Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity

Abstract The WMI and WLI inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain. These were selected using bi-directional selection for immobility in the forced swim test and were then sib-mated for over 38 generations. Despite the low level of genetic...

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Autores principales:	Tristan V. de Jong, Panjun Kim, Victor Guryev, Megan K. Mulligan, Robert W. Williams, Eva E. Redei, Hao Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8eb44956bc7749e0b76370da72aeaff9
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spelling	oai:doaj.org-article:8eb44956bc7749e0b76370da72aeaff92021-12-02T16:26:29ZWhole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity10.1038/s41598-021-92993-42045-2322https://doaj.org/article/8eb44956bc7749e0b76370da72aeaff92021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92993-4https://doaj.org/toc/2045-2322Abstract The WMI and WLI inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain. These were selected using bi-directional selection for immobility in the forced swim test and were then sib-mated for over 38 generations. Despite the low level of genetic diversity among WKY progenitors, the WMI substrain is significantly more vulnerable to stress relative to the counter-selected WLI strain. Here we quantify numbers and classes of genomic sequence variants distinguishing these substrains with the long term goal of uncovering functional and behavioral polymorphism that modulate sensitivity to stress and depression-like phenotypes. DNA from WLI and WMI was sequenced using Illumina xTen, IonTorrent, and 10X Chromium linked-read platforms to obtain a combined coverage of ~ 100X for each strain. We identified 4,296 high quality homozygous SNPs and indels between the WMI and WLI. We detected high impact variants in genes previously implicated in depression (e.g. Gnat2), depression-like behavior (e.g. Prlr, Nlrp1a), other psychiatric disease (e.g. Pou6f2, Kdm5a, Reep3, Wdfy3), and responses to psychological stressors (e.g. Pigr). High coverage sequencing data confirm that the two substrains are nearly coisogenic. Nonetheless, the small number of sequence variants contributes to numerous well characterized differences including depression-like behavior, stress reactivity, and addiction related phenotypes. These selected substrains are an ideal resource for forward and reverse genetic studies using a reduced complexity cross.Tristan V. de JongPanjun KimVictor GuryevMegan K. MulliganRobert W. WilliamsEva E. RedeiHao ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tristan V. de Jong Panjun Kim Victor Guryev Megan K. Mulligan Robert W. Williams Eva E. Redei Hao Chen Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
description	Abstract The WMI and WLI inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain. These were selected using bi-directional selection for immobility in the forced swim test and were then sib-mated for over 38 generations. Despite the low level of genetic diversity among WKY progenitors, the WMI substrain is significantly more vulnerable to stress relative to the counter-selected WLI strain. Here we quantify numbers and classes of genomic sequence variants distinguishing these substrains with the long term goal of uncovering functional and behavioral polymorphism that modulate sensitivity to stress and depression-like phenotypes. DNA from WLI and WMI was sequenced using Illumina xTen, IonTorrent, and 10X Chromium linked-read platforms to obtain a combined coverage of ~ 100X for each strain. We identified 4,296 high quality homozygous SNPs and indels between the WMI and WLI. We detected high impact variants in genes previously implicated in depression (e.g. Gnat2), depression-like behavior (e.g. Prlr, Nlrp1a), other psychiatric disease (e.g. Pou6f2, Kdm5a, Reep3, Wdfy3), and responses to psychological stressors (e.g. Pigr). High coverage sequencing data confirm that the two substrains are nearly coisogenic. Nonetheless, the small number of sequence variants contributes to numerous well characterized differences including depression-like behavior, stress reactivity, and addiction related phenotypes. These selected substrains are an ideal resource for forward and reverse genetic studies using a reduced complexity cross.
format	article
author	Tristan V. de Jong Panjun Kim Victor Guryev Megan K. Mulligan Robert W. Williams Eva E. Redei Hao Chen
author_facet	Tristan V. de Jong Panjun Kim Victor Guryev Megan K. Mulligan Robert W. Williams Eva E. Redei Hao Chen
author_sort	Tristan V. de Jong
title	Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
title_short	Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
title_full	Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
title_fullStr	Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
title_full_unstemmed	Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity
title_sort	whole genome sequencing of nearly isogenic wmi and wli inbred rats identifies genes potentially involved in depression and stress reactivity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8eb44956bc7749e0b76370da72aeaff9
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Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity

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