Breakthroughs in the search for dyslexia candidate genes. Trends Mol Med 12:333–342CrossRefPubMedGoogle Scholar
  34. Meng H, Smith SD, Hager K, Held M, Liu J, Olson RK et al (2005) DCDC2 is associated with reading disability and modulates neuronal development in the brain. Natl Acad Sci 102:17053–17058CrossRefGoogle Scholar
  35. Nopola-Hemmi J, Myllyluoma B, Haltia T, Taipale M, Ollikainen V, Ahonen T et al (2001) A dominant gene for developmental dyslexia on chromosome 3. J Med Genet 38:658–664CrossRefPubMedGoogle Scholar
  36. Olson RK (2007) Introduction to the special issue on genes, environment and, reading. Read Writ 20:1–11CrossRefGoogle Scholar
  37. Olson RK, Wise B, Conners F, Rack J, Fulker D (1989) Specific deficits in component reading and language skills: genetic and environmental influences. J Learn Disabil 22, 339–348. Baltimore: BrookesGoogle Scholar
  38. Petryshen TL, Kaplan BJ, Liu MF, Field LL (2000) Absence of significant linkage between phonological coding dyslexia and chromosome 6p23–21.3, as determined by use of quantitative-trait methods: confirmation of qualitative analyses. Am J Hum Genet 66:708–714CrossRefPubMedGoogle Scholar
  39. Petryshen TL, Kaplan BJ, Liu MF, Schmill de French N, Tibias R, Hughes ML et al (2001) Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia. Am J Med Genet 105:507–517CrossRefPubMedGoogle Scholar
  40. Plomin R, Kovas Y (2005) Generalist genes and learning disabilities. Psychol Bull 131:592–617CrossRefPubMedGoogle Scholar
  41. Ramus F, Szenkovits G (2008) What phonological deficit? Q J Exp Psychol 61:129–141CrossRefGoogle Scholar
  42. Raven JC (1995) Standard progressive matrices sets A–E. Oxford Psychologists Press Ltd, OxfordGoogle Scholar
  43. Rutter M (2002) Nature, nurture, and development: from evangelism through science toward policy and practice. Child Dev 73:1–21CrossRefPubMedGoogle Scholar
  44. Scerri TS, Schulte-Körne G (2010) Genetics of developmental dyslexia. Eur Child Adolesc Psychiatry 19:179–197CrossRefPubMedGoogle Scholar
  45. Schulte-Körne G, Grimm T, Nöthen MM, Müller-Myhsok B, Cichon S, Vogt IR et al (1998) Evidence for linkage of spelling disability to chromosome 15. Am J Hum Genet 63:279–282CrossRefPubMedGoogle Scholar
  46. Schumacher J, König IR, Plume E, Propping P, Warnke A, Manthey M et al (2006) Linkage analyses of chromosomal region 18p11–q12 in dyslexia. J Neural Transm 113:417–423CrossRefPubMedGoogle Scholar
  47. Siegel LS (1999) Issues in the definition and diagnosis of learning disabilities: a perspective on Guckenberger v. Boston University. J Learn Disabil 32:304–319CrossRefPubMedGoogle Scholar
  48. Smith SD (2007) Genes, language development and language disorders. Ment Retard Dev Disabil Res Rev 13:96–105CrossRefPubMedGoogle Scholar
  49. Smith SD, Kimberling WJ, Pennington BF, Lubs HA (1983) Specific reading disability: identification of an inherited form through linkage analysis. Science 219:1345CrossRefPubMedGoogle Scholar
  50. Snowling MJ (2008) Specific disorders and broader phenotypes: the case of dyslexia. Q J Exp Psychol 61:142–156CrossRefGoogle Scholar
  51. Stanovich K, Siegel L (1994) Phenotypic performance profile of children with reading disabilities: a regression-based test of the phonological-core variable-difference model. J Educ Psychol 86:24–53CrossRefGoogle Scholar
  52. Statistics Sweden (2009). Announcement nr. 2010:102, http://www.scb.se/Pages/PressRelease_291846.aspx
  53. Svensson I (2003) Phonological dyslexia: cognitive, behavioural and hereditary aspects. Doctoral thesis, The Department of Psychology, The University of GothenburgGoogle Scholar
  54. Taipale M, Kaminen N, Nopola-Hemmi J, Haltia T, Myllyluoma B, Lyytinen H, Muller K et al (2003) A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Natl Acad Sci USA 100:11553–11558CrossRefGoogle Scholar
  55. Uppstad PH, Tønnessen FE (2007) The notion of phonology in dyslexia research: cognitivism—and beyond. Dyslexia 13:154–174CrossRefPubMedGoogle Scholar
  56. van der Leij A, de Jong PF, Rijswijk-Prins H (2001) Characteristics of dyslexia in a Dutch family. Dyslexia 7:105–124CrossRefPubMedGoogle Scholar
  57. Wadsworth SJ, Corley RP, Hewitt JK, Plomin R, DeFries JC (2002) Parent-offspring resemblance for reading performance at 7, 12 and 16 years of age in the Colorado adoption project. J Child Psychol Psychiatry 6:769–794CrossRefGoogle Scholar
  58. Wagner RW (2005) Understanding genetic and environmental influences on the development of reading: reaching for higher fruit. Sci Stud Read 9:317–326CrossRefGoogle Scholar
  59. Wigg KG, Couto JM, Feng Y, Anderson B, Cate-Carter TD, Macciardi F et al (2004) Support for EKNI as the susceptibility locus for dyslexia on 15q21. Mol Psychiatry 9:11–1121CrossRefGoogle Scholar
  60. Zhou K, Asherson P, Sham P, Franke B, Anney RJL, Buitelaar J et al (2008) Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings. Biol Psychiatry 64:571–576CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Idor Svensson
    • 1
    Email author
  • Staffan Nilsson
    • 2
  • Jan Wahlström
    • 3
  • Margareta Jernås
    • 4
  • Lena M. Carlsson
    • 4
  • Erland Hjelmquist
    • 5
  1. 1.Department of PsychologyLinnæus UniversityVäxjöSweden
  2. 2.Department of Mathematical StatisticChalmers University of TechnologyGothenburgSweden
  3. 3.Department of Clinical GeneticsSahlgrenska University Hospital/East, The University of GothenburgGothenburgSweden
  4. 4.Department of Molecular and Clinical Medicine, Sahlgrenska AcademyThe University of GothenburgGothenburgSweden
  5. 5.Department of PsychologyThe University of GothenburgGothenburgSweden

Personalised recommendations