https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=34285244&retmode=xml&tool=Litmetric&email=readroberts32@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09 342852442021111520230928
2045-23221112021Jul20Scientific reportsSci RepWhole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity.14774147741477410.1038/s41598-021-92993-4The 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.© 2021. The Author(s).de JongTristan VTVUniversity of Tennessee Health Science Center, Memphis, TN, USA.KimPanjunPUniversity of Tennessee Health Science Center, Memphis, TN, USA.GuryevVictorVEuropean Research Institute for the Biology of Ageing, University of Groningen, Groningen, The Netherlands.MulliganMegan KMKUniversity of Tennessee Health Science Center, Memphis, TN, USA.WilliamsRobert WRWUniversity of Tennessee Health Science Center, Memphis, TN, USA.RedeiEva EEENorthwestern University - Chicago, Chicago, IL, USA.ChenHaoHUniversity of Tennessee Health Science Center, Memphis, TN, USA. hchen@uthsc.edu.engR01 DA048017DANIDA NIH HHSUnited StatesComparative StudyJournal ArticleResearch Support, N.I.H., Extramural20210720
EnglandSci Rep1015632882045-2322IMAnimalsDepressiongeneticsDisease Models, AnimalFemaleGene Regulatory NetworksGenetic VariationHigh-Throughput Nucleotide SequencingINDEL MutationMalePhenotypePolymorphism, Single NucleotideRatsRats, Inbred StrainsRats, Inbred WKYStress, PsychologicalgeneticsWhole Genome SequencingmethodsThe authors declare no competing interests.2021222202161720217216020217226020211116602021720epublish34285244PMC829248210.1038/s41598-021-92993-410.1038/s41598-021-92993-4WHO . Disease Burden and Mortality Estimates. Geneva: WHO; 2018.Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: Review and meta-analysis. Am. J. Psychiatry. 2000;157:1552–1562. doi: 10.1176/appi.ajp.157.10.1552.10.1176/appi.ajp.157.10.155211007705Fernandez-Pujals AM, et al. 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