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

QTL mapping fear conditioning inbred mouse strains quantitative complementation single-nucleus ATAC-seq single-nucleus RNA-seq

Journal

Cell genomics
ISSN: 2666-979X
Titre abrégé: Cell Genom
Pays: United States
ID NLM: 9918284260106676

Informations de publication

Date de publication:
22 Apr 2024
Historique:
received: 03 01 2024
revised: 23 02 2024
accepted: 04 04 2024
medline: 3 5 2024
pubmed: 3 5 2024
entrez: 2 5 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.xgen.2024.100545 PMID: 38697120
pubmed: 38697120
pii: S2666-979X(24)00101-0
doi: 10.1016/j.xgen.2024.100545
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100545

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Patrick B Chen (PB)

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

Rachel Chen (R)

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

Nathan LaPierre (N)

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.

Zeyuan Chen (Z)

Department of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA.

Joel Mefford (J)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Emilie Marcus (E)

Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.

Matthew G Heffel (MG)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Daniela C Soto (DC)

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

Jason Ernst (J)

Department of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.

Chongyuan Luo (C)

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Jonathan Flint (J)

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: jflint@mednet.ucla.edu.

Classifications MeSH