Document Type : Original Article
Authors
1
School of Biology, College of Science, University of Tehran, Tehran, Iran
2
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
10.22074/cellj.2024.2018050.1471
Abstract
Abstract
Objective
The prevalence of neurological disorders often varies by sex, with conditions such as Alzheimer’s disease and Autism Spectrum Disorder (ASD) demonstrating notable differences in incidence. Understanding the molecular basis for these divergences could facilitate the creation of sex-specific therapeutic strategies.
Methods
The study utilized RNA sequencing data from postmortem human brains’ prefrontal cortex, including 38 neurotypical controls and 34 individuals with ASD. The sequencing data was obtained from previously published papers, and we downloaded the raw data from SRA. We investigated the molecular basis of sex-biased presentation in ASD through comprehensive transcriptomic analysis.
Results
Comparative analysis of gene expression between male and female subjects, both autistic and unaffected, was conducted, using a significance cutoff of ≤0.01. In autistic individuals, 136 genes demonstrated differential expression between sexes, predominantly upregulated in males, indicating a bias in male gene expression. Among these, 12 genes were identified as risk factors in the SFARI dataset. While most sex-biased genes were autosomal, expression differences on sex chromosomes were also observed in neurotypical subjects. Notable genes included TCF7L2, collagen family genes, and solute carrier family genes. In ASD males, extracellular matrix organization emerged as a significant pathway, while immune-related processes were prominent in unaffected individuals.
Conclusion
Our study highlights the impact of the extracellular matrix pathway in ASD, with notable differences between sexes, particularly in males. MIR424 shows promise as a potential biomarker for ASD in males. Recognizing the importance of sex differences in ASD transcriptomic research is crucial, as these variances provide insights into the disorder’s pathophysiology and may guide the development of more personalized treatments for both sexes.
Keywords
Main Subjects
', './data/cellj/coversheet/cover_en.jpg'))