Genetics of developmental dyslexia (original) (raw)
Related papers
Neuroscience, 2013
Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA + KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid-to lategestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia. Ó
Identification of novel dyslexia candidate genes through the analysis of a chromosomal deletion
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2009
Dyslexia is the most common childhood learning disorder and it is a significantly heritable trait. At least nine chromosomal loci have been linked to dyslexia, and additional susceptibility loci on other chromosomes have been suggested. Within two of these loci, DYX1C1 (15q21) and ROBO1 (3p12) have recently been proposed as dyslexia candidate genes through the molecular analysis of translocation breakpoints in dyslexic individuals carrying balanced chromosomal translocations. Moreover, genetic association studies have indicated a cluster of five dyslexia candidate genes in another linkage region on chromosome 6p22, although there is currently no consensus about which of these five genes contributes to the genetic susceptibility for dyslexia. In this article, we report the identification of four new dyslexia candidate genes (PCNT, DIP2A, S100B, and PRMT2) on chromosome region 21q22.3 by FISH and SNP microarray analyses of a very small deletion in this region, which cosegregates with dyslexia in a father and his three sons.
The Lancet Neurology, 2002
Dyslexia, a disorder of reading and spelling, is a heterogeneous neurological syndrome with a complex genetic and environmental aetiology. People with dyslexia differ in their individual profiles across a range of cognitive, physiological, and behavioural measures related to reading disability. Some or all of the subtypes of dyslexia might have partly or wholly distinct genetic causes. An understanding of the role of genetics in dyslexia could help to diagnose and treat susceptible children more effectively and rapidly than is currently possible and in ways that account for their individual disabilities. This knowledge will also give new insights into the neurobiology of reading and language cognition. Genetic linkage analysis has identified regions of the genome that might harbour inherited variants that cause reading disability. In particular, loci on chromosomes 6 and 18 have shown strong and replicable effects on reading abilities. These genomic regions contain tens or hundreds of candidate genes, and studies aimed at the identification of the specific causal genetic variants are underway.
A new gene (DYX3) for dyslexia is located on chromosome 2
Journal of medical genetics, 1999
Developmental dyslexia is a specific reading disability affecting children and adults who otherwise possess normal intelligence, cognitive skills, and adequate schooling. Difficulties in spelling and reading may persist through adult life. Possible localisations of genes for dyslexia have been reported on chromosomes 15 (DYX1), 6p21.3-23 (DYX2), and 1p over the last 15 years. Only the localisation to 6p21.3-23 has been clearly confirmed and a genome search has not previously been carried out. We have investigated a large Norwegian family in which dyslexia is inherited as an autosomal dominant trait. A genome wide search for linkage with an average 20 cM marker density was initiated in 36 of the 80 family members. The linkage analysis was performed under three different diagnostic models. Linkage analysis in the family identified a region in 2p15-p16 which cosegregated with dyslexia. Maximum lod scores of 3.54, 2.92, and 4.32 for the three different diagnostic models were obtained. T...
Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18
PLoS ONE, 2010
Background: Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis.
Discovery of 42 Genome-Wide Significant Loci Associated with Dyslexia
2021
ABSTRACTReading and writing are crucial for many aspects of modern life but up to 1 in 10 children are affected by dyslexia [1, 2], which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70% [3, 4], yet no convincing genetic markers have been found due to limited study power [5]. Here, we present a genome-wide association study representing a 20-fold increase in sample size from prior work, with 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls. We identified 42 independent genome-wide significant loci: 17 are in genes linked to or pleiotropic with cognitive ability/educational attainment; 25 are novel and may be more specifically associated with dyslexia. Twenty-three loci (12 novel) were validated in independent cohorts of Chinese and European ancestry. We confirmed a similar genetic aetiology of dyslexia between sexes, and found genetic covariance with many traits, including ambidexterity, but not neuroanatomical measures of...
Two translocations of chromosome 15q associated with dyslexia
Journal of Medical Genetics, 2000
Developmental dyslexia is characterised by diYculties in learning to read. As reading is a complex cognitive process, multiple genes are expected to contribute to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of molecular studies during recent years, but so far no genes have been identified. However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in previous linkage studies. We have identified two families with balanced translocations involving the 15q21-q22 region. In one family, the translocation segregates with specific dyslexia in three family members. In the other family, the translocation is associated with dyslexia in one family member. We have performed fluorescence in situ hybridisation (FISH) studies to refine the position of the putative dyslexia locus further. Our results indicate that both translocation breakpoints on 15q map within an interval of approximately 6-8 Mb between markers D15S143 and D15S1029, further supporting the presence of a locus for specific dyslexia on 15q21. (J Med Genet 2000;37:771-775)
Linkage analyses of chromosomal region 18p11-q12 in dyslexia
Journal of Neural Transmission, 2006
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
The genetic lexicon of dyslexia
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2007
Reading abilities are acquired only through specific teaching and training. A significant proportion of children fail to achieve these skills despite normal intellectual abilities and an appropriate opportunity to learn. Difficulty in learning to read is attributable to specific dysfunctions of the brain, which so far remain poorly understood. However, it is recognized that the neurological basis for dyslexia, or reading disability, is caused in large part by genetic factors. Linkage studies have successfully identified several regions of the human genome that are likely to harbor susceptibility genes for dyslexia. In the past few years there have been exciting advances with the identification of four candidate genes located within three of these linked chromosome regions: DYX1C1 on chromosome 15, ROBO1 on chromosome 3, and KIAA0319 and DCDC2 on chromosome 6. Functional studies of these genes are offering new insights about the biological mechanisms underlying the development of dyslexia and, in general, of cognition.