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Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies
Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats t...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187121/ https://www.ncbi.nlm.nih.gov/pubmed/35639796 http://dx.doi.org/10.1371/journal.pgen.1010234 |
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author | Gileta, Alexander F. Fitzpatrick, Christopher J. Chitre, Apurva S. St. Pierre, Celine L. Joyce, Elizabeth V. Maguire, Rachael J. McLeod, Africa M. Gonzales, Natalia M. Williams, April E. Morrow, Jonathan D. Robinson, Terry E. Flagel, Shelly B. Palmer, Abraham A. |
author_facet | Gileta, Alexander F. Fitzpatrick, Christopher J. Chitre, Apurva S. St. Pierre, Celine L. Joyce, Elizabeth V. Maguire, Rachael J. McLeod, Africa M. Gonzales, Natalia M. Williams, April E. Morrow, Jonathan D. Robinson, Terry E. Flagel, Shelly B. Palmer, Abraham A. |
author_sort | Gileta, Alexander F. |
collection | PubMed |
description | Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (F(ST) > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted for population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies. |
format | Online Article Text |
id | pubmed-9187121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-91871212022-06-11 Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies Gileta, Alexander F. Fitzpatrick, Christopher J. Chitre, Apurva S. St. Pierre, Celine L. Joyce, Elizabeth V. Maguire, Rachael J. McLeod, Africa M. Gonzales, Natalia M. Williams, April E. Morrow, Jonathan D. Robinson, Terry E. Flagel, Shelly B. Palmer, Abraham A. PLoS Genet Research Article Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (F(ST) > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted for population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies. Public Library of Science 2022-05-31 /pmc/articles/PMC9187121/ /pubmed/35639796 http://dx.doi.org/10.1371/journal.pgen.1010234 Text en © 2022 Gileta et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gileta, Alexander F. Fitzpatrick, Christopher J. Chitre, Apurva S. St. Pierre, Celine L. Joyce, Elizabeth V. Maguire, Rachael J. McLeod, Africa M. Gonzales, Natalia M. Williams, April E. Morrow, Jonathan D. Robinson, Terry E. Flagel, Shelly B. Palmer, Abraham A. Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title | Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title_full | Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title_fullStr | Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title_full_unstemmed | Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title_short | Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies |
title_sort | genetic characterization of outbred sprague dawley rats and utility for genome-wide association studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187121/ https://www.ncbi.nlm.nih.gov/pubmed/35639796 http://dx.doi.org/10.1371/journal.pgen.1010234 |
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