Data Set Group2: UCSD AIL Advanced Intercross Line (Apr18) RNA-Seq

Data Set: UCSD AIL Hippocampus (Apr18) RNA-Seq GN Accession: GN844 GEO Series: No Geo series yet Title: Genome wide association study of behavioral, physiological and gene expression traits in a multigenerational mouse intercross Organism: Mouse (Mus musculus, mm10) Group: LGSM-AI Tissue: Hippocampus mRNA Dataset Status: Public Platforms: Illumina ScriptSeq RNA-Seq v2 Normalization: RNA-seq

Contact Information Abraham Palmer University of California, San Diego 9500 Gilman Drive #0667 La Jolla, CA 92093 USA Tel. 858-534-2093 aapalmer@ucsd.edu Website Download datasets and supplementary data files

Specifics of this Data Set:

Hippocampus

Summary:

Genome wide association analyses (GWAS) in model organisms have numerous advantages compared to human GWAS, including the ability to use populations with well-defined genetic diversity, the ability to collect tissue for gene expression analysis and the ability to perform experimental manipulations. We examined behavioral, physiological, and gene expression traits in 1,063 male and female mice from a 50-generation intercross between two inbred strains (LG/J and SM/J). We used genotyping by sequencing in conjunction with whole genome sequence data from the two founder strains to obtain genotypes at 4.3 million SNPs. As expected, all alleles were common (mean MAF=0.35) and linkage disequilibrium degraded rapidly, providing excellent power and sub-megabase mapping precision. We identified 126 genome-wide significant loci for 50 traits and integrated this information with 7,081 cis-eQTLs and 1,476 trans-eQTLs identified in hippocampus, striatum and prefrontal cortex. We replicated several loci that were identified using an earlier generation of this intercross, including an association between locomotor activity and a locus containing a single gene, Csmd1. We also showed that Csmd1 mutant mice recapitulated the locomotor phenotype. Our results demonstrate the utility of this population, identify numerous novel associations, and provide examples of replication in an independent cohort, which is customary in human genetics, and replication by experimental manipulation, which is a unique advantage of model organisms.

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Contributor:

Natalia M. Gonzales, Jungkyun Seo, Ana Isabel Hernandez-Cordero, Celine L. St. Pierre, Jennifer S. Gregory, Margaret G. Distler, Mark Abney, Stefan Canzar, Arimantas Lionikas, Abraham A. Palmer

Citation:

Genome wide association study of behavioral, physiological and gene expression traits in a multigenerational mouse intercross

Data source acknowledgment:

Study Id:

272

• The UT Center for Integrative and Translational Genomics
• NIGMS Systems Genetics and Precision Medicine project (R01 GM123489, 2017-2021)
• NIDA NIDA Core Center of Excellence in Transcriptomics, Systems Genetics, and the Addictome (P30 DA044223, 2017-2022)
• NIA Translational Systems Genetics of Mitochondria, Metabolism, and Aging (R01AG043930, 2013-2018)
• NIAAA Integrative Neuroscience Initiative on Alcoholism (U01 AA016662, U01 AA013499, U24 AA013513, U01 AA014425, 2006-2017)
• NIDA, NIMH, and NIAAA (P20-DA 21131, 2001-2012)
• NCI MMHCC (U01CA105417), NCRR, BIRN, (U24 RR021760)