Variations in genes regulating neuronal migration predict reduced prefrontal cognition in schizophrenia and bipolar subjects from mediterranean Spain: a preliminary study.

Both neural development and prefrontal cortex function are known to be abnormal in schizophrenia and bipolar disorder. In order to test the hypothesis that these features may be related with genes that regulate neuronal migration, we analyzed two genomic regions: the lissencephaly critical region (chromosome 17p) encompassing the LIS1 gene and which is involved in human lissencephaly; and the genes related to the platelet-activating-factor, functionally related to LIS1, in 52 schizophrenic patients, 36 bipolar I patients and 65 normal control subjects. In addition, all patients and the 25 control subjects completed a neuropsychological battery. Thirteen (14.8%) patients showed genetic variations in either two markers related with lissencephaly or in the platelet-activating-factor receptor gene. These patients performed significantly worse in the Wisconsin Card Sorting Test-Perseverative Errors in comparison with patients with no lissencephaly critical region/platelet-activating-factor receptor variations. The presence of lissencephaly critical region/platelet-activating-factor receptor variations was parametrically related to perseverative errors, and this accounted for 17% of the variance (P = 0.0001). Finally, logistic regression showed that poor Wisconsin Card Sorting Test-Perseverative Errors performance was the only predictor of belonging to the positive lissencephaly critical region/platelet-activating-factor receptor group. These preliminary findings suggest that the variations in genes involved in neuronal migration predict the severity of the prefrontal cognitive deficits in both disorders.

On the function of modified nucleosides in the RNA world.

Presumably ribosome and transfer RNA (tRNA) evolved from a pre-existing function in the RNA stage of life and were secondarily adapted for protein synthesis. Various possible initial functions of the primitive ribosome (protoribosome) have been suggested. The initial function of the primitive ribosome and primitive genetic translation would have been quite similar. It is possible that, initially, both functions coexisted in the protoribosome. Given that the three-dimensional structure of ribosomal RNAs shows only minor variations throughout time, it is, then, most likely that present ribosomes can still recall (remember) the most important parts of the mechanism of their initial function. A process would have arisen to inactivate the initial function of the protoribosome without affecting genetic translation: the modification of some ribosome nucleosides. We suggest that the modifications of some rRNA nucleosides located in the catalytic center responsible for the initial function of primitive ribosomes, and of some of the tRNA nucleosides which interacted with the same center could have resulted in the inability of their recognition and secondary interaction. Thus, it is a known fact that the establishing of hydrogen bonds between modified nucleosides is rare and unstable. Therefore, the initial biological function of primitive ribosomes could have been inactivated without significantly affecting its three-dimensional structure. Therefore, without affecting the primitive translation. After the emergence of translation, some catalytic proteins (enzymes) which could modify the nucleosides of ribozymes could have arisen. In brief, we suggest that the catalytic proteins, through nucleoside modification, inactivated the catalytic RNA activity but RNA capacity to recognize and to bind other RNAs was not essentially altered. Only a few ribozymes were slightly affected by the modifications and they still maintain catalytic and binding activities. Therefore, we suggest that the proteins, through modification process, could have diminished the diverse functional capacities of the first RNA molecules. Auto-organization of the organic matter could be based on this type of interaction between macromolecules (protein and RNA).