Data for this review were identified by searches of PubMed and references from relevant articles; articles were also identified through searches of the files of the authors. The search terms “dyslexia” and “reading disability” were used. Only papers written in English were reviewed.
ReviewThe genetic basis of dyslexia
Section snippets
Biology of reading
Reading is a complex multicomponent process both physiologically2 and cognitively.8, 12 In brief outline, reading must begin with sensing of visual stimuli and processing of information through the pathway of retina, lateral geniculate nuclei, and primary visual cortex.13 At some stage, visual information is probably made available to neuronal systems that apply learned, language-specific rules to convert symbolic images into component representations of language.14 In this form, the
Cognitive aspects of reading
Researchers typically attempt to dissect the cognition of reading into conceptually distinct component skills. The close relation between reading and language lies at the heart of many efforts to identify cognitive deficits involved in dyslexia. In particular, the form in which deconstructed language is processed has provided the main focus for cognitive models of reading disability.27 In this regard, dyslexia research overlaps with research into specific language impairment (SLI), a closely
Development
In cognitive terms, single-word reading is sometimes described as a multicomponent process, intermediate in a nested hierarchy of processes that range from basic phoneme processing to the overall comprehension of extended text. As such, single-word-reading ability has been described as a broad and definitive indicator of reading skill,34 with population variance in some of the other component skills thought to account for the overall variance within single-word-reading measures.8
However,
Genetic epidemiology
A genetic involvement in dyslexia has long been evident from studies showing familial clustering of the disorder1, 3, 38 and more recently through twin studies.6, 7, 8, 9, 12 In twin studies, monozygotic twins will be, on average, more similar for measures that are heritable than dizygotic twins, since monozygotic pairs share all of their segregating alleles identical-by-descent from their parents, as opposed to dizygotic twins who share, on average, half.46 Environmental effects are assumed to
Genetic dissection
Do different cognitive processes involved in reading develop independently of one another to some degree? If so, the existence of different genetic subtypes of dyslexia might be identified through epidemiological and gene mapping studies. In a pioneering study, Olson and colleagues8 used a modification of Defries-Fulker regression (figure 1) on their Colorado twin data, in which probands were selected on one cognitive variable and co-twin regression was assessed on a different but correlated
Gene mapping
Recent advances in high-throughput molecular genetic techniques and statistical methods have made possible several large-scale studies aimed at identification and mapping of the genetic variants that underlie individual differences in reading ability.10, 11 The identification of these genetic variants will allow more sophisticated analyses of the links between different reading-related cognitive, physiological, and behavioural measures than has been possible, which could lead to the
Studies so far
For the reasons described above, dyslexia researchers have tended to use linkage analysis in the first instance to identify broad genomic regions that contain tens or hundreds of potential candidate genes,11 and association analysis is used within these defined regions. Various linkage studies have been done, and many regions of the genome that might harbour genetic variants that predispose to dyslexia have been identified.10, 11, 34, 35, 36, 37, 44, 45, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,
Conclusion
One aim of molecular genetic research into dyslexia is to provide a better understanding of the specific problems that affect individual children with dyslexia, since there are subtypes of dyslexia that may be influenced by partly distinct genetic factors. Linkage mapping studies, the first of which have now been completed, are the first steps towards a molecular genetic dissection of dyslexia.78 Genetic association studies are now under way,58, 79, 80 targeted within the genomic regions
Search strategy and selection criteria
GLOSSARY
- Phonological awareness
- Ability to reflect explicitly on, and manipulate, the units of spoken language.
- Phonological decoding
- Parsing written text into phonetic units, usually measured by reading of nonsense words (eg, tegwop).
- Orthographic coding
- Reading words by recognising their holistic form, usually measured by reading irregular words that violate standard letter-sound conventions (eg, yacht).
- Word recognition or single-word reading
- Reading of single real words of various types and difficulties as
References (80)
- et al.
Varieties of developmental dyslexia
Cognition
(1993) How infants begin to extract words from speech
Trends Cogn Sci
(1999)Brain mechanisms in normal and dyslexic readers
Curr Opin Neurobiol
(2002)- et al.
Neural systems affected in developmental dyslexia revealed by functional neuroimaging
Neuron
(1998) - et al.
Developmental dyslexia: the cerebellar deficit hypothesis
Trends Neurosci
(2001) - et al.
Cerebellar morphology in developmental dyslexia
Neuropsychologia
(2002) - et al.
Interhemispheric sensorimotor integration in pointing movements: a study on dyslexic adults
Neuropsychologia
(2002) - et al.
To see but not to read: the magnocellular theory of dyslexia
Trends Neurosci
(1997) - et al.
Chromosome 6p influences on different dyslexiarelated cognitive processes: further confirmation
Am J Hum Genet
(2000) - et al.
A quantitative trait locus on chromosome 6p influences different aspects of developmental dyslexia
Am J Hum Genet
(1999)