互补测试鉴定了与恐惧相关行为的数量性状基因座相关效应的基因。

Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.

机构信息

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Department of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Cell Genom. 2024 May 8;4(5):100545. doi: 10.1016/j.xgen.2024.100545. Epub 2024 May 1.

DOI:10.1016/j.xgen.2024.100545

PMID:38697120

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11099346/

Abstract

Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.

摘要

了解涉及数量性状的基因为理解行为的生物学基础提供了一个切入点，但已知的从遗传基因座到行为变化的途径非常少。为了探索特定基因在恐惧行为中的作用，我们绘制了三个与恐惧相关的特征，通过定量互补测试了六个数量性状基因座 (QTL) 中的 14 个基因，并鉴定了六个基因。四个基因 Lamp、Ptprd、Nptx2 和 Sh3gl 在突触功能方面具有已知作用；第五个基因 Psip1 以前没有涉及行为；第六个是一个长非编码 RNA，4933413L06Rik，其功能未知。转录组和表观遗传方式的变异主要发生在兴奋性神经元中，这表明遗传变异在兴奋性神经元回路中比在抑制性神经元回路中更具可接受性。我们的结果缓解了使用 QTL 的遗传图谱来揭示行为背后的生物学的瓶颈问题，并促使人们重新考虑遗传和功能变异之间的预期关系。