Genome wide association analysis in a mouse advanced intercross line

Natalia M.  Gonzales; Jungkyun  Seo; Ana Hernandez Cordero; Celine  St. Pierre; Jennifer Gregory; Margaret Distler; Mark Abney; Stefan  Canzar; Arimantas Lionikas; Abraham Palmer

doi:10.1038/s41467-018-07642-8

Genome wide association analysis in a mouse advanced intercross line

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

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Abstract

The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands of cis- and trans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ~200 mice. We replicate an association between locomotor activity and Csmd1, which we identified in an earlier generation of this AIL, and show that Csmd1 mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.

Original language	English
Article number	5162
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-07642-8
Publication status	Published - 4 Dec 2018

Bibliographical note

We are grateful to Heather Lawson at Washington University in St. Louis for providing LG and SM genome sequences. We thank the Gilad Lab and Functional Genomics Facility at the University of Chicago for generating DNA- and RNA-seq data. We wish to acknowledge outstanding technical assistance from Apurva Chitre at UCSD and Mike Jarsulic at the Biological Sciences Division Center for Research Informatics at the University of Chicago. We thank Clarissa Parker, John Novembre, Graham McVicker, Joe Davis, Peter Carbonetto and Shyam Gopalakrishnan for advice, training, and mentorship. Our work was funded by NIDA (AAP: R01DA021336) and NIAMS (AL: R01AR056280). We received additional support from NIGMS (NMG: T32GM007197; MGD: T32GM07281), NIDA (NMG: F31DA03635803), NHGRI (MA: R01 HG002899), and the IMS Elphinstone Scholarship at the University of Aberdeen (AIHC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Keywords

behavioural genetics
genetic association study
genetics
heritable quantitative trait
quantitative trait

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Genome wide association analysis in a mouse advanced intercross line
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Arimantas Lionikas
Person: Academic

Cite this

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abstract = "The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands of cis- and trans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ~200 mice. We replicate an association between locomotor activity and Csmd1, which we identified in an earlier generation of this AIL, and show that Csmd1 mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.",

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AU - Distler, Margaret

AU - Abney, Mark

AU - Canzar, Stefan

AU - Lionikas, Arimantas

AU - Palmer, Abraham

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KW - heritable quantitative trait

KW - quantitative trait

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Genome wide association analysis in a mouse advanced intercross line

Abstract

Bibliographical note

Keywords

UN SDGs

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Arimantas Lionikas

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