Department of Anthropology, New York University, New York, NY, USA; New York Consortium in Evolutionary Primatology, New York, NY, USA; Section on Developmental Neurogenomics, National Institute of Mental Health, Bethesda, MD, USA.
Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA; School of Life Sciences, Arizona State University, Tempe, AZ, USA; Department of Psychology, University of Washington, Seattle, WA, USA; Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Washington, Seattle, WA, USA.
Cell Genom. 2024 Jul 10;4(7):100589. doi: 10.1016/j.xgen.2024.100589. Epub 2024 Jun 27.
Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.
人类在许多神经发育障碍和神经退行性疾病的患病率上存在性别差异。在这里,我们生成了恒河猴最大的多脑区批量转录组数据集之一,并对性别偏倚的基因表达模式进行了特征描述,以研究该物种在性别偏倚的神经疾病方面的可转化性。我们发现了与人类相似的模式,这些模式与重叠的调控机制、生物学过程以及与性别偏倚的人类疾病(包括自闭症)相关的基因有关。我们还表明,性别偏倚的基因在表达方面具有更大的遗传方差和更具组织特异性的表达模式,这可能有助于性别偏倚基因的快速进化。我们的研究结果为性别偏倚疾病的生物学机制提供了新的见解,并支持恒河猴模型作为这些疾病的转化研究模型。