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.
Highlights
The WKY More Immobile (WMI) and WKY Less Immobile (WLI) inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain
We were interested in variants that have a Phred quality score above 30, have a clear call for either reference, homozygous or heterozygous, have no matching calls between WLI and WMI and must not have both a high quality reference and alternative allele called on different sequencing platforms within the same strain (Fig. 1)
We used three leading next-generation sequencing technologies to obtain a combined coverage of approximately 100X for each genome of two closely related inbred rat strains, the WMI and WLI
Summary
The WMI and WLI inbred rats were generated from the stress-prone, and not yet fully inbred, Wistar Kyoto (WKY) strain. 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. 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. Its behavior mirrors several symptoms of human MDD and anxiety, including anhedonia, disturbed sleep, a reduced appetite and reduced energy, and the attenuation of depression-like behaviors after treatment with a ntidepressants[21,22,23,24,25,26]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
