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bioRxiv · 10.1101/2025.05.21.655339

The study of differential expressions of MCPH and Seckel syndrome genes and their paralogues

Khurshid, M.·Mohsin, M.·Riaz, S.·Imran, M.·Cox, J. J.
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Abstract

Seckel syndrome and MCPH are single-gene neurodevelopmental disorders, with or without dwarfism. These genes are parts of essential cellular pathways but are regulated differently in both forms of microcephaly. These genes have diverged from single ancestral genes in to related but different gene paralogues during evolution. It is suggested that the paralogues might be redundant in other body organs and might rescue any abnormality in cases of MCPH, but not in Seckel syndrome. This study uncovers the spatio-temporal dynamics of these genes together with their paralogues at the mRNA level where the different tissues of embryos might exhibit different transcript variants or different levels of the various transcript variants to find the complementation in case of the MCPH but divergence in case of the Seckel syndrome. Here, we studied Cdk5Rap2-Pde4dip, Phc1-Phc3 (for MCPH) and Cep63-Ccdc67 (for Seckel) in the embryonic mouse tissues using RT-PCR throughout the peak of neurogenesis from E12.5 to E18.5. We found already known and novel spatio-temporal differential expression suggesting different regulation at the mRNA level. The results of PCR were analyzed on the agarose gel and were quantified by assigning relative intensity percentage scores to each band and plotting the cumulative expression of each gene in to the graphs for spatio-temporal dynamics and plotted each gene separately for temporal dynamics. For MCPH, Cdk5Rap2-Pde4dip had similar profiles and seemed to be redundant whereas Phc1-Phc3 seem to have complementary roles in brain development. The expression profiles of Cep63-Ccdc67 were very different indicating of their divergent and essential roles in development.

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Khurshid, M., Mohsin, M., Riaz, S., Imran, M., Cox, J. J.. 2025-05-27. The study of differential expressions of MCPH and Seckel syndrome genes and their paralogues. https://doi.org/10.1101/2025.05.21.655339

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