Transcriptomic Comparison of Lissencephaly-related Genes: From Correlation to Clinical Relevance

ÖzObjective: Lissencephaly is a neurodevelopmental disorder resulting from genetic and cellular defects in neuronal migration processes.In this study, correlation-based gene networks were analyzed to understand the functional and cellular relationships of lissencephaly-associated genes.Methods: Hierarchical clustering and genetic network analyses based on Jaccard indices and Spearman's rank correlation were performed using fetal brain gene expression data from Allen Brain Atlas.These analyses identified functional similarities between gene pairs and suggested potential shared roles in cortical developmental processes.Results: Hierarchical clustering analysis confirmed known associations, such as those between tubulins and microtubule-associated genes involved in migration and layering processes.Genes that relay extracellular signals to the migrating cells, such as Reelin and very low-density lipoprotein receptor, were observed to form a separate group.Using t-distributed stochastic neighbor embedding analyses of single-cell RNA sequencing data, specific expression patterns of these genes in brain cellular subpopulations were compared.Correlation network graphs showed that genes such as PAFAH1B1 and TUBG1 play central roles in cortical development, whereas genes such as CRADD and ARX have more specific functions.Conclusion: These findings explain the relationships of lissencephaly-related genes with each other and their functional connections in neuronal migration processes.This study provides new perspectives for understanding the mechanisms of cortical development and points to previously unknown associations.