Orthographic differences across languages impose differential weighting on distinct component processes, and consequently on different pathways during word-reading tasks. Readers of transparent orthographies such as Italian and Hindi are thought to rely on spelling-to-sound assembly and show increased activation in phonologically-tuned areas along the dorsal pathway, whereas reading an opaque orthography such as English is thought to rely more on lexically-mediated processing associated with increased activation of semantically-tuned regions along the ventral pathway. To test if biliterate Hindi/English readers exhibit orthography-specific reading pathways, we used behavioural measures and functional neuroimaging. Reaction times and activation patterns of monolingual English and Hindi readers were compared to two groups of adult biliterates; 14 simultaneous readers who learnt to read both languages at age 5 and 10 sequential readers who learnt Hindi at 5 and English at 10. Simultaneous, but not sequential readers demonstrated relative activation differences of dorsal and ventral areas in the two languages. Similar to native counterparts, simultaneous readers preferentially activated the left inferior temporal gyrus for English and left inferior parietal lobule (L-IPL) for Hindi, whereas, sequential readers showed higher activation along the L-IPL for reading both languages. We suggest that early simultaneous exposure to reading distinct orthographies results in orthography-specific plasticity that persists through adulthood.

A 3.5-Mb region of the X chromosome underwent duplication and transposition to the Y chromosome ~5-6 Mya. This X-transposed-region (XTR) originated at Xq21.3 and was inserted at Yp11.2. The two locations have 98.78 % homology and a high concentration of tandem repeats. In whole-genome scans of ten large families with dyslexic members, we identified transposed blocks comprising >102 kb of the Yp11.2 region in its homologous region at Xq21.3 in three females from three different families. Although recombination is known to be limited only to the pseudoautosomal regions (PARs) of the X and Y chromosomes, we report allelic unequal recombination between the XTR region Yp11.2 and Xq21.3, indicating the presence of a new PAR, which we named PAR3. This PAR3 region was also found in 2 % of the general population. An additional layer of justification could be provided from six other dyslexic cases which harbored duplications and deletions in the same Xq21.3 and Yp11.2 regions through allelic unequal recombination.

Developmental dyslexia (DD) is a heritable, complex genetic disorder associated with impairment in reading and writing skills despite having normal intellectual ability and appropriate educational opportunities. Chromosome 6p23-21.3 at DYX2 locus has showed the most consistent evidence of linkage for DD and two susceptible genes KIAA0319 and DCDC2 for DD at DYX2 locus showed significant association. Specific candidate gene-association studies have identified variants, risk haplotypes and microsatellites of KIAA0319 and DCDC2 correlated with wide range of reading-related traits. In this study, we used a case-control approach for analyzing single-nucleotide polymorphisms (SNPs) in KIAA0319 and DCDC2. Our study demonstrated the association of DD with SNP rs4504469 of KIAA0319 and not with any SNPs of DCDC2.

Genome-wide screening for copy number variations (CNVs) in ten Indian dyslexic families revealed the presence of five de novo CNVs in regions harboring GABARAP, NEGR1, ACCN1, DCDC5, and one in already known candidate gene CNTNAP2. These genes are located on regions of chromosomes 17p13.1, 1p31.1, 17q11.21, 11p14.1 and 7q35, respectively, and are implicated in learning, cognition and memory processes through dendritic spinal plasticity, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia-related module genes suggests them to be associated with synaptic transmission, axon guidance and cell adhesion. Thus, we suggest that dyslexia may also be caused by neuronal disconnection in addition to the earlier view that it is due to neuronal migrational disorder. Keywords: CNVs in dyslexia; dyslexia network; synaptic plasticity INTRODUCTION Developmental dyslexia (DD) (MIM#127700) is a common neurogenetic disorder that affects 5-12% of school-aged children. 1,2 The major deficit is impaired phonological processing, which interferes with the mapping between orthography and phonology. Linkage studies have identified nine following regions on different chromosomes for DD (DYX1-DYX9): DYX1 on 15q21 contains DYX1C1; DYX2 on 6p22.2-p21.3 contains DCDC2 and KIAA0319; DYX3 on 2p16-p15 contains MRPL19 and C2ORF3; DYX4 on 6q11.2-q12; DYX5 on 3p12-q13 contains ROBO1; DYX6 on 18p11.2; DYX7 on 11p15.5; DYX8 on 1p36-p34 contains KIAA0319L and DYX9 on Xq27.2-q28. 3 These loci were identified in samples covering the American, Canadian, British, German and the Finnish families. A growing body of evidence suggests that structural variations across the genome, including copy number variations (CNVs) likely contributes to human disorders. 4,5 CNVs refer to the presence of DNA segments longer than 1 kb with 490% sequence identity that differ in the number of copies between the genomes of different individuals. 6 It affects more nucleotides per genome than single-nucleotide polymorphism (SNP), and contributes significantly to variations in levels of gene expression and phenotypes of medical relevance among individuals. 7 Even in studies that have shown negative linkage, the possible contribution of undetected CNVs cannot be dismissed. 3 Genome-wide screenings for CNVs have demonstrated that deletions and duplications that disrupt gene functioning are found more in patients than in healthy subjects. [8][9][10][11][12][13]

Developmental dyslexia (DD) is a complex neuro-genetic disorder associated with difficulty in learning to read despite adequate intelligence and educational opportunities. Studies in different populations have established associations between DD and single nucleotide polymorphisms (SNPs) in a number of candidate genes, including DYX1C1, KIAA0319 and DCDC2. In an ongoing DD study in India, we screened twenty SNPs located within the coding region of these three candidate genes by mass-ARRAY technique. At this point, there is no statistical evidence of association between the allelic variation in the three candidate genes and DD in our sample, although there might be some promising leads for future research that should involve a large and a better characterized sample.