![Figure 3. The ROBO1 (roundabout, axon guidance receptor, homolog 1) gene. An ideogram of chromosome 3 is shown at the top, with ‘p’ and ‘q’ arms indicated. The red bar shows the DYX5 region, corresponding to cytogenetic bands 3p12-q13, which was identified by linkage analyses of one large multigeneration family with apparent dominant inheritance of dyslexia [50]. The genomic organisation of the ROBO1 gene (also known as DUTT1) in 3p12.3 is shown in the bottom half of the figure. Boxes indicate exons (included in the mature transcript), lines indicate introns (removed by splicing), and the arrow shows the direction of transcription. Differences in shading of boxes relate to alternative splicing of this gene, which generates several distinct products, probably with diverse functions. Purple shading shows the intronic region disrupted by a translocation breakpoint in an individual with dyslexia (unrelated to the large DYX5-linked family) [16]. Part of this figure is adapted from [16].](/figures/figure-3-the-robo1-roundabout-axon-guidance-receptor-homolog-2z205je0.webp)
![Figure 1. The DYX1C1 gene. An ideogram of chromosome 15 is shown at the top, illustrating the normal banding pattern seen in cytogenetic studies. Human chromosomes contain a short (‘p’) arm and a long (‘q’) arm, separated by a structure called a centromere. The red bar shows the DYX1 region, identified by linkage and association studies of dyslexia, corresponding to cytogenetic bands 15q15-21. The bottom half of the figure shows the genomic organisation of the DYX1C1 gene (previously known as EKN1), spanning w78 thousand nucleotides in 15q21. Boxes indicate exons (included in the mature RNA transcript), lines indicate introns (removed by splicing), and the arrow shows the direction of transcription. (Note that exons and introns are not shown to the same scale here; some of the introns are very large.) Black shading indicates exons that are not translated into protein sequences (non-coding exons) upstream and downstream of the proteincoding region. Taipale and colleagues [10] studied a Finnish family in which dyslexia was associated with a gross chromosomal rearrangement known as a translocation; one end of chromosome 15 had been exchanged with part of chromosome 2 in the affected individuals. The site of breakage lies somewhere within the purple-shaded region of the DYX1C1 gene. Taipale et al. identified -3Gto-A and 1249G-to-T SNPs in other Finnish families with dyslexia [10], but further studies demonstrated that these are unlikely to represent functional risk alleles [31– 36]. (Ideograms are adapted from http://www.pathology.washington.edu/research/](/figures/figure-1-the-dyx1c1-gene-an-ideogram-of-chromosome-15-is-2fzuj3jb.webp)
![Figure 2. The KIAA0319 and DCDC2 (doublecortin domain containing 2) genes. An ideogram of chromosome 6 is shown at the top, with ‘p’ and ‘q’ arms indicated. The red bar shows the DYX2 consensus region identified in initial linkage/association studies of dyslexia, corresponding to cytogenetic bands 6p23-p21.3. Recent studies converged on a region of 6p22.2 which includes two nearby gene clusters, one containing VMP, DCDC2 and KAAG1, the other containing KIAA0319, TTRAP and THEM2. The region shown in this figure spans approximately 576 thousand nucleotides, and genes are drawn to scale, with directions of transcription indicated. (Note that the exon-intron organisation of these genes is not illustrated here.) Whereas some research groups find evidence supporting involvement of KIAA0319 in dyslexia susceptibility [11–13], others favour a role for DCDC2 [14,15].](/figures/figure-2-the-kiaa0319-and-dcdc2-doublecortin-domain-peop9xy4.webp)
Q2. What are the future works mentioned in the paper "Genes, cognition and dyslexia: learning to read the genome" ?
Questions for future research † It is hoped that further studies will help to explain why aetiological variants disturb reading while generally preserving broader aspects of cognition ( see Box 3 ). Early suggestions that different genes might have specific separable effects on these processes have not held up, but it remains plausible that risk alleles impact more strongly on certain phenotypic aspects than on others. Does genetic profile influence the response of an individual to particular behavioural interventions, and will the authors ever be able to target therapies based on an individual ’ s genetic information ?
Q3. What is the role of the splicing process in mammalian cancers?
Mammalian ROBO1, which is assembled into several forms via a process called alternative splicing, is implicated in mammalian cancers [66,67].
Q4. What methods have been used to analyze the severity of dyslexia?
Linkage and association methods have also been adapted for analyzing quantitative indices of severity (e.g. performance on reading-related tasks) [8].
Q5. How many nucleotide letters will not match?
Connecting genes with cognitionOn average, if you line up your DNA with that of an unrelated neighbour, w3 million nucleotide letters (approximately 0.1% of your genome) will not match.
Q6. What is the role of neuroimaging in dyslexia?
It is already clear that synergy between molecular approaches and distinct forms of enquiry, like neuroimaging and behavioural studies, will be powerful both for improving prospects of treating dyslexia and for uncovering neural pathways that contribute to reading.
Q7. Why are some variants in adjacent genetic markers analyzed together?
Because specific allelic variants in adjacent genetic markers tend to be inherited together they are sometimes analyzed together in combinations that are known as ‘haplotypes’.
Q8. What is the aetiological argument for KIAA0319?
Both genes have neural functions that are compatible with the dyslexia phenotype; by reducing expression in utero in rat brain, it has been shown that neuronal migration is impaired by interfering with either KIAA0319 [13] or DCDC2 [14].
Q9. What other family has a linkage to chromosome 2?
(Other reports of apparent simple inheritance include a Norwegianfamily showing chromosome-2 linkage [51] and a Dutch family showing chromosome-X linkage [52].)
Q10. What is the role of genes in dyslexia?
During the past decade, advances in human molecular genetics have allowed researchers to track down chromosomal sites that might harbour factors involved in dyslexia predisposition (reviewed in [6–9]).
Q11. How many individuals can be required to identify the relevant genes?
Complex genetic traits involve multiple factors with potentially subtle effects, so large samples (perhaps thousands of individuals) can be required to pinpoint the relevant genes.
Q12. What is the way to compare amino acid changes with protein sequence?
the number of nucleotide changes that alter amino-acids should be compared with the number of ‘silent’ changes that preserve protein sequence.
Q13. What is the difficult task to learn to read?
Unlike the virtually effortless and automatic acquisition of spoken language during the first few years of life, learning to read is a challenging task that requires extensive tuition.