DCDC2 is associated with reading disability and modulates neuronal development in the brain.
Meng, H., Smith, S.D., Hager, K. et al. Proc. Nat. Acad. Sci., 102(47), 17053-17058 (November 22, 2005).
Genetic factors underlying reading disability (RD) have not been well characterized, but the DYX2 locus has been well linked to the problem. The current report sheds further light on the subject by identifying a gene in the DYX2 locus that creates susceptibility to developing RD.
Using a marker panel of 147 single nucleotide polymorphisms in a 1.5 Mb span near marker JA04, the authors searched for genes that correlated with RD in 536 samples from 153 families at the Colorado Learning Disabilities Research Center. Two SNPs in DCDC2 were found to correlate significantly with RD susceptibility, and a previously uncharacterized deletion in the region designated as C_449792, was identified in intron 2 of DCDC2 of genes from 10 families. The deletion, spanning 2,445 bp, is located between regions coding for DCX doublecortin peptide.
Quantitative real-time RT-PCR found DCDC2 to be one of the most variably expressed genes, out of eight studied, in 17 regions of human brain. The gene was most highly expressed in the entorhinal cortex, inferior temporal cortex, medial temporal cortex, hypothalamus, amygdala, and hippocampus.
The functional role of the DCDC2 gene was then investigated by studying the effect of an RNAi to the gene on development of the neocortex in utero. Transfection slowed neuronal migration from the surface of the ventrical, where mitosis occurs, to the pial surface, where the cortex is forming.
The studies show that the deletion in the DCDC2 gene alters the normal development of the neocortex, which, in turn, predisposes individuals to RD. However, because no gross brain abnormalities were found in the RNAi experiments, the DCDC2 gene product appears to play a modulatory role in neuronal migration, unlike the DCX gene’s doublecortin, which plays a pivotal role in normal cortical development.
Message posted by: Keith Markey
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