Dyslexia risk variant rs600753 is linked with dyslexia-specific differential allelic expression of DYX1C1

Abstract

An increasing number of genetic variants involved in dyslexia development were discovered during the last years, yet little is known about the molecular functional mechanisms of these SNPs. In this study we investigated whether dyslexia candidate SNPs have a direct, disease-specific effect on local expression levels of the assumed target gene by using a differential allelic expression assay. In total, 12 SNPs previously associated with dyslexia and related phenotypes were suitable for analysis. Transcripts corresponding to four SNPs were sufficiently expressed in 28 cell lines originating from controls and a family affected by dyslexia. We observed a significant effect of rs600753 on expression levels of DYX1C1 in forward and reverse sequencing approaches. The expression level of the rs600753 risk allele was increased in the respective seven cell lines from members of the dyslexia family which might be due to a disturbed transcription factor binding sites. When considering our results in the context of neuroanatomical dyslexia-specific findings, we speculate that this mechanism may be part of the pathomechanisms underlying the dyslexia-specific brain phenotype. Our results suggest that allele-specific DYX1C1 expression levels depend on genetic variants of rs600753 and contribute to dyslexia. However, these results are preliminary and need replication.

Dyslexia‐Related Hearing Loss Occurs Mainly through the Abnormal Spontaneous Electrical Activity of Spiral Ganglion Neurons

“…[8] At present, the Dyx1c1 −/− mouse is an ideal model of dyslexia and is widely used to study the pathogenesis of dyslexia-related deficits. [27][28][29][30][31] Knockdown of Dyx1c1 in rat embryos leads to the loss of the ability of the neocortical neurons to migrate to the proper position, indicating that Dyx1c1 is essential for nervous system development. [32] Further studies showed that Dyx1c1 knockdown in the forebrain of the mouse resulted in impairment of learning and memory, indicating that Dyx1c1 is critical for the development of the learning and memory part of the brain.…”