Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Developmental dyslexia: genetic dissection of a complex cognitive trait

Nature Reviews Neuroscience volume 3, pages 767–780 (2002)Cite this article

Key Points

  • Despite decades of multidisciplinary investigation, the biological basis of dyslexia — a specific impairment of reading ability — remains obscure. But a series of recent studies has emphasized the contribution of genetic factors to this disorder.

  • Dyslexia runs in families, and studies of monozygotic and dizygotic twins have provided valuable insights into the heritability of the condition. Methods developed for these studies have also aided in the genetic mapping of this reading disability.

  • For several reasons, the genetic analysis of dyslexia is complex. For example, there is no straightforward correspondence between genotype and phenotype, and phenotypic variations can depend on the developmental stage of the subject. Similarly, there is a lack of consensus on the definition of dyslexia, and on whether it is a single trait or a cluster of traits with distinct aetiologies.

  • Successful localization of genes that influence dyslexia has been aided by innovations in three areas. First, methods have been developed for mapping genes that contribute to quantitative variability in reading performance. Second, researchers are dissecting the phenotypic profile into distinct but related components for genetic study. Third, it is now possible to scan all chromosomes of the genome when searching for genes that influence complex traits such as dyslexia.

  • Targeted linkage studies of dyslexia have provided strong evidence that two chromosomal regions — 15q21 and 6p21 — are involved in this syndrome. Similarly, genome-wide scans have identified further regions on chromosomes 2, 3 and 18 that seem to be linked to dyslexia in multiple independent sets of families.

  • Although the linkage results highlight chromosomal regions that are involved in dyslexia susceptibility, finding individual genes that are affected remains a daunting task. So far, no specific dyslexia gene has been identified, but studies of speech and language deficits have found a gene — FOXP2 — that is responsible for a rare form of the disorder.

Abstract

Developmental dyslexia, a specific impairment of reading ability despite adequate intelligence and educational opportunity, is one of the most frequent childhood disorders. Since the first documented cases at the beginning of the last century, it has become increasingly apparent that the reading problems of people with dyslexia form part of a heritable neurobiological syndrome. As for most cognitive and behavioural traits, phenotypic definition is fraught with difficulties and the genetic basis is complex, making the isolation of genetic risk factors a formidable challenge. Against such a background, it is notable that several recent studies have reported the localization of genes that influence dyslexia and other language-related traits. These investigations exploit novel research approaches that are relevant to many areas of human neurogenetics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: IBD allele sharing can be assessed using polymorphic genetic markers.
Figure 2: Methods for QTL-based linkage mapping in humans.
Figure 3: Replicated regions of chromosomes 2, 3, 6, 15 and 18 implicated by linkage studies of dyslexia.
Figure 4: Genetic dissection of dyslexia.

Similar content being viewed by others

References

  1. Hinshelwood, J. Word blindness and visual memories. Lancet 2, 1566–1570 (1895).

    Google Scholar 

  2. Morgan, W. P. A case of congenital word blindness. Br. Med. J. 2, 1378 (1896).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Orton, S. T. Word-blindness in school children. Arch. Neurol. Psychiatr. 14, 582–615 (1925).

    Article  Google Scholar 

  4. Snowling, M. J. From language to reading and dyslexia. Dyslexia 7, 37–46 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Wolf, M. & Bowers, P. G. Naming-speed processes and developmental reading disabilities: an introduction to the special issue on the double-deficit hypothesis. J. Learn. Disabil. 33, 322–324 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Eden, G. F. et al. Abnormal processing of visual motion in dyslexia revealed by functional brain imaging. Nature 382, 66–69 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Temple, E. et al. Disruption of the neural response to rapid acoustic stimuli in dyslexia: evidence from functional MRI. Proc. Natl Acad. Sci. USA 97, 13907–13912 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nicolson, R. I., Fawcett, A. J. & Dean, P. Developmental dyslexia: the cerebellar deficit hypothesis. Trends Neurosci. 24, 508–511 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Stein, J. & Walsh, V. To see but not to read; the magnocellular theory of dyslexia. Trends Neurosci. 20, 147–152 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Hari, R. & Renvall, H. Impaired processing of rapid stimulus sequences in dyslexia. Trends Cogn. Sci. 5, 525–532 (2001).

    Article  PubMed  Google Scholar 

  11. Habib, M. The neurological basis of developmental dyslexia. An overview and working hypothesis. Brain 123, 2373–2399 (2000).A comprehensive discussion of multidisciplinary investigations into the aetiology of dyslexia.

    Article  PubMed  Google Scholar 

  12. Thomas, C. J. Congenital 'word-blindness' and its treatment. Ophthalmoscope 3, 380–385 (1905).

    Google Scholar 

  13. Stephenson, S. Six cases of congenital word-blindness affecting three generations of one family. Ophthalmoscope 5, 482–484 (1907).

    Google Scholar 

  14. Hallgren, B. Specific dyslexia ('congenital word blindness'): a clinical and genetic study. Acta Psychiatr. Neurol. Scand. 65 (Suppl.), 1–287 (1950).

    CAS  Google Scholar 

  15. Finucci, J. M., Guthrie, J. T., Childs, A. L., Abbey, H. & Childs, B. The genetics of specific reading disability. Ann. Hum. Genet. 40, 1–23 (1976).

    Article  CAS  PubMed  Google Scholar 

  16. Lewitter, F. I., DeFries, J. C. & Elston, R. C. Genetic models of reading disabilities. Behav. Genet. 10, 9–30 (1980).

    Article  CAS  PubMed  Google Scholar 

  17. Vogler, G. P., DeFries, J. C. & Decker, S. N. Family history as an indicator of risk for reading disability. J. Learn. Disabil. 18, 419–421 (1985).

    Article  CAS  PubMed  Google Scholar 

  18. Pennington, B. F. et al. Evidence for major gene transmission of developmental dyslexia. JAMA 266, 1527–1534 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Wolff, P. H. & Melngailis, I. Family patterns of developmental dyslexia: clinical findings. Am. J. Med. Genet. 54, 122–131 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Bakwin, H. Reading disability in twins. Dev. Med. Child Neurol. 15, 184–187 (1973).

    Article  CAS  PubMed  Google Scholar 

  21. Stevenson, J., Graham, P., Fredman, G. & McLoughlin, V. A twin study of genetic influences on reading and spelling ability and disability. J. Child Psychol. Psychiatry 28, 229–247 (1987).

    Article  CAS  PubMed  Google Scholar 

  22. DeFries, J. C., Fulker, D. W. & LaBuda, M. C. Evidence for a genetic aetiology in reading disability of twins. Nature 329, 537–539 (1987).

    Article  CAS  PubMed  Google Scholar 

  23. DeFries, J. C. & Alarcón, M. Genetics of specific reading disability. Ment. Retard. Dev. Disabil. Res. Rev. 2, 39–47 (1996).

    Article  Google Scholar 

  24. Pennington, B. F. & Lefly, D. L. Early reading development in children at family risk for dyslexia. Child Dev. 72, 816–833 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. DeFries, J. C. & Fulker, D. W. Multiple regression analysis of twin data. Behav. Genet. 15, 467–473 (1985).

    Article  CAS  PubMed  Google Scholar 

  26. DeFries, J. C. & Gillis, J. J. in Nature, Nurture, and Psychology (eds Plomin, R. & McClearn, G.) 121–145 (American Psychiatric Association, Washington DC, 1993).

    Book  Google Scholar 

  27. Gayán, J. & Olson, R. K. Genetic and environmental influences on orthographic and phonological skills in children with reading disabilities. Dev. Neuropsychol. 20, 483–507 (2001).

    Article  PubMed  Google Scholar 

  28. Bishop, D. V. M. et al. Different origin of auditory and phonological processing problems in children with language impairment: evidence from a twin study. J. Speech Lang. Hear. Res. 42, 155–168 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Stevenson, J. Evidence for a genetic etiology in hyperactivity in children. Behav. Genet. 22, 337–344 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Fisher, S. E. & Smith, S. D. in Dyslexia: Theory and Good Practice (ed. Fawcett, A. J.) 39–64 (Whurr, London, UK, 2001).

    Google Scholar 

  31. Fisher, S. E. in Behavioral Genetics in the Postgenomic Era (eds Plomin, R., DeFries, J. C., Craig, I. W. & McGuffin, P.) 205–226 (American Psychiatric Association, Washington DC, 2002).

    Google Scholar 

  32. Smith, S. D., Kimberling, W. J., Pennington, B. F. & Lubs, H. A. Specific reading disability: identification of an inherited form through linkage analysis. Science 219, 1345 (1983).

    Article  CAS  PubMed  Google Scholar 

  33. Cardon, L. R. et al. Quantitative trait locus for reading disability on chromosome 6. Science 266, 276–279 (1994).An early demonstration of the value of applying QTL mapping methods to continuous measures of cognitive ability. Strong evidence was provided for a locus on 6p, which was subsequently verified in several independent populations.

    Article  CAS  PubMed  Google Scholar 

  34. Cardon, L. R. et al. Quantitative trait locus for reading disability: correction. Science 268, 1553 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. Grigorenko, E. L. et al. Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. Am. J. Hum. Genet. 60, 27–39 (1997).This paper proposed the intriguing idea that differing aspects of the dyslexia profile might link to distinct genetic loci. Although some conclusions from this study have been criticized, it raised the key question of whether we can reliably dissect complex cognitive phenotypes using genetic linkage data.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Field, L. L. & Kaplan, B. J. Absence of linkage of phonological coding dyslexia to chromosome 6p23–p21.3 in a large family data set. Am. J. Hum. Genet. 63, 1448–1456 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fisher, S. E. et al. A quantitative trait locus on chromosome 6p influences different aspects of developmental dyslexia. Am. J. Hum. Genet. 64, 146–156 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bisgaard, M. L., Eiberg, H., Moller, N., Niebuhr, E. & Mohr, J. Dyslexia and chromosome 15 heteromorphism: negative lod score in a Danish sample. Clin. Genet. 32, 118–119 (1987).

    Article  CAS  PubMed  Google Scholar 

  39. Froster, U., Schulte-Körne, G., Hebebrand, J. & Remschmidt, H. Cosegregation of balanced translocation (1;2) with retarded speech development and dyslexia. Lancet 342, 178–179 (1993).

    Article  CAS  PubMed  Google Scholar 

  40. Schulte-Körne, G. et al. Evidence for linkage of spelling disability to chromosome 15. Am. J. Hum. Genet. 63, 279–282 (1998).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Fagerheim, T. et al. A new gene (DYX3) for dyslexia is located on chromosome 2. J. Med. Genet. 36, 664–669 (1999).The successful genome-wide application of traditional parametric methods led to the localization of a dyslexia risk gene in a single large pedigree.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Nopola-Hemmi, J. et al. A dominant gene for developmental dyslexia on chromosome 3. J. Med. Genet. 38, 658–664 (2001).A genome-wide study of a large extended family identified a susceptibility locus for dyslexia on chromosome 3. References 41 and 42 provide a clear example of genetic heterogeneity, even when investigating multigenerational pedigrees.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Castles, A. & Coltheart, M. Varieties of developmental dyslexia. Cognition 47, 149–180 (1993).

    Article  CAS  PubMed  Google Scholar 

  44. Castles, A., Datta, H., Gayán, J. & Olson, R. K. Varieties of developmental reading disorder: genetic and environmental influences. J. Exp. Child Psychol. 72, 73–94 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. Lander, E. S. & Schork, N. J. Genetic dissection of complex traits. Science 265, 2037–2048 (1994).An excellent introduction to key concepts of complex genetic analysis.

    Article  CAS  PubMed  Google Scholar 

  46. Haseman, J. K. & Elston, R. C. The investigation of linkage between a quantitative trait and a marker locus. Behav. Genet. 2, 3–19 (1972).

    Article  CAS  PubMed  Google Scholar 

  47. Cardon, L. R. & Fulker, D. W. The power of interval mapping of quantitative trait loci, using selected sib pairs. Am. J. Hum. Genet. 55, 825–833 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Amos, C. I. Robust variance-components approach for assessing genetic linkage in pedigrees. Am. J. Hum. Genet. 54, 535–543 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Allison, D. B. et al. Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure. Am. J. Hum. Genet. 65, 531–544 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fisher, S. E. et al. Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nature Genet. 30, 86–91 (2002).This paper reported the first QTL-based genome-wide linkage scans for dyslexia, yielding robust evidence for a chromosome 18 locus influencing dyslexia in three independent samples of sib-pairs, and implicating a number of other potential loci of interest.

    Article  CAS  PubMed  Google Scholar 

  51. Gayán, J. et al. Quantitative trait locus for specific language and reading deficits on chromosome 6p. Am. J. Hum. Genet. 64, 157–164 (1999).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Davis, C. J. et al. Etiology of reading difficulties and rapid naming: the Colorado Twin Study of Reading Disability. Behav. Genet. 31, 625–635 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Wijsman, E. M. et al. Segregation analysis of phenotypic components of learning disabilities. I. Nonword memory and digit span. Am. J. Hum. Genet. 67, 631–646 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Raskind, W. H., Hsu, L., Berninger, V. W., Thomson, J. B. & Wijsman, E. M. Familial aggregation of dyslexia phenotypes. Behav. Genet. 30, 385–396 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Marlow, A. J. et al. Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK. Behav. Genet. 31, 219–230 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Fisher, S. E., Stein, J. F. & Monaco, A. P. A genome-wide search strategy for identifying quantitative trait loci involved in reading and spelling disability (developmental dyslexia). Eur. Child Adolesc. Psychiatry 8 (Suppl. 3), 47–51 (1999).

    Article  PubMed  Google Scholar 

  57. Kruglyak, L. & Lander, E. S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439–454 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembrey, M. E. Localisation of a gene implicated in a severe speech and language disorder. Nature Genet. 18, 168–170 (1998).

    Article  CAS  PubMed  Google Scholar 

  59. The SLI consortium. A genomewide scan identifies two novel loci involved in specific language impairment. Am. J. Hum. Genet. 70, 384–398 (2002).

  60. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).A technical overview of central concerns in the sound interpretation of linkage data when analysing complex traits.

    Article  CAS  PubMed  Google Scholar 

  61. Altmüller, J., Palmer, L. J., Fischer, G., Scherb, H. & Wjst, M. Genomewide scans of complex human diseases: true linkage is hard to find. Am. J. Hum. Genet. 69, 936–950 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rabin, M. et al. Suggestive linkage of developmental dyslexia to chromosome 1p34–p36. Lancet 342, 178 (1993).

    Article  CAS  PubMed  Google Scholar 

  63. Smith, S. D., Kimberling, W. J. & Pennington, B. F. Screening for multiple genes influencing dyslexia. Read. Writ. 3, 285–298 (1991).

    Article  Google Scholar 

  64. Fulker, D. W. et al. Multiple regression of sib-pair data on reading to detect quantitative trait loci. Read. Writ. 3, 299–313 (1991).

    Article  Google Scholar 

  65. Grigorenko, E. L., Wood, F. B., Meyer, M. S. & Pauls, D. L. Chromosome 6p influences on different dyslexia-related cognitive processes: further confirmation. Am. J. Hum. Genet. 66, 715–723 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Geschwind, N. & Behan, P. Left-handedness: association with immune disease, migraine, and developmental learning disorder. Proc. Natl Acad. Sci. USA 79, 5097–5100 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gilger, J. W. et al. A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data. Brain Cogn. 36, 310–333 (1998).

    Article  CAS  PubMed  Google Scholar 

  68. Petryshen, T. L., Kaplan, B. J., Liu, M. F. & Field, L. L. 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, 708–714 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Grigorenko E. L. et al. Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p. Am. J. Med. Genet. 105, 120–129 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Petryshen T. L. et al. Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia. Am. J. Med. Genet. 105, 507–517 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Francks, C. et al. Quantitative association analysis within the chromosome 2p12–16 dyslexia susceptibility region: microsatellite markers and candidate genes SEMA4F and OTX1. Psychiatr. Genet. 12, 35–41 (2002).

    Article  PubMed  Google Scholar 

  72. Petryshen, T. L., Kaplan, B. J., Hughes, M. L., Tzenova, J. & Field, L. L. Supportive evidence for the DYX3 dyslexia susceptibility gene in Canadian families. J. Med. Genet. 39, 125–126 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Nopola-Hemmi, J. et al. Two translocations of chromosome 15q associated with dyslexia. J. Med. Genet. 37, 771–775 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cardon, L. R. & Bell, J. I. Association study designs for complex diseases. Nature Rev. Genet. 2, 91–99 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Morris, D. W. et al. Family-based association mapping provides evidence for a gene for reading disability on chromosome 15q. Hum. Mol. Genet. 9, 843–848 (2000).Converging evidence for a locus on 15q has been revealed by complementary approaches to linkage mapping, including this report of association and a study of chromosomal abnormalities (reference 73).

    Article  CAS  PubMed  Google Scholar 

  76. Kaplan, D. E. et al. Evidence for linkage and association with reading disability on 6p21.3–22. Am. J. Hum. Genet. 70, 1287–1298 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pennington, B. F. Using genetics to dissect cognition. Am. J. Hum. Genet. 60, 13–16 (1997).An insightful critique of the suggestion that genes might show simple mapping to individual cognitive processes that underlie dyslexia.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Goring, H. H., Terwilliger, J. D. & Blangero, J. Large upward bias in estimation of locus-specific effects from genomewide scans. Am. J. Hum. Genet. 69, 1357–1369 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Willcutt, E. G. et al. Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/hyperactivity disorder. Am. J. Med. Genet. 114, 260–268 (2002).

    Article  PubMed  Google Scholar 

  80. Lai, C. S. L. et al. The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. Am. J. Hum. Genet. 67, 357–368 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lai, C. S. L., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. & Monaco, A. P. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001).This paper reports the identification of the FOXP2 gene and shows that its disruption causes one form of speech and language impairment. This is the only known case of a direct link between a specific gene and this type of developmental disorder.

    Article  CAS  PubMed  Google Scholar 

  82. Newbury, D. F. et al. FOXP2 is not a major susceptibility gene for autism or Specific Language Impairment (SLI). Am. J. Hum. Genet. 70, 1318–1327 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Nokelainen, P. & Flint, J. Genetic effects on human cognition: lessons from the study of mental retardation syndromes. J. Neurol. Neurosurg. Psychiatry 72, 287–296 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Thomson, M. E. The assessment of children with specific reading disabilities (dyslexia) using the British Ability Scales. Br. J. Psychol. 73, 461–478 (1982).

    Article  CAS  PubMed  Google Scholar 

  85. Siegel, L. S. & Himel, N. Socioeconomic status, age and the classification of dyslexics and poor readers: the dangers of using IQ scores in the definition of reading disability. Dyslexia 4, 90–103 (1998).

    Article  Google Scholar 

  86. Pennington, B. F., Gilger, J. W., Olson, R. K. & DeFries, J. C. The external validity of age- versus IQ-discrepancy definitions of reading disability: lessons from a twin study. J. Learn. Disabil. 25, 562–573 (1992).

    Article  CAS  PubMed  Google Scholar 

  87. Shapiro, B. K. Specific reading disability: a multiplanar view. Ment. Retard. Dev. Disabil. Res. Rev. 7, 13–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Shaywitz, S. E. et al. Persistence of dyslexia: the Connecticut Longitudinal Study at adolescence. Pediatrics 104, 1351–1359 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Nehls, M., Pfeifer, D., Schorpp, M., Hedrich, H. & Boehm, T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372, 103–107 (1994).

    Article  CAS  PubMed  Google Scholar 

  90. Nishimura, D. Y. et al. The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nature Genet. 19, 140–147 (1998).

    Article  CAS  PubMed  Google Scholar 

  91. Fang, J. et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema–distichiasis syndrome. Am. J. Hum. Genet. 67, 1382–1388 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Brunkow, M. E. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nature Genet. 27, 68–73 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Crisponi, L. et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nature Genet. 27, 159–166 (2001).

    Article  CAS  PubMed  Google Scholar 

  94. Hurst, J. A., Baraitser, M., Auger, E., Graham, F. & Norell, S. An extended family with a dominantly inherited speech disorder. Dev. Med. Child Neurol. 32, 347–355 (1990).

    Google Scholar 

  95. Vargha-Khadem, F., Watkins, K., Alcock, K., Fletcher, P. & Passingham, R. Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proc. Natl Acad. Sci. USA 92, 930–933 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Bishop, D. V. M. Putting language genes in perspective. Trends Genet. 18, 57–59 (2002).An interesting discussion of what the discovery of FOXP2 might tell us about speech and language development.

    Article  CAS  PubMed  Google Scholar 

  97. Fisher S. E. in Neurosciences at the Postgenomic Era (eds Mallet, J. & Christen, Y.) (Springer–Verlag, Heidelberg, Germany, 2002).

    Google Scholar 

Download references

Acknowledgements

S.E.F. is a Royal Society Research Fellow. J.C.D. is supported by a centre grant from the National Institute of Child Health and Human Development.

Author information

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Simon E. Fisher

  2. Institute for Behavioral Genetics, University of Colorado, Boulder, 80309-0447, Colorado, USA

    John C. DeFries

Authors
  1. Simon E. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John C. DeFries
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon E. Fisher.

Related links

Related links

DATABASES

LocusLink

FOXP2

OMIM

ADHD

dyslexia

OMIM Gene Map

1p22

1p34–36

2p15–16

2q31

3p12–q13

6p21.3

6q12

15q21

18p11.2

FURTHER INFORMATION

Encyclopedia of Life Sciences

language

quantitative genetics

MIT Encyclopedia of Cognitive Sciences

dyslexia

language impairment, developmental

reading

visual word recognition

Wellcome Trust Centre for Human Genetics

FOXP2 in Speech and Language Disorder

Genetics of Developmental Dyslexia

Genetics of Specific Language Impairment

Glossary

PHONEMES

Individual units of speech sound that combine to make words.

MENDELIAN

A trait resulting from changes in a single gene that has a significant effect on the phenotype and is inherited in a simple pattern that is similar or identical to those described by Gregor Mendel. Also referred to as monogenic.

PROBAND

Usually, the person who serves as the starting point of a genetic study.

MONOZYGOTIC

Twins that develop from a single fertilized egg cell through its division into two genetically identical parts.

DIZYGOTIC

Twins that develop during the same pregnancy as the result of two separate eggs being fertilized by two separate sperm.

HERITABILITY

The proportion of variability in a particular characteristic that can be attributed to genetic influences. This is a statistical description that applies to a specific population and might change if the environment is altered.

SPECIFIC LANGUAGE IMPAIRMENT

A significant deficit in language development in children with normal non-verbal intelligence that cannot be attributed to hearing loss, inadequate educational opportunity or obvious neurological impairment.

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

A common disorder with childhood onset, in which persistent inattention and/or hyperactive–impulsive behaviour leads to impaired social and/or academic functioning.

CANDIDATE GENE

A gene that encodes a protein, the expected or known function of which indicates that it might be responsible for a disease or trait in a population of individuals. Pure candidate-gene approaches do not exploit or require information on chromosomal location (in contrast to 'positional cloning').

POLYMORPHIC GENETIC MARKERS

Naturally occurring variants in DNA sequence that can be used to track the inheritance pattern of a particular chromosomal location.

POSITIONAL CLONING

A strategy for the identification of disease genes on the basis of marker inheritance data from affected families that does not require any prior knowledge of the underlying biological pathways or gene function (in contrast to 'candidate-gene' approaches). In recent years, a blend of positional cloning and candidate-gene approaches (sometimes referred to as a 'positional-candidate' strategy) has often been used, involving the combined use of data on map location and expected gene function.

GENOTYPE

The genetic constitution of an individual. This can refer to the entire complement of genetic material or to a specific gene (or set of genes).

PHENOTYPE

The appearance of an individual in terms of a particular characteristic (physical, biochemical, physiological and so on), resulting from interactions between the individual's genotype and the environment.

PENETRANCE

The probability that an individual with a particular genotype manifests a given phenotype. Complete penetrance corresponds to the situation in which every individual with the same specific genotype manifests the phenotype in question.

PHENOCOPIES

People who manifest the same phenotype as other individuals of a particular genotype, but do not possess this genotype themselves. For example, this might occur when environmental influences alone evoke a developmental trait that has a similar genetic counterpart.

OLIGOGENICITY

When a few different genes work together to contribute to a particular phenotype.

POWER

The probability of correctly rejecting the null hypothesis when it is truly false. For linkage studies, the null hypothesis is that of 'no linkage', so the power represents the probability of correctly detecting a genuine linkage.

QUANTITATIVE TRAIT LOCUS

(QTL). A genetic locus or chromosomal region that contributes to variability in a complex quantitative trait (such as body weight), as identified by statistical analysis.

POLYGENIC

The effects of a large number of different genes, each of which has a slight influence on the phenotypic outcome.

GRAPHEME

A written symbol, or group of symbols, that is used to represent a specific phoneme.

MULTIPOINT ANALYSIS

The use of data obtained from multiple neighbouring genetic markers on the same chromosome to extract linkage information at many points across a genomic region.

SINGLE-POINT ANALYSIS

The investigation of linkage at one point on a chromosome, using data from a single marker.

LOD SCORE

Linkage mapping involves comparing two likelihoods. The first is the likelihood of the data, under the hypothesis that there is linkage between inheritance of the trait and that of the chromosomal region in question. The second is the likelihood of the data, under the null hypothesis that there is no linkage. The lod score is the logarithm of the likelihood ratio; if it exceeds a given threshold, the null hypothesis can be rejected.

CHROMOSOMAL HETEROMORPHISM

Natural variation in the shape or staining pattern of a chromosome, as viewed under the microscope.

CENTROMERE

The constricted region of a chromosome that includes the site of attachment to the mitotic or meiotic spindle. Geneticists divide the chromosome into 'short' and 'long' arms, which are separated by this centromere.

CENTIMORGAN

A standard measure of genetic distance that is derived from observations of recombination between neighbouring loci. The relationship to actual physical distance along a chromosome varies throughout the genome; on average, 1 centimorgan corresponds to around one million bases of DNA.

HLA COMPLEX

A well-studied region of chromosome 6p that contains many loci, such as the human leukocyte antigen (HLA) genes, which encode key components of the immune system. Also known as the major histocompatibility complex (MHC).

AUTOSOMAL DOMINANT

One type of inheritance pattern that is observed for monogenic traits. Autosomes are any chromosomes in a cell that are not sex chromosomes. Autosomal dominant transmission results when an abnormal copy of an autosomal gene from a single parent gives rise to the trait, even though the copy inherited from the other parent is normal.

TRANSLOCATION

A genetic rearrangement in which part of a chromosome is detached by breakage and becomes attached to another part of the same chromosome, or to a different chromosome.

DUPLICATION

A genetic rearrangement that involves the doubling or repetition of part of a chromosome.

DELETION

A genetic rearrangement that involves the loss of part of a chromosome.

INVERSION

A genetic rearrangement in which part of a chromosome is reversed, so that the genes within that part are in inverse order.

BREAKPOINT

The specific site of chromosomal breakage that is associated with a particular chromosomal rearrangement.

LINKAGE DISEQUILIBRIUM

Non-random association between specific allelic variants at one genetic locus and those at another genetic locus that maps nearby.

EFFECT SIZE

A standardized measure of effect that is adopted when different scales are used to measure an outcome. In QTL analyses, the effect size is the proportion of variability in a measure that is attributable to the genetic locus of interest.

TRANSCRIPTION FACTOR

A DNA-binding protein that regulates gene expression.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fisher, S., DeFries, J. Developmental dyslexia: genetic dissection of a complex cognitive trait. Nat Rev Neurosci 3, 767–780 (2002). https://doi.org/10.1038/nrn936

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn936

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing